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Sample records for accelerated lung function

  1. Cumulative exposure to dust causes accelerated decline in lung function in tunnel workers

    PubMed Central

    Ulvestad, B; Bakke, B; Eduard, W; Kongerud, J; Lund, M

    2001-01-01

    most important risk factor for respiratory symptoms. The finding of accelerated decline in lung function in tunnel workers suggests that better control of exposures is needed.


Keywords: heavy construction; respirable dust; lung function PMID:11555688

  2. Antioxidants accelerate lung cancer progression in mice.

    PubMed

    Sayin, Volkan I; Ibrahim, Mohamed X; Larsson, Erik; Nilsson, Jonas A; Lindahl, Per; Bergo, Martin O

    2014-01-29

    Antioxidants are widely used to protect cells from damage induced by reactive oxygen species (ROS). The concept that antioxidants can help fight cancer is deeply rooted in the general population, promoted by the food supplement industry, and supported by some scientific studies. However, clinical trials have reported inconsistent results. We show that supplementing the diet with the antioxidants N-acetylcysteine (NAC) and vitamin E markedly increases tumor progression and reduces survival in mouse models of B-RAF- and K-RAS-induced lung cancer. RNA sequencing revealed that NAC and vitamin E, which are structurally unrelated, produce highly coordinated changes in tumor transcriptome profiles, dominated by reduced expression of endogenous antioxidant genes. NAC and vitamin E increase tumor cell proliferation by reducing ROS, DNA damage, and p53 expression in mouse and human lung tumor cells. Inactivation of p53 increases tumor growth to a similar degree as antioxidants and abolishes the antioxidant effect. Thus, antioxidants accelerate tumor growth by disrupting the ROS-p53 axis. Because somatic mutations in p53 occur late in tumor progression, antioxidants may accelerate the growth of early tumors or precancerous lesions in high-risk populations such as smokers and patients with chronic obstructive pulmonary disease who receive NAC to relieve mucus production.

  3. Functional imaging in lung cancer

    PubMed Central

    Harders, S W; Balyasnikowa, S; Fischer, B M

    2014-01-01

    Lung cancer represents an increasingly frequent cancer diagnosis worldwide. An increasing awareness on smoking cessation as an important mean to reduce lung cancer incidence and mortality, an increasing number of therapy options and a steady focus on early diagnosis and adequate staging have resulted in a modestly improved survival. For early diagnosis and precise staging, imaging, especially positron emission tomography combined with CT (PET/CT), plays an important role. Other functional imaging modalities such as dynamic contrast-enhanced CT (DCE-CT) and diffusion-weighted MR imaging (DW-MRI) have demonstrated promising results within this field. The purpose of this review is to provide the reader with a brief and balanced introduction to these three functional imaging modalities and their current or potential application in the care of patients with lung cancer. PMID:24289258

  4. Lung function in sisal ropemakers.

    PubMed Central

    Baker, M D; Irwig, L M; Johnston, J R; Turner, D M; Bezuidenhout, B N

    1979-01-01

    Lung function was measured by spirometry in 66 workers in a sisal ropemaking factory, and in their matched controls. The major atmospheric contaminant was the lubricant (or a component part thereof) used to soften the fibre. The concentration of airborne matter was generally less than 1 mug m--3. There was no difference in lung function between the two groups before the start of the working shift, that is, the mixture of softening lubricant and sisal caused no long-term effects. Although there was no change in lung function over the working shift in the group making sisal rope, the control group did show a significant increase in lung function over the same period. This suggests that an effect attributable to the lubricant and sisal dust did exist. In previous studies little mention has been made of the softeners used in the processing of sisal fibre. These additives may exert a significant effect on ventilatory capacity and may act in conjunction with sisal dust. PMID:500780

  5. Lung function in insulation workers.

    PubMed Central

    Clausen, J; Netterstrøm, B; Wolff, C

    1993-01-01

    To evaluate the effects of working with modern insulation materials (rock and glass wool), the members of the Copenhagen Union of Insulation Workers were invited to participate in a study based on a health examination that included lung function tests. Three hundred and forty men (74%) agreed to participate, and 166 bus drivers served as the control group. Age distribution, height, and smoking habits were similar in the two groups. Forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were used as tests for lung function. There were no differences in FVC between the study and control groups, but the insulation workers had significantly lower values of FEV1 (mean 2.51) compared with the controls (mean 3.4 1), independent of smoking habits. Six years before the present study, 114 of the insulation workers participated in a similar study, and eight years after the initial study, the lung function of 59 of the bus drivers was tested. The decline in FVC in insulation workers who smoked was significantly higher (7.7 cl/year) than in bus drivers who smoked (3.1 cl/year); the decline in FEV1 was significantly higher in insulation workers independent of smoking habits (17.0 cl/year v 2.9 cl/year). Self assessed former exposure to asbestos was not associated with lung function in insulation workers. The study concludes that working with modern insulation materials is associated with increased risk of developing obstructive lung disease. PMID:8457492

  6. What Are Lung Function Tests?

    MedlinePlus

    ... COPD How the Lungs Work Idiopathic Pulmonary Fibrosis Sarcoidosis Send a link to NHLBI to someone by ... the Lungs Work Idiopathic Pulmonary Fibrosis Oxygen Therapy Sarcoidosis Stress Testing Rate This Content: Updated: December 9, ...

  7. Lung function in pulmonary hypertension.

    PubMed

    Low, A T; Medford, A R L; Millar, A B; Tulloh, R M R

    2015-10-01

    Breathlessness is a common symptom in pulmonary hypertension (PH) and an important cause of morbidity. Though this has been attributed to the well described pulmonary vascular abnormalities and subsequent cardiac remodelling, changes in the airways of these patients have also been reported and may contribute to symptoms. Our understanding of these airway abnormalities is poor with conflicting findings in many studies. The present review evaluates these studies for the major PH groups. In addition we describe the role of cardiopulmonary exercise testing in the assessment of pulmonary arterial hypertension (PAH) by evaluating cardiopulmonary interaction during exercise. As yet, the reasons for the abnormalities in lung function are unclear, but potential causes and the possible role of inflammation are discussed. Future research is required to provide a better understanding of this to help improve the management of these patients.

  8. Functional lung imaging using hyperpolarized gas MRI.

    PubMed

    Fain, Sean B; Korosec, Frank R; Holmes, James H; O'Halloran, Rafael; Sorkness, Ronald L; Grist, Thomas M

    2007-05-01

    The noninvasive assessment of lung function using imaging is increasingly of interest for the study of lung diseases, including chronic obstructive pulmonary disease (COPD) and asthma. Hyperpolarized gas MRI (HP MRI) has demonstrated the ability to detect changes in ventilation, perfusion, and lung microstructure that appear to be associated with both normal lung development and disease progression. The physical characteristics of HP gases and their application to MRI are presented with an emphasis on current applications. Clinical investigations using HP MRI to study asthma, COPD, cystic fibrosis, pediatric chronic lung disease, and lung transplant are reviewed. Recent advances in polarization, pulse sequence development for imaging with Xe-129, and prototype low magnetic field systems dedicated to lung imaging are highlighted as areas of future development for this rapidly evolving technology.

  9. Regional lung function in asbestos workers.

    PubMed Central

    Seaton, D

    1977-01-01

    Regional lung function was measured using radioactive xenon-133 in a group of normal subjects and in two groups of asbestos workers. When compared with the normal group, patients with pulmonary asbestosis showed impaired ventilation of the lower zones. Subjects with calcified pleural plaques without radiological evidence of lung parenchymal fibrosis did not show this abnormality. PMID:841532

  10. Lung function in Pakistani wood workers.

    PubMed

    Meo, Sultan A

    2006-06-01

    The lung function impairment is the most common respiratory problem in industrial plants and their vicinity. Therefore, the purpose was to study the affects of wood dust and its duration of exposure on lung function. This was a matched cross-sectional study of Spirometry in 46 non-smoking wood workers with age range 20 - 60 years, who worked without the benefit of wood dust control ventilation or respiratory protective devices. Pulmonary function test was performed by using an electronic Spirometer. Significant reduction was observed in the mean values of Forced Vital Capacity (FVC), Forced Expiratory Volume in one second (FEV1), and Maximum Voluntary Ventilation (MVV) in wood workers relative to their matched controls. This impairment was increased with the duration of exposure to wood industries. It is concluded that lung function in wood workers is impaired and stratification of results shows a dose-response effect of years of wood dust exposure on lung function.

  11. Particulate air pollution and impaired lung function

    PubMed Central

    Paulin, Laura; Hansel, Nadia

    2016-01-01

    Air pollution is a leading cause of morbidity and mortality throughout the world, particularly in individuals with existing lung disease. Of the most common air pollutants, particulate matter (PM) is associated with an increased risk of exacerbations and respiratory symptoms in individuals with existing lung disease, and to a lesser extent, in those without known respiratory issues. The majority of published research has focused on the effects of PM exposures on symptoms and health care utilization. Fewer studies focus on the impact of PM on objective measurements of pulmonary function. This review will focus on the effects of PM exposure on objective measurements of lung function in both healthy individuals and those with existing lung disease. PMID:26962445

  12. Genetic Ancestry in Lung-Function Predictions

    PubMed Central

    Kumar, Rajesh; Seibold, Max A.; Aldrich, Melinda C.; Williams, L. Keoki; Reiner, Alex P.; Colangelo, Laura; Galanter, Joshua; Gignoux, Christopher; Hu, Donglei; Sen, Saunak; Choudhry, Shweta; Peterson, Edward L.; Rodriguez-Santana, Jose; Rodriguez-Cintron, William; Nalls, Michael A.; Leak, Tennille S.; O’Meara, Ellen; Meibohm, Bernd; Kritchevsky, Stephen B.; Li, Rongling; Harris, Tamara B.; Nickerson, Deborah A.; Fornage, Myriam; Enright, Paul; Ziv, Elad; Smith, Lewis J.; Liu, Kiang; Burchard, Esteban González

    2010-01-01

    BACKGROUND Self-identified race or ethnic group is used to determine normal reference standards in the prediction of pulmonary function. We conducted a study to determine whether the genetically determined percentage of African ancestry is associated with lung function and whether its use could improve predictions of lung function among persons who identified themselves as African American. METHODS We assessed the ancestry of 777 participants self-identified as African American in the Coronary Artery Risk Development in Young Adults (CARDIA) study and evaluated the relation between pulmonary function and ancestry by means of linear regression. We performed similar analyses of data for two independent cohorts of subjects identifying themselves as African American: 813 participants in the Health, Aging, and Body Composition (HABC) study and 579 participants in the Cardiovascular Health Study (CHS). We compared the fit of two types of models to lung-function measurements: models based on the covariates used in standard prediction equations and models incorporating ancestry. We also evaluated the effect of the ancestry-based models on the classification of disease severity in two asthma-study populations. RESULTS African ancestry was inversely related to forced expiratory volume in 1 second (FEV1) and forced vital capacity in the CARDIA cohort. These relations were also seen in the HABC and CHS cohorts. In predicting lung function, the ancestry-based model fit the data better than standard models. Ancestry-based models resulted in the reclassification of asthma severity (based on the percentage of the predicted FEV1) in 4 to 5% of participants. CONCLUSIONS Current predictive equations, which rely on self-identified race alone, may misestimate lung function among subjects who identify themselves as African American. Incorporating ancestry into normative equations may improve lung-function estimates and more accurately categorize disease severity. (Funded by the National

  13. Translating Lung Function Genome-Wide Association Study (GWAS) Findings: New Insights for Lung Biology.

    PubMed

    Kheirallah, A K; Miller, S; Hall, I P; Sayers, I

    2016-01-01

    Chronic respiratory diseases are a major cause of worldwide mortality and morbidity. Although hereditary severe deficiency of α1 antitrypsin (A1AD) has been established to cause emphysema, A1AD accounts for only ∼ 1% of Chronic Obstructive Pulmonary Disease (COPD) cases. Genome-wide association studies (GWAS) have been successful at detecting multiple loci harboring variants predicting the variation in lung function measures and risk of COPD. However, GWAS are incapable of distinguishing causal from noncausal variants. Several approaches can be used for functional translation of genetic findings. These approaches have the scope to identify underlying alleles and pathways that are important in lung function and COPD. Computational methods aim at effective functional variant prediction by combining experimentally generated regulatory information with associated region of the human genome. Classically, GWAS association follow-up concentrated on manipulation of a single gene. However association data has identified genetic variants in >50 loci predicting disease risk or lung function. Therefore there is a clear precedent for experiments that interrogate multiple candidate genes in parallel, which is now possible with genome editing technology. Gene expression profiling can be used for effective discovery of biological pathways underpinning gene function. This information may be used for informed decisions about cellular assays post genetic manipulation. Investigating respiratory phenotypes in human lung tissue and specific gene knockout mice is a valuable in vivo approach that can complement in vitro work. Herein, we review state-of-the-art in silico, in vivo, and in vitro approaches that may be used to accelerate functional translation of genetic findings.

  14. Divers' lung function: small airways disease?

    PubMed Central

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

    1990-01-01

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

  15. Lung function and bronchial reactivity in farmers.

    PubMed Central

    Iversen, M; Dahl, R; Jensen, E J; Korsgaard, J; Hallas, T

    1989-01-01

    The purpose of this study was to evaluate the prevalence and type of lung function disorders in Danish farmers. Three samples of farmers were drawn from a group of unselected farmers who had participated in an epidemiological study. Group I (47 persons) was a sample of the 8% of all farmers who had reported that they had asthma; group II (63 persons) was a sample of the 28% of farmers who had had wheezing, shortness of breath, or cough without phlegm; and group III (34 persons) a sample of the farmers (64% of the total) who had no asthma and no respiratory symptoms. The farmers with symptoms (groups I and II) had low mean levels of FEV1 and high values for residual volume, whereas the symptomless farmers had normal lung function and no airways obstruction. The proportion of farmers with an FEV1 below the 95% confidence limit for predicted values was 43% in group I and 23% in group II; there were none in group III. Bronchial hyperreactivity to histamine occurred in 96% of asthmatic farmers, 67% of farmers with wheezing or shortness of breath, and 59% of symptomless farmers. A low level of FEV1 was associated with the number of years in pig farming and bronchial hyperreactivity in group II but not group I or III. Most of the bronchial hyperreactivity was explained in the multiple regression analysis by a low FEV1, though this was significant only for farmers in group II. Thus farmers who reported asthma, wheezing, shortness of breath, or a dry cough in general had airways obstruction with an increased residual volume, whereas symptomless farmers had normal lung function. Severe bronchial hyperreactivity was mostly explained by a diagnosis of asthma and poor lung function, though some farmers with normal lung function and no respiratory symptoms had increased bronchial reactivity. PMID:2799744

  16. Hyperinsulinemia adversely affects lung structure and function.

    PubMed

    Singh, Suchita; Bodas, Manish; Bhatraju, Naveen K; Pattnaik, Bijay; Gheware, Atish; Parameswaran, Praveen Kolumam; Thompson, Michael; Freeman, Michelle; Mabalirajan, Ulaganathan; Gosens, Reinoud; Ghosh, Balaram; Pabelick, Christina; Linneberg, Allan; Prakash, Y S; Agrawal, Anurag

    2016-05-01

    There is limited knowledge regarding the consequences of hyperinsulinemia on the lung. Given the increasing prevalence of obesity, insulin resistance, and epidemiological associations with asthma, this is a critical lacuna, more so with inhaled insulin on the horizon. Here, we demonstrate that insulin can adversely affect respiratory health. Insulin treatment (1 μg/ml) significantly (P < 0.05) increased the proliferation of primary human airway smooth muscle (ASM) cells and induced collagen release. Additionally, ASM cells showed a significant increase in calcium response and mitochondrial respiration upon insulin exposure. Mice administered intranasal insulin showed increased collagen deposition in the lungs as well as a significant increase in airway hyperresponsiveness. PI3K/Akt mediated activation of β-catenin, a positive regulator of epithelial-mesenchymal transition and fibrosis, 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 of asthma-like phenotype.

  17. Accelerated cellular senescence phenotype of GAPDH-depleted human lung carcinoma cells

    SciTech Connect

    Phadke, Manali; Krynetskaia, Natalia; Mishra, Anurag; Krynetskiy, Evgeny

    2011-07-29

    Highlights: {yields} We examined the effect of glyceraldehyde 3-phosphate (GAPDH) depletion on proliferation of human carcinoma A549 cells. {yields} GAPDH depletion induces accelerated senescence in tumor cells via AMPK network, in the absence of DNA damage. {yields} Metabolic and genetic rescue experiments indicate that GAPDH has regulatory functions linking energy metabolism and cell cycle. {yields} Induction of senescence in LKB1-deficient lung cancer cells via GAPDH depletion suggests a novel strategy to control tumor cell proliferation. -- Abstract: Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is a pivotal glycolytic enzyme, and a signaling molecule which acts at the interface between stress factors and the cellular apoptotic machinery. Earlier, we found that knockdown of GAPDH in human carcinoma cell lines resulted in cell proliferation arrest and chemoresistance to S phase-specific cytotoxic agents. To elucidate the mechanism by which GAPDH depletion arrests cell proliferation, we examined the effect of GAPDH knockdown on human carcinoma cells A549. Our results show that GAPDH-depleted cells establish senescence phenotype, as revealed by proliferation arrest, changes in morphology, SA-{beta}-galactosidase staining, and more than 2-fold up-regulation of senescence-associated genes DEC1 and GLB1. Accelerated senescence following GAPDH depletion results from compromised glycolysis and energy crisis leading to the sustained AMPK activation via phosphorylation of {alpha} subunit at Thr172. Our findings demonstrate that GAPDH depletion switches human tumor cells to senescent phenotype via AMPK network, in the absence of DNA damage. Rescue experiments using metabolic and genetic models confirmed that GAPDH has important regulatory functions linking the energy metabolism and the cell cycle networks. Induction of senescence in LKB1-deficient non-small cell lung cancer cells via GAPDH depletion suggests a novel strategy to control tumor cell proliferation.

  18. Obesity and lung function: a systematic review

    PubMed Central

    Melo, Luciana Costa; da Silva, Maria Alayde Mendonça; Calles, Ana Carolina do Nascimento

    2014-01-01

    ABSTRACT Obesity is a chronic disease characterized by the excessive accumulation of body fat that is harmful to the individuals. Respiratory disorders are among the comorbidities associated with obesity. This study had the objective of investigating the alterations in respiratory function that affect obese individuals. A systematic review was performed, by selecting publications in the science databases MEDLINE and LILACS, using PubMed and SciELO. The articles that assessed pulmonary function by plethysmography and/or spirometry in obese individuals aged under 18 years were included. The results demonstrated that the obese individuals presented with a reduction in lung volume and capacity as compared to healthy individuals. Reduction of total lung capacity and reduction of forced vital capacity, accompanied by reduction of the forced expiratory volume after one second were the most representative findings in the samples. The articles analyzed proved the presence of a restrictive respiratory pattern associated with obesity. PMID:24728258

  19. Lung Function Monitoring; A Randomized Agreement Study

    PubMed Central

    Berntsen, Sveinung; Stølevik, Solvor B.; Mowinckel, Petter; Nystad, Wenche; Stensrud, Trine

    2016-01-01

    Objective: To determine the agreement between devices and repeatability within devices of the forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), peak expiratory flow (PEF) and forced expiratory flow at 50% of FVC (FEF50) values measured using the four spirometers included in the study. Methods: 50 (24 women) participants (20-64 years of age) completed maximum forced expiratory flow manoeuvres and measurements were performed using the following devices: MasterScreen, SensorMedics, Oxycon Pro and SpiroUSB. The order of the instruments tested was randomized and blinded for both the participants and the technicians. Re-testing was conducted on a following day within 72 hours at the same time of the day. Results: The devices which obtained the most comparable values for all lung function variables were SensorMedics and Oxycon Pro, and MasterScreen and SpiroUSB. For FEV1, mean difference was 0.04 L (95% confidence interval; -0.05, 0.14) and 0.00 L (-0.06, 0.06), respectively. When using the criterion of FVC and FEV1 ≤ 0.150 L for acceptable repeatability, 67% of the comparisons of the measured lung function values obtained by the four devices were acceptable. Overall, Oxycon Pro obtained most frequently values of the lung function variables with highest precision as indicated by the coefficients of repeatability (CR), followed by MasterScreen, SensorMedics and SpiroUSB (e.g. min-max CR for FEV1; 0.27-0.46). Conclusion: The present study confirms that measurements obtained by the same device at different times can be compared; however, measured lung function values may differ depending on spirometers used. PMID:27583055

  20. Accelerating functional verification of an integrated circuit

    SciTech Connect

    Deindl, Michael; Ruedinger, Jeffrey Joseph; Zoellin, Christian G.

    2015-10-27

    Illustrative embodiments include a method, system, and computer program product for accelerating functional verification in simulation testing of an integrated circuit (IC). Using a processor and a memory, a serial operation is replaced with a direct register access operation, wherein the serial operation is configured to perform bit shifting operation using a register in a simulation of the IC. The serial operation is blocked from manipulating the register in the simulation of the IC. Using the register in the simulation of the IC, the direct register access operation is performed in place of the serial operation.

  1. Lung function after acute chlorine exposure

    SciTech Connect

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

    1986-12-01

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

  2. Pten Inactivation Accelerates Oncogenic K-ras-Initiated Tumorigenesis in a Mouse Model of Lung Cancer

    PubMed Central

    Iwanaga, Kentaro; Yang, Yanan; Raso, Maria Gabriela; Ma, Lijiang; Hanna, Amy E.; Thilaganathan, Nishan; Moghaddam, Seyed; Evans, Christopher M.; Li, Huaiguang; Cai, Wei-Wen; Sato, Mitsuo; Minna, John D.; Wu, Hong; Creighton, Chad J.; Demayo, Francesco J.; Wistuba, Ignacio I.; Kurie, Jonathan M.

    2009-01-01

    Phosphatase and tensin homologue deleted from chromosome 10 (Pten) is expressed aberrantly in non-small cell lung cancer cells, but the role of Pten in lung neoplasia has not been fully elucidated. In this study, we used a genetic approach to inactivate Pten in the bronchial epithelium of mice. Although, by itself, Pten inactivation had no discernible effect on bronchial epithelial histology, it accelerated lung tumorigenesis initiated by oncogenic K-ras, causing more rapid lethality than that induced by oncogenic K-ras alone (8 weeks versus 24 weeks of median duration of survival, respectively). Lung tumors arose in K-ras mutant, Pten-deficient mice that rapidly obstructed bronchial lumina and replaced alveolar spaces. Relative to K-ras mutant tumors, the K-ras mutant, Pten-deficient tumors exhibited more advanced histologic severity and more prominent inflammation and vascularity. Thus, Pten inactivation cooperated with oncogenic K-ras in promoting lung tumorigenesis. PMID:18281487

  3. Lung cancer tissue diagnosis in poor lung function: addressing the ongoing percutaneous lung biopsy FEV1 paradox using Heimlich valve.

    PubMed

    Abdullah, R; Tavare, A N; Creamer, A; Creer, D; Vancheeswaran, R; Hare, S S

    2016-08-01

    Many centres continue to decline percutaneous lung biopsy (PLB) in patients with poor lung function (particularly FEV1 <1 L) due to the theoretically increased risk of pneumothorax. This practice limits access to novel lung cancer therapies and minimally invasive surgical techniques. Our retrospective single-centre analysis of 212 patients undergoing PLB, all performed prospectively and blinded to lung function, demonstrates that using ambulatory Heimlich valve chest drain (HVCD) to treat significant postbiopsy pneumothorax facilitates safe, diagnostic, early discharge lung biopsy irrespective of lung function with neither FEV1 <1 L nor transfer coefficient for carbon monoxide (TLCO) <40% predicted shown to be independent predictors of HVCD insertion or pneumothorax outcomes. Incorporating ambulatory HVCD into standard PLB practice thereby elegantly bridges the gap that currently exists between tissue diagnosis in patients with poor lung function and the advanced therapeutic options available for this cohort.

  4. Ethnic Differences in Adolescent Lung Function

    PubMed Central

    Whitrow, Melissa J.; Harding, Seeromanie

    2008-01-01

    Rationale: The relative contribution of body proportion and social exposures to ethnic differences in lung function has not previously been reported in the United Kingdom. Objectives: To examine ethnic differences in lung function in relation to anthropometry and social and psychosocial factors in early adolescence. Methods: The subjects of this study were 3,924 pupils aged 11 to 13 years, of whom 80% were ethnic minorities with satisfactory lung function measures. Data were collected on economic disadvantage, psychological well-being, tobacco exposure, height, FEV1, and FVC. Measurements and Main Results: The lowest FEV1 was observed for Black Caribbean/African children after adjusting for standing height (SH) (white boys: 2.475 L; 95% confidence interval [CI], 2.442–2.509; white girls: 2.449 L; 95% CI, 2.464–2.535]; Black Caribbean boys: −14% [95% CI, −16 to −12]; Black Caribbean girls: −13% [95% CI, −16 to −11]; Black African boys: −15% [95% CI, −17 to −13]; Black African girls: −17% [95% CI, −19 to −14]; Indian boys: −13% [95% CI, −16 to −11]; Indian girls: −11% [95% CI, −14 to −8]; Pakistani/Bangladeshi boys: −7% [95% CI, −9 to −5]; Pakistani/Bangladeshi girls: −9% [95% CI, −11 to −6]). Adjustment for upper body segment instead of SH achieved a further reduction in ethnic differences of 41 to 51% for children of Black African origin and 26 to 39% for the other groups. Overcrowding (boys) and poor psychological well-being (boys and girls) were independent correlates of FEV1, explaining up to a further 10% of ethnic differences. Similar patterns were observed for FVC. Social exposures were also related to height components. Conclusions: Differences in upper body segment explained more of the ethnic differences in lung function than SH, particularly among Black Caribbeans/African subjects. Social correlates had a smaller but significant impact. Future research needs to consider how differential development of

  5. Functional imaging of the lungs with gas agents.

    PubMed

    Kruger, Stanley J; Nagle, Scott K; Couch, Marcus J; Ohno, Yoshiharu; Albert, Mitchell; Fain, Sean B

    2016-02-01

    This review focuses on the state-of-the-art of the three major classes of gas contrast agents used in magnetic resonance imaging (MRI)-hyperpolarized (HP) gas, molecular oxygen, and fluorinated gas--and their application to clinical pulmonary research. During the past several years there has been accelerated development of pulmonary MRI. This has been driven in part by concerns regarding ionizing radiation using multidetector computed tomography (CT). However, MRI also offers capabilities for fast multispectral and functional imaging using gas agents that are not technically feasible with CT. Recent improvements in gradient performance and radial acquisition methods using ultrashort echo time (UTE) have contributed to advances in these functional pulmonary MRI techniques. The relative strengths and weaknesses of the main functional imaging methods and gas agents are compared and applications to measures of ventilation, diffusion, and gas exchange are presented. Functional lung MRI methods using these gas agents are improving our understanding of a wide range of chronic lung diseases, including chronic obstructive pulmonary disease, asthma, and cystic fibrosis in both adults and children.

  6. Determination of higher order accelerations by a functional method

    NASA Astrophysics Data System (ADS)

    Tudosie, C.

    A functional method is developed for the simultaneous determination of all the linear accelerations which exist in the differential equation of a material system dynamics. The method introduces variable angular accelerations of different orders, called direct connection functions, which allow the passing from a linear acceleration of a certain order to that of a higher order. Feedback functions are also introduced which allow the passing from a linear acceleration of a certain order to that of lower orders. This method is applicable to accelerations which occur when passenger trains move rapidly around a curve and at the vertical vibrations of trucks and tractors.

  7. Lung transplantation in adults and children: putting lung function into perspective.

    PubMed

    Thompson, Bruce Robert; Westall, Glen Philip; Paraskeva, Miranda; Snell, Gregory Ian

    2014-11-01

    The number of lung transplants performed globally continues to increase year after year. Despite this growing experience, long-term outcomes following lung transplantation continue to fall far short of that described in other solid-organ transplant settings. Chronic lung allograft dysfunction (CLAD) remains common and is the end result of exposure to a multitude of potentially injurious insults that include alloreactivity and infection among others. Central to any description of the clinical performance of the transplanted lung is an assessment of its physiology by pulmonary function testing. Spirometry and the evaluation of forced expiratory volume in 1 s and forced vital capacity, remain core indices that are measured as part of routine clinical follow-up. Spirometry, while reproducible in detecting lung allograft dysfunction, lacks specificity in differentiating the different complications of lung transplantation such as rejection, infection and bronchiolitis obliterans. However, interpretation of spirometry is central to defining the different 'chronic rejection' phenotypes. It is becoming apparent that the maximal lung function achieved following transplantation, as measured by spirometry, is influenced by a number of donor and recipient factors as well as the type of surgery performed (single vs double vs lobar lung transplant). In this review, we discuss the wide range of variables that need to be considered when interpreting lung function testing in lung transplant recipients. Finally, we review a number of novel measurements of pulmonary function that may in the future serve as better biomarkers to detect and diagnose the cause of the failing lung allograft.

  8. Systemic inflammation and lung function: A longitudinal analysis

    PubMed Central

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

    2016-01-01

    Background 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. Methods 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. Results 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. Conclusions 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. PMID:26733230

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

    PubMed Central

    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

  10. GPU accelerated dynamic functional connectivity analysis for functional MRI data.

    PubMed

    Akgün, Devrim; Sakoğlu, Ünal; Esquivel, Johnny; Adinoff, Bryon; Mete, Mutlu

    2015-07-01

    Recent advances in multi-core processors and graphics card based computational technologies have paved the way for an improved and dynamic utilization of parallel computing techniques. Numerous applications have been implemented for the acceleration of computationally-intensive problems in various computational science fields including bioinformatics, in which big data problems are prevalent. In neuroimaging, dynamic functional connectivity (DFC) analysis is a computationally demanding method used to investigate dynamic functional interactions among different brain regions or networks identified with functional magnetic resonance imaging (fMRI) data. In this study, we implemented and analyzed a parallel DFC algorithm based on thread-based and block-based approaches. The thread-based approach was designed to parallelize DFC computations and was implemented in both Open Multi-Processing (OpenMP) and Compute Unified Device Architecture (CUDA) programming platforms. Another approach developed in this study to better utilize CUDA architecture is the block-based approach, where parallelization involves smaller parts of fMRI time-courses obtained by sliding-windows. Experimental results showed that the proposed parallel design solutions enabled by the GPUs significantly reduce the computation time for DFC analysis. Multicore implementation using OpenMP on 8-core processor provides up to 7.7× speed-up. GPU implementation using CUDA yielded substantial accelerations ranging from 18.5× to 157× speed-up once thread-based and block-based approaches were combined in the analysis. Proposed parallel programming solutions showed that multi-core processor and CUDA-supported GPU implementations accelerated the DFC analyses significantly. Developed algorithms make the DFC analyses more practical for multi-subject studies with more dynamic analyses.

  11. Cross sectional study on lung function of coke oven workers: a lung function surveillance system from 1978 to 1990

    PubMed Central

    Wu, J; Kreis, I; Griffiths, D; Darling, C

    2002-01-01

    Aims: To determine the association between lung function of coke oven workers and exposure to coke oven emissions. Methods: Lung function data and detailed work histories for workers in recovery coke ovens of a steelworks were extracted from a lung function surveillance system. Multiple regressions were employed to determine significant predictors for lung function indices. The first sets of lung function tests for 613 new starters were pooled to assess the selection bias. The last sets of lung function tests for 834 subjects with one or more year of coke oven history were pooled to assess determinants of lung function. Results: Selection bias associated with the recruitment process was not observed among the exposure groups. For subjects with a history of one or more years of coke oven work, each year of working in the most exposed "operation" position was associated with reductions in FEV1 of around 9 ml (p = 0.006, 95% CI: 3 ml to 16 ml) and in FVC of around 12 ml (p = 0.002, 95% CI: 4 ml to 19 ml). Negative effects of smoking on lung function were also observed. Conclusions: Exposure to coke oven emissions was found to be associated with lower FEV1 and FVC. Effects of work exposure on lung function are similar to those found in other studies. PMID:12468747

  12. Accelerated deflation promotes homogeneous airspace liquid distribution in the edematous lung.

    PubMed

    Wu, You; Nguyen, Tam L; Perlman, Carrie E

    2016-12-15

    Edematous lungs contain regions with heterogeneous alveolar flooding. Liquid is trapped in flooded alveoli by a pressure barrier--higher liquid pressure at the border than in the center of flooded alveoli--that is proportional to surface tension, T Stress is concentrated between aerated and flooded alveoli, to a degree proportional to T Mechanical ventilation, by cyclically increasing T, injuriously exacerbates stress concentrations. Overcoming the pressure barrier to redistribute liquid more homogeneously between alveoli should reduce stress concentration prevalence and ventilation injury. In isolated rat lungs, we test whether accelerated deflation can overcome the pressure barrier and catapult liquid out of flooded alveoli. We generate a local edema model with normal T by microinfusing liquid into surface alveoli. We generate a global edema model with high T by establishing hydrostatic edema, which does not alter T, and then gently ventilating the edematous lungs, which increases T at 15 cmH2O transpulmonary pressure by 52%. Thus ventilation of globally edematous lungs increases T, which should increase stress concentrations and, with positive feedback, cause escalating ventilation injury. In the local model, when the pressure barrier is moderate, accelerated deflation causes liquid to escape from flooded alveoli and redistribute more equitably. Flooding heterogeneity tends to decrease. In the global model, accelerated deflation causes liquid escape, but--due to elevated T--the liquid jumps to nearby, aerated alveoli. Flooding heterogeneity is unaltered. In pulmonary edema with normal T, early ventilation with accelerated deflation might reduce the positive feedback mechanism through which ventilation injury increases over time.

  13. In Vivo Lung Morphometry with Accelerated Hyperpolarized 3He Diffusion MRI: A Preliminary Study

    PubMed Central

    Chang, Yulin V.; Quirk, James D.; Yablonskiy, Dmitriy A.

    2014-01-01

    Purpose Parallel imaging can be used to reduce imaging time and to increase the spatial coverage in hyperpolarized gas MRI of the lung. In this proof-of-concept study we investigate the effects of parallel imaging on the morphometric measurement of lung microstructure using diffusion MRI with hyperpolarized 3He. Methods Fully sampled and under-sampled multi-b diffusion data were acquired from human subjects using an 8-channel 3He receive coil. A parallel imaging reconstruction technique (GRAPPA) was used to reconstruct under-sampled k-space data. The morphometric results of the GRAPPA-reconstructed data were compared with the results of fully sampled data for three types of subjects: healthy volunteers, mild, and moderate COPD patients. Results Morphometric measurements varied only slightly at mild acceleration factors. The results were largely well preserved compared to fully sampled data for different lung conditions. Conclusion Parallel imaging, given sufficient signal-to-noise ratio, provides a reliable means to accelerate hyperpolarized-gas MRI with no significant difference in the measurement of lung morphometry from the fully sampled images. GRAPPA is a promising technique to significantly reduce imaging time and/or to improve the spatial coverage for the morphometric measurement with hyperpolarized gases. PMID:24799044

  14. Linking lung function and inflammatory responses in ventilator-induced lung injury.

    PubMed

    Cannizzaro, Vincenzo; Hantos, Zoltan; Sly, Peter D; Zosky, Graeme R

    2011-01-01

    Despite decades of research, the mechanisms of ventilator-induced lung injury are poorly understood. We used strain-dependent responses to mechanical ventilation in mice to identify associations between mechanical and inflammatory responses in the lung. BALB/c, C57BL/6, and 129/Sv mice were ventilated using a protective [low tidal volume and moderate positive end-expiratory pressure (PEEP) and recruitment maneuvers] or injurious (high tidal volume and zero PEEP) ventilation strategy. Lung mechanics and lung volume were monitored using the forced oscillation technique and plethysmography, respectively. Inflammation was assessed by measuring numbers of inflammatory cells, cytokine (IL-6, IL-1β, and TNF-α) levels, and protein content of the BAL. Principal components factor analysis was used to identify independent associations between lung function and inflammation. Mechanical and inflammatory responses in the lung were dependent on ventilation strategy and mouse strain. Three factors were identified linking 1) pulmonary edema, protein leak, and macrophages, 2) atelectasis, IL-6, and TNF-α, and 3) IL-1β and neutrophils, which were independent of responses in lung mechanics. This approach has allowed us to identify specific inflammatory responses that are independently associated with overstretch of the lung parenchyma and loss of lung volume. These data provide critical insight into the mechanical responses in the lung that drive local inflammation in ventilator-induced lung injury and the basis for future mechanistic studies in this field.

  15. Predicting Structure-Function Relations and Survival following Surgical and Bronchoscopic Lung Volume Reduction Treatment of Emphysema

    PubMed Central

    Mondoñedo, Jarred R.

    2017-01-01

    Lung volume reduction surgery (LVRS) and bronchoscopic lung volume reduction (bLVR) are palliative treatments aimed at reducing hyperinflation in advanced emphysema. Previous work has evaluated functional improvements and survival advantage for these techniques, although their effects on the micromechanical environment in the lung have yet to be determined. Here, we introduce a computational model to simulate a force-based destruction of elastic networks representing emphysema progression, which we use to track the response to lung volume reduction via LVRS and bLVR. We find that (1) LVRS efficacy can be predicted based on pre-surgical network structure; (2) macroscopic functional improvements following bLVR are related to microscopic changes in mechanical force heterogeneity; and (3) both techniques improve aspects of survival and quality of life influenced by lung compliance, albeit while accelerating disease progression. Our model predictions yield unique insights into the microscopic origins underlying emphysema progression before and after lung volume reduction. PMID:28182686

  16. Predicting Structure-Function Relations and Survival following Surgical and Bronchoscopic Lung Volume Reduction Treatment of Emphysema.

    PubMed

    Mondoñedo, Jarred R; Suki, Béla

    2017-02-01

    Lung volume reduction surgery (LVRS) and bronchoscopic lung volume reduction (bLVR) are palliative treatments aimed at reducing hyperinflation in advanced emphysema. Previous work has evaluated functional improvements and survival advantage for these techniques, although their effects on the micromechanical environment in the lung have yet to be determined. Here, we introduce a computational model to simulate a force-based destruction of elastic networks representing emphysema progression, which we use to track the response to lung volume reduction via LVRS and bLVR. We find that (1) LVRS efficacy can be predicted based on pre-surgical network structure; (2) macroscopic functional improvements following bLVR are related to microscopic changes in mechanical force heterogeneity; and (3) both techniques improve aspects of survival and quality of life influenced by lung compliance, albeit while accelerating disease progression. Our model predictions yield unique insights into the microscopic origins underlying emphysema progression before and after lung volume reduction.

  17. [Portable lung function parameters testing system based on DSP].

    PubMed

    Guo, Zhanshe; Yuan, Minzhong; Zhou, Hui

    2012-11-01

    Lung function monitoring is a critical technique for clinical medicine. Currently, the lung function testing devices used in our domestic hospitals are both expensive and bulky. A portable and accurate lung function parameters testing system is highly desired and is proposed in this paper. The hardware of the system is based on DSP technology. The breathing passage is designed with an aim suitable for the breathe and signal detection. We use the direct detection method to detect the gas flow, the breathing passage pressure and the breathing time. Thanks to the powerful data processing ability and the high operation speed of the DSP, breathing signals can be easily analyzed. Thus, several lung function parameters of clinical significance can be obtained. Experiments show that the accuracy of the system is better than 3%, and could meet the demand of the lung function testing.

  18. Pulmonary acceleration time to optimize the timing of lung transplant in cystic fibrosis.

    PubMed

    Damy, Thibaud; Burgel, Pierre-Régis; Pepin, Jean-Louis; Boelle, Pierre-Yves; Cracowski, Claire; Murris-Espin, Marlène; Nove-Josserand, Raphaele; Stremler, Nathalie; Simon, Tabassome; Adnot, Serge; Fauroux, Brigitte

    2012-01-01

    Pulmonary hypertension (PH) may affect survival in cystic fibrosis (CF) and can be assessed on echocardiographic measurement of the pulmonary acceleration time (PAT). The study aimed at evaluating PAT as a tool to optimize timing of lung transplant in CF patients. Prospective multicenter longitudinal study of patients with forced expiratory volume in 1 second (FEV1) ≤60% predicted. Echocardiography, spirometry and nocturnal oximetry were obtained as part of the routine evaluation. We included 67 patients (mean FEV1 42±12% predicted), among whom 8 underwent lung transplantation during the mean follow-up of 19±6 months. No patients died. PAT was determined in all patients and correlated negatively with systolic pulmonary artery pressure (sPAP, r=-0.36, P=0.01). Patients in the lowest PAT tertile (<101 ms) had lower FEV1 and worse nocturnal oxygen saturation, and they were more often on the lung transplant waiting list compared to patients in the other tertiles. Kaplan-Meier curves showed a shorter time to lung transplantation in the lowest PAT tertile (P<0.001) but not in patients with sPAP>35 mmHg. By multivariate analysis, FEV(1)and nocturnal desaturation were the main determinants of reduced PAT. A PAT<101 ms reduction is a promising tool for timing of lung transplantation in CF.

  19. Pulmonary acceleration time to optimize the timing of lung transplant in cystic fibrosis

    PubMed Central

    Damy, Thibaud; Burgel, Pierre-Régis; Pepin, Jean-Louis; Boelle, Pierre-Yves; Cracowski, Claire; Murris-Espin, Marlène; Nove-Josserand, Raphaele; Stremler, Nathalie; Simon, Tabassome; Adnot, Serge; Fauroux, Brigitte

    2012-01-01

    Pulmonary hypertension (PH) may affect survival in cystic fibrosis (CF) and can be assessed on echocardiographic measurement of the pulmonary acceleration time (PAT). The study aimed at evaluating PAT as a tool to optimize timing of lung transplant in CF patients. Prospective multicenter longitudinal study of patients with forced expiratory volume in 1 second (FEV1) ≤60% predicted. Echocardiography, spirometry and nocturnal oximetry were obtained as part of the routine evaluation. We included 67 patients (mean FEV1 42±12% predicted), among whom 8 underwent lung transplantation during the mean follow-up of 19±6 months. No patients died. PAT was determined in all patients and correlated negatively with systolic pulmonary artery pressure (sPAP, r=–0.36, P=0.01). Patients in the lowest PAT tertile (<101 ms) had lower FEV1 and worse nocturnal oxygen saturation, and they were more often on the lung transplant waiting list compared to patients in the other tertiles. Kaplan–Meier curves showed a shorter time to lung transplantation in the lowest PAT tertile (P<0.001) but not in patients with sPAP>35 mmHg. By multivariate analysis, FEV1and nocturnal desaturation were the main determinants of reduced PAT. A PAT<101 ms reduction is a promising tool for timing of lung transplantation in CF. PMID:22558523

  20. Metabolic Functions of the Lung, Disorders and Associated Pathologies

    PubMed Central

    Alvarado, Alcibey; Arce, Isabel

    2016-01-01

    The primary function of the lungs is gas exchange. Approximately 400 million years ago, the Earth’s atmosphere gained enough oxygen in the gas phase for the animals that emerged from the sea to breathe air. The first lungs were merely primitive air sacs with a few vessels in the walls that served as accessory organs of gas exchange to supplement the gills. Eons later, as animals grew accustomed to a solely terrestrial life, the lungs became highly compartmentalized to provide the vast air-blood surface necessary for O2 uptake and CO2 elimination, and a respiratory control system was developed to regulate breathing in accordance with metabolic demands and other needs. With the evolution and phylogenetic development, lungs were taking a variety of other specialized functions to maintain homeostasis, which we will call the non-respiratory functions of the lung and that often, and by mistake, are believed to have little or no connection with the replacement gas. In this review, we focus on the metabolic functions of the lung, perhaps the least known, and mainly, in the lipid metabolism and blood-adult lung vascular endothelium interaction. When these functions are altered, respiratory disorders or diseases appear, which are discussed concisely, emphasizing how they impact the most important function of the lungs: external respiration. PMID:27635172

  1. Metabolic Functions of the Lung, Disorders and Associated Pathologies.

    PubMed

    Alvarado, Alcibey; Arce, Isabel

    2016-10-01

    The primary function of the lungs is gas exchange. Approximately 400 million years ago, the Earth's atmosphere gained enough oxygen in the gas phase for the animals that emerged from the sea to breathe air. The first lungs were merely primitive air sacs with a few vessels in the walls that served as accessory organs of gas exchange to supplement the gills. Eons later, as animals grew accustomed to a solely terrestrial life, the lungs became highly compartmentalized to provide the vast air-blood surface necessary for O2 uptake and CO2 elimination, and a respiratory control system was developed to regulate breathing in accordance with metabolic demands and other needs. With the evolution and phylogenetic development, lungs were taking a variety of other specialized functions to maintain homeostasis, which we will call the non-respiratory functions of the lung and that often, and by mistake, are believed to have little or no connection with the replacement gas. In this review, we focus on the metabolic functions of the lung, perhaps the least known, and mainly, in the lipid metabolism and blood-adult lung vascular endothelium interaction. When these functions are altered, respiratory disorders or diseases appear, which are discussed concisely, emphasizing how they impact the most important function of the lungs: external respiration.

  2. Tiny Device Mimics Human Lung Function

    SciTech Connect

    McDonald, Rebecca; Harris, Jennifer; Nath, Pulak

    2016-04-25

    Scientists at Los Alamos National Laboratory are developing a miniature, tissue-engineered artificial lung that mimics the response of the human lung to drugs, toxins and other agents. “We breathe in and out thousands of times every day. And while we have control over what we eat or drink, we don’t always have control over what we breathe in,” said Jennifer Harris of Biosecurity and Public Health at Los Alamos, "and so we’re making this miniature lung to be able to test on actual human cells whether something in the environment, or a drug, is toxic or harmful to us." Nicknamed “PuLMo” for Pulmonary Lung Model (Pulmo is also the Latin word for "lung")the device consists of two major parts, the bronchiolar unit and the alveolar unit—just like the human lung. The units are primarily made from various polymers and are connected by a microfluidic “circuit board” that manages fluid and air flow. “When we build our lung, we not only take into account the aspects of different cell types, the tissues that are involved, we also take into account that a lung is supposed to breathe, so PuLMo actually breathes,” said Pulak Nath of Applied Modern Physics, who leads engineering efforts for the project. The most exciting application of PuLMo is a potentially revolutionary improvement in the reliability of drug-toxicity assessments and the prediction of new pharmaceutical success in humans, according to Harris. The PuLMo may also be designed to mimic lung disease conditions, such as Chronic Obstructive Pulmonary Disease (COPD) and asthma, and may be used to study lung air-flow dynamics to better understand the mechanisms of toxins and drug delivery and the effects of smoking, particularly the less-understood effects of e-cigarettes.

  3. Pericardial Fat Is Associated With Impaired Lung Function and a Restrictive Lung Pattern in Adults

    PubMed Central

    Liu, Jiankang; Bidulescu, Aurelian; Burchfiel, Cecil M.; Taylor, Herman A.; Petrini, Marcy F.

    2011-01-01

    Background: Impaired lung function has been linked to obesity and systemic inflammation. Pericardial fat has been shown to be associated with anomalies in cardiac structure, function, and atherosclerosis. We hypothesized that pericardial fat may have a similar role in the impairment of lung function. Methods: Cross-sectional associations of pericardial fat volumes, quantified by multidetector CT scan, with FEV1 and FVC assessed by spirometry, were investigated in 1,293 participants (54.5 ± 10.8 years; 66.4% women) in the Jackson Heart Study. We also examined whether these associations were independent of visceral adipose tissue (VAT). Results: Pericardial fat was associated with impaired lung function after multivariable adjustment, but these associations generally did not remain after adjustment for VAT. An exception was the FEV1/FVC ratio. Higher pericardial fat volumes were associated with higher odds of a restrictive lung pattern and lower odds of airway obstruction. Participants in the highest quartile had the highest odds of a restrictive lung pattern (OR, 1.85; 95% CI, 1.22-2.79, compared with quartile 1), even after adjustment for VAT. The odds of obstruction decreased across increasing quartiles of pericardial fat. These relationships were generally graded, suggesting dose-response trends. Conclusions: Pericardial fat is generally associated with lower lung function and independently associated with a restrictive lung pattern in middle-aged and elderly adults. Further research is needed to fully understand the mechanisms through which pericardial fat contributes to pulmonary anomalies. PMID:21737489

  4. Dicer function is essential for lung epithelium morphogenesis.

    PubMed

    Harris, Kelley S; Zhang, Zhen; McManus, Michael T; Harfe, Brian D; Sun, Xin

    2006-02-14

    DICER is a key enzyme that processes microRNA and small interfering RNA precursors into their short mature forms, enabling them to regulate gene expression. Only a single Dicer gene exists in the mouse genome, and it is broadly expressed in developing tissues. Dicer-null mutants die before gastrulation. Therefore, to study Dicer function in the later event of lung formation, we inactivated it in the mouse lung epithelium using a Dicer conditional allele and the Sonic Hedgehogcre (Shhcre) allele. Branching arrests in these mutant lungs, although epithelial growth continues in distal domains that are expanded compared with normal samples. These defects result in a few large epithelial pouches in the mutant lung instead of numerous fine branches present in a normal lung. Significantly, the initial phenotypes are apparent before an increase in epithelial cell death is observed, leading us to propose that Dicer plays a specific role in regulating lung epithelial morphogenesis independent of its requirement in cell survival. In addition, we found that the expression of Fgf10, a key gene involved in lung development, is up-regulated and expanded in the mesenchyme of Dicer mutant lungs. Previous studies support the hypothesis that precise localization of FGF10 in discrete sites of the lung mesenchyme serves as a chemoattractant for the outgrowth of epithelial branches. The aberrant Fgf10 expression may contribute to the Dicer morphological defects. However, the mechanism by which DICER functions in the epithelium to influence Fgf10 expression in the mesenchyme remains unknown.

  5. Associations of dairy intake with CT lung density and lung function

    PubMed Central

    Jiang, Rui; Jacobs, David R.; He, Ka; Hoffman, Eric; Hankinson, John; Nettleton, Jennifer A.; Barr, R. Graham

    2013-01-01

    Objective Dairy products contain vitamin D and other nutrients that may be beneficial for lung function, but are also high in fats that may have mixed effects on lung function. However, the overall associations of dairy intake with lung density and lung function have not been studied. Methods We examined the cross-sectional relations between dairy intake and CT lung density and lung function in the Multi-Ethnic Study of Atherosclerosis (MESA). Total, low-fat and high-fat dairy intakes were quantified from food frequency questionnaire responses of men and women, aged 45–84 years, free of clinical cardiovascular disease. The MESA-Lung Study assessed CT lung density from cardiac CT imaging and prebronchodilator spirometry among 3,965 MESA participants. Results Total dairy intake was inversely associated with apical-basilar difference in percent emphysema and positively associated with FVC (the multivariate-adjusted mean difference between the highest and the lowest quintile of total dairy intake was −0.92 (p for trend=0.04) for apical-basilar difference in percent emphysema and 72.0 mL (p=0.01) for FVC). Greater low-fat dairy intake was associated with higher alpha (higher alpha values indicate less emphysema) and lower apical-basilar difference in percent emphysema (corresponding differences in alpha and apical-basilar difference in percent emphysema were 0.04 (p=0.02) and −0.98 (p=0.01) for low-fat dairy intake, respectively). High-fat dairy intake was not associated with lung density measures. Greater low- or high-fat dairy intake was not associated with higher FEV1, FVC and FEV1/FVC. Conclusions Higher low-fat dairy intake but not high-fat dairy intake was associated with moderately improved CT lung density. PMID:21504976

  6. PREOPERATIVE PREDICTION OF LUNG FUNCTION IN PNEUMONECTOMY BY SPIROMETRY AND LUNG PERFUSION SCINTIGRAPHY

    PubMed Central

    Cukic, Vesna

    2012-01-01

    Introduction: Nowadays an increasing number of lung resections are being done because of the rising prevalence of lung cancer that occurs mainly in patients with limited lung function, what is caused by common etiologic factor - smoking cigarettes. Loss of lung tissue in such patients can worsen much the postoperative pulmonary function. So it is necessary to asses the postoperative pulmonary function especially after maximal resection, i.e. pneumonectomy. Objective: To check over the accuracy of preoperative prognosis of postoperative lung function after pneumonectomy using spirometry and lung perfusion scinigraphy. Material and methods: The study was done on 17 patients operated at the Clinic for thoracic surgery, who were treated previously at the Clinic for Pulmonary Diseases “Podhrastovi” in the period from 01. 12. 2008. to 01. 06. 2011. Postoperative pulmonary function expressed as ppoFEV1 (predicted postoperative forced expiratory volume in one second) was prognosticated preoperatively using spirometry, i.e.. simple calculation according to the number of the pulmonary segments to be removed and perfusion lung scintigraphy. Results: There is no significant deviation of postoperative achieved values of FEV1 from predicted ones obtained by both methods, and there is no significant differences between predicted values (ppoFEV1) obtained by spirometry and perfusion scintigraphy. Conclusion: It is necessary to asses the postoperative pulmonary function before lung resection to avoid postoperative respiratory failure and other cardiopulmonary complications. It is absolutely necessary for pneumonectomy, i.e.. maximal pulmonary resection. It can be done with great possibility using spirometry or perfusion lung scintigraphy. PMID:23378687

  7. Tiny Device Mimics Human Lung Function

    ScienceCinema

    McDonald, Rebecca; Harris, Jennifer; Nath, Pulak

    2016-07-12

    Scientists at Los Alamos National Laboratory are developing a miniature, tissue-engineered artificial lung that mimics the response of the human lung to drugs, toxins and other agents. “We breathe in and out thousands of times every day. And while we have control over what we eat or drink, we don’t always have control over what we breathe in,” said Jennifer Harris of Biosecurity and Public Health at Los Alamos, "and so we’re making this miniature lung to be able to test on actual human cells whether something in the environment, or a drug, is toxic or harmful to us." Nicknamed “PuLMo” for Pulmonary Lung Model (Pulmo is also the Latin word for "lung")the device consists of two major parts, the bronchiolar unit and the alveolar unit—just like the human lung. The units are primarily made from various polymers and are connected by a microfluidic “circuit board” that manages fluid and air flow. “When we build our lung, we not only take into account the aspects of different cell types, the tissues that are involved, we also take into account that a lung is supposed to breathe, so PuLMo actually breathes,” said Pulak Nath of Applied Modern Physics, who leads engineering efforts for the project. The most exciting application of PuLMo is a potentially revolutionary improvement in the reliability of drug-toxicity assessments and the prediction of new pharmaceutical success in humans, according to Harris. The PuLMo may also be designed to mimic lung disease conditions, such as Chronic Obstructive Pulmonary Disease (COPD) and asthma, and may be used to study lung air-flow dynamics to better understand the mechanisms of toxins and drug delivery and the effects of smoking, particularly the less-understood effects of e-cigarettes.

  8. Hyperpolarized Xenon-129 Magnetic Resonance Imaging of Functional Lung Microstructure

    NASA Astrophysics Data System (ADS)

    Dregely, Isabel

    Hyperpolarized 129Xe (HXe) is a non-invasive contrast agent for lung magnetic resonance imaging (MRI), which upon inhalation follows the functional pathway of oxygen in the lung by dissolving into lung tissue structures and entering the blood stream. HXe MRI therefore provides unique opportunities for functional lung imaging of gas exchange which occurs from alveolar air spaces across the air-blood boundary into parenchymal tissue. However challenges in acquisition speed and signal-to-noise ratio have limited the development of a HXe imaging biomarker to diagnose lung disease. This thesis addresses these challenges by introducing parallel imaging to HXe MRI. Parallel imaging requires dedicated hardware. This work describes design, implementation, and characterization of a 32-channel phased-array chest receive coil with an integrated asymmetric birdcage transmit coil tuned to the HXe resonance on a 3 Tesla MRI system. Using the newly developed human chest coil, a functional HXe imaging method, multiple exchange time xenon magnetization transfer contrast (MXTC) is implemented. MXTC dynamically encodes HXe gas exchange into the image contrast. This permits two parameters to be derived regionally which are related to gas-exchange functionality by characterizing tissue-to-alveolar-volume ratio and alveolar wall thickness in the lung parenchyma. Initial results in healthy subjects demonstrate the sensitivity of MXTC by quantifying the subtle changes in lung microstructure in response to orientation and lung inflation. Our results in subjects with lung disease show that the MXTC-derived functional tissue density parameter exhibits excellent agreement with established imaging techniques. The newly developed dynamic parameter, which characterizes the alveolar wall, was elevated in subjects with lung disease, most likely indicating parenchymal inflammation. In light of these observations we believe that MXTC has potential as a biomarker for the regional quantification of 1

  9. Regional lung function and mechanics using image registration

    NASA Astrophysics Data System (ADS)

    Ding, Kai

    The main function of the respiratory system is gas exchange. Since many disease or injury conditions can cause biomechanical or material property changes that can alter lung function, there is a great interest in measuring regional lung function and mechanics. In this thesis, we present a technique that uses multiple respiratory-gated CT images of the lung acquired at different levels of inflation with both breath-hold static scans and retrospectively reconstructed 4D dynamic scans, along with non-rigid 3D image registration, to make local estimates of lung tissue function and mechanics. We validate our technique using anatomical landmarks and functional Xe-CT estimated specific ventilation. The major contributions of this thesis include: (1) developing the registration derived regional expansion estimation approach in breath-hold static scans and dynamic 4DCT scans, (2) developing a method to quantify lobar sliding from image registration derived displacement field, (3) developing a method for measurement of radiation-induced pulmonary function change following a course of radiation therapy, (4) developing and validating different ventilation measures in 4DCT. The ability of our technique to estimate regional lung mechanics and function as a surrogate of the Xe-CT ventilation imaging for the entire lung from quickly and easily obtained respiratory-gated images, is a significant contribution to functional lung imaging because of the potential increase in resolution, and large reductions in imaging time, radiation, and contrast agent exposure. Our technique may be useful to detect and follow the progression of lung disease such as COPD, may be useful as a planning tool during RT planning, may be useful for tracking the progression of toxicity to nearby normal tissue during RT, and can be used to evaluate the effectiveness of a treatment post-therapy.

  10. Early airway infection, inflammation, and lung function in cystic fibrosis

    PubMed Central

    Nixon, G; Armstrong, D; Carzino, R; Carlin, J; Olinsky, A; Robertson, C; Grimwood, K

    2002-01-01

    Aims: To determine the relation between lower airway infection and inflammation, respiratory symptoms, and lung function in infants and young children with cystic fibrosis (CF). Methods: A prospective study of children with CF aged younger than 3 years, diagnosed by a newborn screening programme. All were clinically stable and had testing as outpatients. Subjects underwent bronchial lavage (BL) and lung function testing by the raised volume rapid thoracoabdominal compression technique under general anaesthesia. BL fluid was cultured and analysed for neutrophil count, interleukin 8, and neutrophil elastase. Lung function was assessed by forced expiratory volume in 0.5, 0.75, and 1 second. Results: Thirty six children with CF were tested on 54 occasions. Lower airway infection shown by BL was associated with a 10% reduction in FEV0.5 compared with subjects without infection. No relation was identified between airway inflammation and lung function. Daily moist cough within the week before testing was reported on 20/54 occasions, but in only seven (35%) was infection detected. Independent of either infection status or airway inflammation, those with daily cough had lower lung function than those without respiratory symptoms at the time of BL (mean adjusted FEV0.5 195 ml and 236 ml respectively). Conclusions: In young children with CF, both respiratory symptoms and airway infection have independent, additive effects on lung function, unrelated to airway inflammation. Further studies are needed to understand the mechanisms of airway obstruction in these young patients. PMID:12244003

  11. Systematic review of pleural plaques and lung function

    PubMed Central

    Kerper, Laura E.; Lynch, Heather N.; Zu, Ke; Tao, Ge; Utell, Mark J.

    2015-01-01

    Abstract Context US EPA proposed a Reference Concentration for Libby amphibole asbestos based on the premise that pleural plaques are adverse and cause lung function deficits. Objective We conducted a systematic review to evaluate whether there is an association between pleural plaques and lung function and ascertain whether results were dependent on the method used to identify plaques. Methods Using the PubMed database, we identified studies that evaluated pleural plaques and lung function. We assessed each study for quality, then integrated evidence and assessed associations based on the Bradford Hill guidelines. We also compared the results of HRCT studies to those of X-ray studies. Results We identified 16 HRCT and 36 X-ray studies. We rated six HRCT and 16 X-ray studies as higher quality based on a risk-of-bias analysis. Half of the higher quality studies reported small but statistically significant mean lung function decrements associated with plaques. None of the differences were clinically significant. Many studies had limitations, such as inappropriate controls and/or insufficient adjustment for confounders. There was little consistency in the direction of effect for the most commonly reported measurements. X-ray results were more variable than HRCT results. Pleural plaques were not associated with changes in lung function over time in longitudinal studies. Conclusion The weight of evidence indicates that pleural plaques do not impact lung function. Observed associations are most likely due to unidentified abnormalities or other factors. PMID:25518994

  12. Aspergillus fumigatus colonization in cystic fibrosis: implications for lung function?

    PubMed

    de Vrankrijker, A M M; van der Ent, C K; van Berkhout, F T; Stellato, R K; Willems, R J L; Bonten, M J M; Wolfs, T F W

    2011-09-01

    Aspergillus fumigatus is commonly found in the respiratory secretions of patients with cystic fibrosis (CF). Although allergic bronchopulmonary aspergillosis (ABPA) is associated with deterioration of lung function, the effects of A. fumigatus colonization on lung function in the absence of ABPA are not clear. This study was performed in 259 adults and children with CF, without ABPA. A. fumigatus colonization was defined as positivity of >50% of respiratory cultures in a given year. A cross-sectional analysis was performed to study clinical characteristics associated with A. fumigatus colonization. A retrospective cohort analysis was performed to study the effect of A. fumigatus colonization on lung function observed between 2002 and 2007. Longitudinal data were analysed with a linear mixed model. Sixty-one of 259 patients were at least intermittently colonized with A. fumigatus. An association was found between A. fumigatus colonization and increased age and use of inhaled antibiotics. In the longitudinal analysis, 163 patients were grouped according to duration of colonization. After adjustment for confounders, there was no significant difference in lung function between patients colonized for 0 or 1 year and patients with 2-3 or more than 3 years of colonization (p 0.40 and p 0.64) throughout the study. There was no significant difference in lung function decline between groups. Although colonization with A. fumigatus is more commonly found in patients with more severe lung disease and increased treatment burden, it is not independently associated with lower lung function or more severe lung function decline over a 5-year period.

  13. Impaired lymphatic function accelerates cancer growth

    PubMed Central

    Steinskog, Eli Sihn Samdal; Sagstad, Solfrid Johanne; Wagner, Marek; Karlsen, Tine Veronica; Yang, Ning; Markhus, Carl Erik; Yndestad, Synnøve; Wiig, Helge; Eikesdal, Hans Petter

    2016-01-01

    Increased lymphangiogenesis is a common feature of cancer development and progression, yet the influence of impaired lymphangiogenesis on tumor growth is elusive. C3HBA breast cancer and KHT-1 sarcoma cell lines were implanted orthotopically in Chy mice, harboring a heterozygous inactivating mutation of vascular endothelial growth factor receptor-3, resulting in impaired dermal lymphangiogenesis. Accelerated tumor growth was observed in both cancer models in Chy mice, coinciding with reduced peritumoral lymphangiogenesis. An impaired lymphatic washout was observed from the peritumoral area in Chy mice with C3HBA tumors, and the number of macrophages was significantly reduced. While fewer macrophages were detected, the fraction of CD163+ M2 macrophages remained constant, causing a shift towards a higher M2/M1 ratio in Chy mice. No difference in adaptive immune cells was observed between wt and Chy mice. Interestingly, levels of pro- and anti-inflammatory macrophage-associated cytokines were reduced in C3HBA tumors, pointing to an impaired innate immune response. However, IL-6 was profoundly elevated in the C3HBA tumor interstitial fluid, and treatment with the anti-IL-6 receptor antibody tocilizumab inhibited breast cancer growth. Collectively, our data indicate that impaired lymphangiogenesis weakens anti-tumor immunity and favors tumor growth at an early stage of cancer development. PMID:27329584

  14. Activation of p21(CIP1/WAF1) in mammary epithelium accelerates mammary tumorigenesis and promotes lung metastasis.

    PubMed

    Cheng, Xiaoyun; Xia, Weiya; Yang, Jer-Yen; Hsu, Jennifer L; Chou, Chao-Kai; Sun, Hui-Lung; Wyszomierski, Shannon L; Mills, Gordon B; Muller, William J; Yu, Dihua; Hung, Mien-Chie

    2010-12-03

    While p21 is well known to inhibit cyclin-CDK activity in the nucleus and it has also been demonstrated to have oncogenic properties in different types of human cancers. In vitro studies showed that the oncogenic function of p21is closely related to its cytoplasmic localization. However, it is unclear whether cytoplasmic p21 contributes to tumorigenesis in vivo. To address this question, we generated transgenic mice expressing the Akt-phosphorylated form of p21 (p21T145D) in the mammary epithelium. The results showed that Akt-activated p21 was expressed in the cytoplasm of mammary epithelium. Overexpression of Akt-activated p21 accelerated tumor onset and promoted lung metastasis in MMTV/neu mice, providing evidence that p21, especially cytoplasmic phosphorylated p21, has an oncogenic role in promoting mammary tumorigenesis and metastasis.

  15. Dispatching function calls across accelerator devices

    DOEpatents

    Jacob, Arpith C.; Sallenave, Olivier H.

    2017-01-10

    In one embodiment, a computer-implemented method for dispatching a function call includes receiving, at a supervisor processing element (PE) and from an origin PE, an identifier of a target device, a stack frame of the origin PE, and an address of a function called from the origin PE. The supervisor PE allocates a target PE of the target device. The supervisor PE copies the stack frame of the origin PE to a new stack frame on a call stack of the target PE. The supervisor PE instructs the target PE to execute the function. The supervisor PE receives a notification that execution of the function is complete. The supervisor PE copies the stack frame of the target PE to the stack frame of the origin PE. The supervisor PE releases the target PE of the target device. The supervisor PE instructs the origin PE to resume execution of the program.

  16. Dispatching function calls across accelerator devices

    DOEpatents

    Jacob, Arpith C.; Sallenave, Olivier H.

    2017-01-17

    In one embodiment, a computer-implemented method for dispatching a function call includes receiving, at a supervisor processing element (PE) and from an origin PE, an identifier of a target device, a stack frame of the origin PE, and an address of a function called from the origin PE. The supervisor PE allocates a target PE of the target device. The supervisor PE copies the stack frame of the origin PE to a new stack frame on a call stack of the target PE. The supervisor PE instructs the target PE to execute the function. The supervisor PE receives a notification that execution of the function is complete. The supervisor PE copies the stack frame of the target PE to the stack frame of the origin PE. The supervisor PE releases the target PE of the target device. The supervisor PE instructs the origin PE to resume execution of the program.

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

    PubMed

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

    2015-02-01

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

  18. Lung morphometry: the link between structure and function.

    PubMed

    Weibel, Ewald R

    2017-03-01

    The study of the structural basis of gas exchange function in the lung depends on the availability of quantitative information that concerns the structures establishing contact between the air in the alveoli and the blood in the alveolar capillaries, which can be entered into physiological equations for predicting oxygen uptake. This information is provided by morphometric studies involving stereological methods and allows estimates of the pulmonary diffusing capacity of the human lung that agree, in experimental studies, with the maximal oxygen consumption. The basis for this "machine lung" structure lies in the complex design of the cells building an extensive air-blood barrier with minimal cell mass.

  19. Adenosine promotes vascular barrier function in hyperoxic lung injury

    PubMed Central

    Davies, Jonathan; Karmouty‐Quintana, Harry; Le, Thuy T.; Chen, Ning‐Yuan; Weng, Tingting; Luo, Fayong; Molina, Jose; Moorthy, Bhagavatula; Blackburn, Michael R.

    2014-01-01

    Abstract Hyperoxic lung injury is characterized by cellular damage from high oxygen concentrations that lead to an inflammatory response in the lung with cellular infiltration and pulmonary edema. Adenosine is a signaling molecule that is generated extracellularly by CD73 in response to injury. Extracellular adenosine signals through cell surface receptors and has been found to be elevated and plays a protective role in acute injury situations. In particular, ADORA2B activation is protective in acute lung injury. However, little is known about the role of adenosine signaling in hyperoxic lung injury. We hypothesized that hyperoxia‐induced lung injury leads to CD73‐mediated increases in extracellular adenosine, which is protective through ADORA2B signaling pathways. To test this hypothesis, we exposed C57BL6, CD73−/−, and Adora2B−/− mice to 95% oxygen or room air and examined markers of pulmonary inflammation, edema, and monitored lung histology. Hyperoxic exposure caused pulmonary inflammation and edema in association with elevations in lung adenosine levels. Loss of CD73‐mediated extracellular adenosine production exacerbated pulmonary edema without affecting inflammatory cell counts. Furthermore, loss of the ADORA2B had similar results with worsening of pulmonary edema following hyperoxia exposure without affecting inflammatory cell infiltration. This loss of barrier function correlated with a decrease in occludin in pulmonary vasculature in CD73−/− and Adora2B−/− mice following hyperoxia exposure. These results demonstrate that exposure to a hyperoxic environment causes lung injury associated with an increase in adenosine concentration, and elevated adenosine levels protect vascular barrier function in hyperoxic lung injury through the ADORA2B‐dependent regulation of occludin. PMID:25263205

  20. Lung physiology during ECS resuscitation of DCD donors followed by in situ assessment of lung function.

    PubMed

    Reoma, Junewai L; Rojas, Alvaro; Krause, Eric M; Obeid, Nabeel R; Lafayette, Nathan G; Pohlmann, Joshua R; Padiyar, Niru P; Punch, Jeffery D; Cook, Keith E; Bartlett, Robert H

    2009-01-01

    Extracorporeal cardiopulmonary support (ECS) of donors after cardiac death (DCD) has been shown to improve abdominal organs for transplantation. This study assesses whether pulmonary congestion occurs during ECS with the heart arrested and describes an in vivo method to assess if lungs are suitable for transplantation from DCD donors after ECS resuscitation. Cardiac arrest was induced in 30 kg pigs, followed by 10 min of warm ischemia. Cannulae were placed into the right atrium (RA) and iliac artery, and veno-arterial ECS was initiated for 90 min with lungs inflated, group 1 (n = 5) or deflated, group 2 (n = 3). Left atrial pressures were measured as a marker for pulmonary congestion. After 90 min of ECS, lung function was evaluated. Cannulae were placed into the pulmonary artery (PA) and left ventricle (LV). A second pump was included, and ECS was converted to a bi-ventricular (bi-VAD) system. The RVAD drained from the RA and pumped into the PA, and the LVAD drained the LV and pumped into the iliac. This brought the lungs back into circulation for a 1-hr assessment period. The oxygenator was turned off, and ventilation was restarted. Flows, blood gases, PA and left atrial pressures, and compliance were recorded. In both the groups, LA pressure was <15 mm Hg during ECS. During the lung assessment period, PA flows were 1.4-2.2 L/min. PO2 was >300 mm Hg, with normal PCO2. Extracorporeal cardiopulmonary support resuscitation of DCD donors is feasible and allows for assessment of function before procurement. Extracorporeal cardiopulmonary support does not cause pulmonary congestion, and the lungs retain adequate function for transplantation. Compliance correlated with lung function.

  1. Hyperpolarized helium-3 mouse lung MRI: Studies of lung structure and function

    NASA Astrophysics Data System (ADS)

    Dugas, Joseph Paul

    Hyperpolarized 3He magnetic resonance imaging (MRI) of human and animal lungs has displayed promising and useful applications to studies of lung structure and function in both healthy and diseased lungs. Hyperpolarized 3He MRI allows the visualization of gas in the gas-exchange spaces of the lungs (as opposed to tissue) and has proven especially effective in studying diseases that are characterized by ventilation defects, such as emphysema. In particular, in-vivo measurements of the 3He apparent diffusion coefficient (ADC) can quantify lung structure by measuring its restrictive effects on the motion of 3He spins. This allows for detection and longitudinal tracking of changes in micro-architecture that result from disease destruction of alveolar walls. Due, in part, to the difficulties inherent in administering and imaging hyperpolarized 3He within the small (0.5 cc volume) mouse lung, applications of hyperpolarized 3He MRI techniques to laboratory mice are scarce. We have been able to implement and improve the techniques of hyperpolarized 3He mouse lung MRI and subsequently apply them to studies of several mouse models of disease, including elastase-induced emphysema, smoking-induced emphysema, and lung cancer. Here we detail the design, development, and implementation of a versatile, electronically-controlled, small animal ventilator that is capable of delivering tiny volumes of hyperpolarized 3He, mixed with oxygen, to the mouse and is also compatible with both the easily depolarized 3He gas and the highly magnetic environment within and around an imaging magnet. Also described are NM techniques developed to improve the signal-to-noise ratio of our images and effectively utilize the gas hyperpolarization. Applications of these technologies and techniques to small animal models of disease are presented wherein we have measured up to a 35% increase in 3He ADC in mice with elastase-induced emphysema as compared to healthy mice. We also demonstrate the potential

  2. Functions and mechanisms of long noncoding RNAs in lung cancer

    PubMed Central

    Peng, Zhenzi; Zhang, Chunfang; Duan, Chaojun

    2016-01-01

    Lung cancer is a heterogeneous disease, and there is a lack of adequate biomarkers for diagnosis. Long noncoding RNAs (lncRNAs) are emerging as an important set of molecules because of their roles in various key pathophysiological pathways, including cell growth, apoptosis, and metastasis. We review the current knowledge of the lncRNAs in lung cancer. In-depth analyses of lncRNAs in lung cancer have increased the number of potential effective biomarkers, thus providing options to increase the therapeutic benefit. In this review, we summarize the functions, mechanisms, and regulatory networks of lncRNAs in lung cancer, providing a basis for further research in this field. PMID:27499635

  3. Comparative study of lung functions in swimmers and runners.

    PubMed

    Sable, Meenakshi; Vaidya, S M; Sable, S S

    2012-01-01

    In the present study pulmonary function tests of two different groups of athletes, swimmers and runners were studied and compared. Thirty swimmers who used to swim a distance of two to three kilometers per day regularly were compared with age, sex, height, and weight matched thirty middle distance runners. Runners and swimmers selected for this study were undergoing training since last three years. Tidal Volume (TV), forced Vital Capacity (FVC). Forced expiratory volume in one second (FEV1) and maximum voluntary ventilation (MVV) were higher in swimmers than runners. Swimming exercise affects lung volume measurements as respiratory muscles including diaphragm of swimmers are required to develop greater pressure as a consequence of immersion in water during respiratory cycle, thus may lead to functional improvement in these muscles and also alterations in elasticity of lung and chest wall or of ventilatory muscles, leading to an improvement in forced vital capacity and other lung functions of swimmers than runners.

  4. [Pediatric lung resection. A case series and evaluation of postoperative lung function].

    PubMed

    Caussade, S; Zúñiga, S; García, C; González, S; Campos, E; Soto, G; Zúñiga, F; Sánchez, I

    2001-12-01

    The most common causes of pulmonary lobectomy in children are congenital lung malformations (CLM) and bronchiectasias. Our aim was to present the causes and clinical course and lung function of lobectomized patients. Between 1990 and July 1999 27 lobectomies were performed on patients whose ages ranged from newborn to 14 years. Lobectomies were performed to correct CLM in 124 cases and for acquired pulmonary disease (APD) in 13. Among CLM cases, half (n = 7) had cystic adenomatoid malformation. Among the APD patients, 10 had bronchiectasias, with etiological confirmation in 6 cases (3 secondary to serious adenovirus infection). Mean hospital stay was 4.6 days among those who experienced no postoperative complications. Symptoms resolved after surgery for most symptomatic patients. Lung function tests could be carried out with 8 patients over 6 years old whose operations had taken place 7 to 78 months earlier (x = 35 months) and whose age at the time of surgery was a mean 7 years 6 months (range 60 to 144 months). Spirometry showed normal forced vital capacity for 7 of 8 patients (87 to 143% of theoretical value). Arterial oxygen saturation measured during and after a 6-minute walking test was normal for 7 of 8 patients. Chest films showed reduced lung volume on the affected side in 5 of 8 patients. In summary, lobectomy is a procedure with few complications. It requires a short hospital stay and has good postoperative prognosis. Function and x-ray studies show adequate lung growth and development, with normal lung function in those who could be so examined because they were old enough to cooperate.

  5. Integrative pathway genomics of lung function and airflow obstruction.

    PubMed

    Gharib, Sina A; Loth, Daan W; Soler Artigas, María; Birkland, Timothy P; Wilk, Jemma B; Wain, Louise V; Brody, Jennifer A; Obeidat, Ma'en; Hancock, Dana B; Tang, Wenbo; Rawal, Rajesh; Boezen, H Marike; Imboden, Medea; Huffman, Jennifer E; Lahousse, Lies; Alves, Alexessander C; Manichaikul, Ani; Hui, Jennie; Morrison, Alanna C; Ramasamy, Adaikalavan; Smith, Albert Vernon; Gudnason, Vilmundur; Surakka, Ida; Vitart, Veronique; Evans, David M; Strachan, David P; Deary, Ian J; Hofman, Albert; Gläser, Sven; Wilson, James F; North, Kari E; Zhao, Jing Hua; Heckbert, Susan R; Jarvis, Deborah L; Probst-Hensch, Nicole; Schulz, Holger; Barr, R Graham; Jarvelin, Marjo-Riitta; O'Connor, George T; Kähönen, Mika; Cassano, Patricia A; Hysi, Pirro G; Dupuis, Josée; Hayward, Caroline; Psaty, Bruce M; Hall, Ian P; Parks, William C; Tobin, Martin D; London, Stephanie J

    2015-12-01

    Chronic respiratory disorders are important contributors to the global burden of disease. Genome-wide association studies (GWASs) of lung function measures have identified several trait-associated loci, but explain only a modest portion of the phenotypic variability. We postulated that integrating pathway-based methods with GWASs of pulmonary function and airflow obstruction would identify a broader repertoire of genes and processes influencing these traits. We performed two independent GWASs of lung function and applied gene set enrichment analysis to one of the studies and validated the results using the second GWAS. We identified 131 significantly enriched gene sets associated with lung function and clustered them into larger biological modules involved in diverse processes including development, immunity, cell signaling, proliferation and arachidonic acid. We found that enrichment of gene sets was not driven by GWAS-significant variants or loci, but instead by those with less stringent association P-values. Next, we applied pathway enrichment analysis to a meta-analyzed GWAS of airflow obstruction. We identified several biologic modules that functionally overlapped with those associated with pulmonary function. However, differences were also noted, including enrichment of extracellular matrix (ECM) processes specifically in the airflow obstruction study. Network analysis of the ECM module implicated a candidate gene, matrix metalloproteinase 10 (MMP10), as a putative disease target. We used a knockout mouse model to functionally validate MMP10's role in influencing lung's susceptibility to cigarette smoke-induced emphysema. By integrating pathway analysis with population-based genomics, we unraveled biologic processes underlying pulmonary function traits and identified a candidate gene for obstructive lung disease.

  6. Integrative pathway genomics of lung function and airflow obstruction

    PubMed Central

    Gharib, Sina A.; Loth, Daan W.; Soler Artigas, María; Birkland, Timothy P.; Wilk, Jemma B.; Wain, Louise V.; Brody, Jennifer A.; Obeidat, Ma'en; Hancock, Dana B.; Tang, Wenbo; Rawal, Rajesh; Boezen, H. Marike; Imboden, Medea; Huffman, Jennifer E.; Lahousse, Lies; Alves, Alexessander C.; Manichaikul, Ani; Hui, Jennie; Morrison, Alanna C.; Ramasamy, Adaikalavan; Smith, Albert Vernon; Gudnason, Vilmundur; Surakka, Ida; Vitart, Veronique; Evans, David M.; Strachan, David P.; Deary, Ian J.; Hofman, Albert; Gläser, Sven; Wilson, James F.; North, Kari E.; Zhao, Jing Hua; Heckbert, Susan R.; Jarvis, Deborah L.; Probst-Hensch, Nicole; Schulz, Holger; Barr, R. Graham; Jarvelin, Marjo-Riitta; O'Connor, George T.; Kähönen, Mika; Cassano, Patricia A.; Hysi, Pirro G.; Dupuis, Josée; Hayward, Caroline; Psaty, Bruce M.; Hall, Ian P.; Parks, William C.; Tobin, Martin D.; London, Stephanie J.

    2015-01-01

    Chronic respiratory disorders are important contributors to the global burden of disease. Genome-wide association studies (GWASs) of lung function measures have identified several trait-associated loci, but explain only a modest portion of the phenotypic variability. We postulated that integrating pathway-based methods with GWASs of pulmonary function and airflow obstruction would identify a broader repertoire of genes and processes influencing these traits. We performed two independent GWASs of lung function and applied gene set enrichment analysis to one of the studies and validated the results using the second GWAS. We identified 131 significantly enriched gene sets associated with lung function and clustered them into larger biological modules involved in diverse processes including development, immunity, cell signaling, proliferation and arachidonic acid. We found that enrichment of gene sets was not driven by GWAS-significant variants or loci, but instead by those with less stringent association P-values. Next, we applied pathway enrichment analysis to a meta-analyzed GWAS of airflow obstruction. We identified several biologic modules that functionally overlapped with those associated with pulmonary function. However, differences were also noted, including enrichment of extracellular matrix (ECM) processes specifically in the airflow obstruction study. Network analysis of the ECM module implicated a candidate gene, matrix metalloproteinase 10 (MMP10), as a putative disease target. We used a knockout mouse model to functionally validate MMP10's role in influencing lung's susceptibility to cigarette smoke-induced emphysema. By integrating pathway analysis with population-based genomics, we unraveled biologic processes underlying pulmonary function traits and identified a candidate gene for obstructive lung disease. PMID:26395457

  7. Leg joint function during walking acceleration and deceleration.

    PubMed

    Qiao, Mu; Jindrich, Devin L

    2016-01-04

    Although constant-average-velocity walking has been extensively studied, less is known about walking maneuvers that change speed. We investigated the function of individual leg joints when humans walked at a constant speed, accelerated or decelerated. We hypothesized that leg joints make different functional contributions to maneuvers. Specifically, we hypothesized that the hip generates positive mechanical work (acting like a "motor"), the knee generates little mechanical work (acting like a "strut"), and the ankle absorbs energy during the first half of stance and generates energy during the second half (consistent with "spring"-like function). We recorded full body kinematics and kinetics, used inverse dynamics to estimate net joint moments, and decomposed joint function into strut-, motor-, damper-, and spring-like components using indices based on net joint work. Although overall leg mechanics were primarily strut-like, individual joints did not act as struts during stance. The hip functioned as a power generating "motor," and ankle function was consistent with spring-like behavior. Even though net knee work was small, the knee did not behave solely as a strut but also showed motor-, and damper-like function. Acceleration involved increased motor-like function of the hip and ankle. Deceleration involved decreased hip motor-like function and ankle spring-like function and increased damping at the knee and ankle. Changes to joint mechanical work were primarily due to changes in joint angular displacements and not net moments. Overall, joints maintain different functional roles during unsteady locomotion.

  8. Lung function in infants and young children with chronic lung disease of infancy: the next steps?

    PubMed

    Stocks, Janet; Coates, Allan; Bush, Andrew

    2007-01-01

    Over the past year, a series of papers have reviewed the literature concerning assessment and interpretation of lung function in infants and young children with chronic lung disease of infancy. This manuscript, which represents the final paper in that series, summarizes the findings to date and highlights key areas for future research. Despite the huge literature in this field, interpretation of results and their use in guiding clinical management are still limited by difficulties in 'normalizing data' according to body size and maturation and selection of appropriate control groups. Furthermore, sensitive tests that more closely reflect the underlying pathophysiology of 'new' bronchopulmonary dysplasia, together with simple and reliable methods of assessing lung maturity at birth and true oxygen requirements at specified time points are urgently required. Research in this field is also challenged by the need to separate the independent effects of genetic predisposition, gene-environment interactions, preterm delivery, neonatal respiratory disorders and various treatment strategies on the growing lung. The extent to which disruption of lung growth following premature exposure to the extra-uterine environment leads to an earlier or more aggravated decline in respiratory function in later adult life remains to be elucidated. Whatever its origin, given the increasing survival of smaller and more immature infants, the long term sequelae of neonatal lung disease, are likely to continue to change, requiring ongoing, carefully designed longitudinal studies. Future research strategies need to encompass a multicenter, multi-disciplinary, collaborative approach with closer links between clinicians and basic scientists, to ensure that the most relevant research questions are addressed using appropriate methodology and that findings are implemented into clinical practice in a more timely fashion.

  9. Socioeconomic Status and Longitudinal Lung Function of Healthy Mexican Children

    PubMed Central

    Martínez-Briseño, David; Fernández-Plata, Rosario; Gochicoa-Rangel, Laura; Torre-Bouscoulet, Luis; Rojas-Martínez, Rosalba; Mendoza-Alvarado, Laura; García-Sancho, Cecilia; Pérez-Padilla, Rogelio

    2015-01-01

    Introduction Our aim was to estimate the longitudinal effect of Socioeconomic status (SES) on lung function growth of Mexican children and adolescents. Materials and Methods A cohort of Mexican children in third grade of primary school was followed with spirometry twice a year for 6 years through secondary school. Multilevel mixed-effects lineal models were fitted for the spirometric variables of 2,641 respiratory-healthy Mexican children. Monthly family income (in 2002 U.S. dollars [USD]) and parents’ years completed at school were used as proxies of SES. Results Individuals with higher SES tended to have greater height for age, and smaller sitting height/standing height and crude lung function. For each 1-year increase of parents’ schooling, Forced expiratory volume in 1 sec (FEV1) and Forced vital capacity (FVC) increased 8.5 (0.4%) and 10.6 mL (0.4%), respectively (p <0.05) when models were adjusted for gender. Impact of education on lung function was reduced drastically or abolished on adjusting by anthropometric variables and ozone. Conclusions Higher parental schooling and higher monthly family income were associated with higher lung function in healthy Mexican children, with the majority of the effect likely due to the increase in height-for-age. PMID:26379144

  10. Feasibility of measuring lung function in preschool children

    PubMed Central

    Nystad, W; Samuelsen, S; Nafstad, P; Edvardsen, E; Stensrud, T; Jaakkola, J

    2002-01-01

    Background: There have been difficulties in applying spirometric tests to children of preschool age. Methods: The feasibility of measuring lung function was examined in 652 children aged 3–6 years using dynamic spirometry with an animation programme and the guidelines approved by the European Respiratory Society. Results: Data from 603 (92%) children with at least two acceptable forced expiratory manoeuvres were analysed; 408 (68%) achieved at least three acceptable manoeuvres. Children with only two acceptable manoeuvres were younger, shorter, and weighed less (p<0.001). The lower levels of lung function in this group were partly explained by body size. 63% of those with three acceptable manoeuvres had a difference of ≤5% between the highest and second highest forced expiratory volume in 1 second (FEV1); when a difference of ≤10% was applied, 91% of the children were included. A similar trend was seen for forced vital capacity (FVC). The acceptability and reproducibility increased with increasing age, and levels of lung function increased linearly with age. The linear regression model showed that standing height was a satisfactory predictor of lung function; the explained fraction of variance (R2) was 59% for FEV1. Most FVC manoeuvres in children older than 3 years were acceptable and reproducible. Conclusions: Spirometric testing is feasible in preschool children and may be useful for both clinical practice and research. This study may fill the deficiency in reference values for European preschool children. PMID:12454295

  11. Gas cooking and reduced lung function in school children

    NASA Astrophysics Data System (ADS)

    Moshammer, Hanns; Hutter, Hans-Peter; Neuberger, Manfred

    RationaleOutdoor nitrogen dioxide (NO 2) is associated with reduced respiratory health. This could be due to a unique biological effect of this gaseous pollutant or because it serves as a surrogate of fine particles from incineration sources. Cooking with gas in small kitchens produces high concentrations of gaseous irritants (mainly nitrogen dioxide), but not fine particles. ObjectivesTo study the relative impact of cooking with gas on lung function parameters in a cross sectional study of school children. MethodsNearly all elementary school children (2898 children aged 6-10 years) living in the city of Linz (capital of Upper Austria) underwent lung function testing. In a questionnaire administered simultaneously to their parents, information on household conditions including cooking and tobacco smoke exposure was collected. Impact of cooking with gas on lung function controlling for various confounders was analyzed using loglinear multiple regression. ResultsGas cooking reduced lung function parameters ranging from 1.1% (not significant) for MEF 25 up to 3.4% ( p=0.01) for peak expiratory flow (PEF). ConclusionsGas stoves can have an adverse impact on children's respiratory health. Parents and caretakers should be advised to insure good ventilation while and after cooking, especially in small and poorly ventilated rooms. This study adds to the growing evidence that gaseous pollutants from incineration sources affect respiratory health directly.

  12. Can Particulate Pollution Affect Lung Function in Healthy Adults?

    EPA Science Inventory

    Accompanying editorial to paper from Harvard by Rice et al. entitled "Long-Term Exposure to Traffic Emissions and Fine Particulate Matter and Lung Function Decline in the Framingham Heart StudyBy almost any measure the Clean Air Act and its amendments has to be considered as one...

  13. Effects of nanoparticles on the mechanical functioning of the lung.

    PubMed

    Arick, Davis Q; Choi, Yun Hwa; Kim, Hyun Chang; Won, You-Yeon

    2015-11-01

    Nanotechnology is a rapidly expanding field that has very promising applications that will improve industry, medicine, and consumer products. However, despite the growing widespread use of engineered nanoparticles in these areas, very little has been done to assess the potential health risks they may pose to high-risk areas of the body, particularly the lungs. In this review we first briefly discuss the structure of the lungs and establish that the pulmonary surfactant (PS), given its vulnerability and huge contribution to healthy lung function, is a mechanism of great concern when evaluating potential nanoparticle interactions within the lung. To warrant that these interactions can occur, studies on the transport of nanoaerols are reviewed to highlight that a plethora of factors contribute to a nanoparticle's ability to travel to the deep regions of the lung where PS resides. The focus of this review is to determine the extent that physicochemical characteristics of nanoparticles such as size, hydrophobicity, and surface charge effect PS function. Numerous nanoparticle types are taken into consideration in order to effectively evaluate observed consistencies across numerous nanoparticle types and develop general trends that exist among the physicochemical characteristics of interest. Biological responses from other mechanisms/components of the lung are briefly discussed to provide further insights on how the toxicology of different nanoparticles is determined. We conclude by discussing general trends that summarize consistencies observed among the studies in regard to physicochemical properties and their effects on monolayer function, addressing current gaps in our understanding, and discussing the future outlook of this field of research.

  14. Lung function, breathing pattern, and gas exchange in interstitial lung disease.

    PubMed Central

    Javaheri, S; Sicilian, L

    1992-01-01

    BACKGROUND: The aim of this study was to determine the relation between the severity of abnormalities in ventilatory function tests and tidal breathing pattern and gas exchange indices in interstitial lung disease. METHODS: Pulmonary function, ventilation, carbon dioxide production, oxygen consumption, arterial blood gas tensions, and pH were measured during resting steady state conditions in 60 patients with proved interstitial lung disease. Patients were categorised by forced vital capacity (FVC) (percentage of predicted values) as having a mild, moderate, or severe restrictive defect with means (SD) of 71% (4%), 57% (4%), and 41% (7%) of predicted values, respectively. RESULTS: FVC varied from 29% to 79% of predicted values and from 0.99 l to 4.32 l. The two measurements of FVC correlated strongly with most static lung volumes and with transfer factor for carbon monoxide. Mean respiratory rates (per minute) and tidal volumes (ml) were 17 (4) and 484 (131), 20 (4) and 460 (139), and 23 (5) and 377 (109) in mild, moderate, and severe restrictive defects, respectively. FVC correlated negatively with respiratory rate and positively with tidal volume. Arterial carbon dioxide tension ranged from 30 to 49 mm Hg; only two patients were hypercapnic. Mean arterial oxygen tensions were not significantly different among the three groups, and there were no significant correlations between forced expiratory volume in one second or FVC and arterial carbon dioxide tension or carbon dioxide production. CONCLUSION: Low values of FVC were associated with increased respiratory rate and decreased tidal volume; this pattern of breathing mimics external elastic loading, suggesting that mechanoreceptors may contribute to the rapid and shallow pattern of breathing in interstitial lung disease. Hypercapnia seems to be rare in interstitial lung disease even when functional impairment is severe and tidal volume is small. The increased respiratory rate is important in maintaining adequate

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

    SciTech Connect

    Maasilta, P. )

    1991-03-01

    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.

  16. Shifting sources of functional limitation following extensive (70%) lung resection.

    PubMed

    Hsia, Connie C W; Dane, D Merrill; Estrera, Aaron S; Wagner, Harrieth E; Wagner, Peter D; Johnson, Robert L

    2008-04-01

    We previously found that, following surgical resection of approximately 58% of lung units by right pneumonectomy (PNX) in adult canines, oxygen-diffusing capacity (Dl(O(2))) fell sufficiently to become a major factor limiting exercise capacity, although the decline was mitigated by recruitment, remodeling, and growth of the remaining lung units. To determine whether an upper limit of compensation is reached following the loss of even more lung units, we measured pulmonary gas exchange, hemodynamics, and ventilatory power requirements in adult canines during treadmill exercise following two-stage resection of approximately 70% of lung units in the presence or absence of mediastinal distortion. Results were compared with that in control animals following right PNX or thoracotomy without resection (Sham). Following 70% lung resection, peak O(2) uptake was 45% below normal. Ventilation-perfusion mismatch developed, and pulmonary arterial pressure and ventilatory power requirements became markedly elevated. In contrast, the relationship of Dl(O(2)) to cardiac output remained normal, indicating preservation of Dl(O(2))-to-cardiac output ratio and alveolar-capillary recruitment up to peak exercise. The impairment in airway and vascular function exceeded the impairment in gas exchange and imposed the major limitation to exercise following 70% resection. Mediastinal distortion further reduced air and blood flow conductance, resulting in CO(2) retention. Results suggest that adaptation of extra-acinar airways and blood vessels lagged behind that of acinar tissue. As more lung units were lost, functional compensation became limited by the disproportionately reduced convective conductance rather than by alveolar diffusion disequilibrium.

  17. Combined administration of oseltamivir and hochu-ekki-to (TJ-41) dramatically decreases the viral load in lungs of senescence-accelerated mice during influenza virus infection.

    PubMed

    Ohgitani, Eriko; Kita, Masakazu; Mazda, Osam; Imanishi, Jiro

    2014-02-01

    To enhance the effect of anti-influenza-virus agent treatment, the effect of combined administration of oseltamivir phosphate and hochu-ekki-to (Japanese traditional herbal medicine, HET) on early viral clearance was examined. Senescence-accelerated mice were given HET in drinking water for 2 weeks, followed by intranasal infection with influenza A virus strain PR8. After 4 hours of infection, oseltamivir was administered orally for 5 days. The viral loads in the lungs of the group receiving combined treatment were dramatically lower when compared with the viral loads in the lungs of the group receiving oseltamivir alone. HET significantly increased the induction of IL-1β and TNF-α in the lungs of PR8-infected mice and stimulated alveolar macrophage phagocytosis. From these results, we conclude that these functions may be responsible the increased effect on viral load reduction. Here, we show that the combined administration of oseltamivir and HET is very useful for influenza treatment in senescence-accelerated mice.

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

    SciTech Connect

    Olivas-Calderón, Edgar; Recio-Vega, Rogelio; Gandolfi, A. Jay; Lantz, R. Clark; González-Cortes, Tania; Gonzalez-De Alba, Cesar; Froines, John R.; Espinosa-Fematt, Jorge A.

    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

  19. SU-E-T-436: Accelerated Gated IMRT: A Feasibility Study for Lung Cancer Patients

    SciTech Connect

    Gilles, M; Boussion, N; Visvikis, D; Fayad, H; Pradier, O

    2014-06-01

    Purpose: To evaluate the feasibility of delivering a gated Intensity Modulated Radiotherapy (IMRT) treatment using multiple respiratory phases in order to account for all anatomic changes during free breathing and accelerate the gated treatment without increasing the dose per fraction. Methods: For 7 patients with lung cancer, IMRT treatment plans were generated on a full inspiration (FI) Computed Tomography (CT) and a Mid Intensity Position (MIP) CT. Moreover, in order to achieve an accelerated gated IMRT, multiple respiratory phase plans were calculated: 2-phase plans including the FI and the full expiration phases, and 3-phase plans by adding the mid-inspiration phase. In order to assess the tolerance limits, plans' doses were registered and summed to the FI-based plan. Mean dose received by Organs at Risk (OARs) and target volumes were used to compare obtained plans. Results: The mean dose differences between the FI plans and the multi-phase plans never exceeded 0.4 Gy (Fig. 1). Concerning the clinical target volume these differences were even smaller: less than 0.1 Gy for both the 2-phase and 3-phase plans. Regarding the MIP treatment plan, higher doses in different healthy structures were observed, with a relative mean increase of 0.4 to 1.5 Gy. Finally, compared to the prescribed dose, the FI as well as the multi-phase plans were associated with a mean difference of 0.4 Gy, whereas in the case of MIP a higher mean difference of 0.6 Gy was observed. Conclusion: The doses obtained while planning a multi-phase gated IMRT treatment were within the tolerance limits. Compared to MIP, a better healthy tissue sparing was observed in the case of treatment planning based on one or multiple phases. Future work will consist in testing the multi-phase treatment delivery while accounting for the multileaf collimator speed constraints.

  20. Abnormalities of lung function in hay fever.

    PubMed Central

    Morgan, E J; Hall, D R

    1976-01-01

    Twenty subjects with symptoms of hay fever were studied to see whether abnormalities could be detected in the function of small airways. The investigations included dynamic compliance at varying respiratory frequencies, closing capacity, residual volume, transfer factor, and maximal expiratory flow-volume curves. The tests were repeated in the winter when symptoms had resolved. Frequency dependence of compliance was found in eight subjects with symptoms (40%), closing capacities being abnormal in only two instances. Conventional pulmonary function tests, including expiratory flow rates at mid vital capacity, were within the predicted range of all subjects. When tests were repeated in the winter, frequency dependence of compliance was no longer present in subjects whose symptoms had resolved. The study suggests that reversible small airway abnormalities are present in a significant proportion of subjects with symptoms of hay fever and that such abnormalities are best detected by the measurement of dynamic compliance at varying respiratory frequencies. PMID:769243

  1. Decreased proteasomal function accelerates cigarette smoke-induced pulmonary emphysema in mice.

    PubMed

    Yamada, Yosuke; Tomaru, Utano; Ishizu, Akihiro; Ito, Tomoki; Kiuchi, Takayuki; Ono, Ayako; Miyajima, Syota; Nagai, Katsura; Higashi, Tsunehito; Matsuno, Yoshihiro; Dosaka-Akita, Hirotoshi; Nishimura, Masaharu; Miwa, Soichi; Kasahara, Masanori

    2015-06-01

    Chronic obstructive pulmonary disease (COPD) is a disease common in elderly people, characterized by progressive destruction of lung parenchyma and chronic inflammation of the airways. The pathogenesis of COPD remains unclear, but recent studies suggest that oxidative stress-induced apoptosis in alveolar cells contributes to emphysematous lung destruction. The proteasome is a multicatalytic enzyme complex that plays a critical role in proteostasis by rapidly destroying misfolded and modified proteins generated by oxidative and other stresses. Proteasome activity decreases with aging in many organs including lungs, and an age-related decline in proteasomal function has been implicated in various age-related pathologies. However, the role of the proteasome system in the pathogenesis of COPD has not been investigated. Recently, we have established a transgenic (Tg) mouse model with decreased proteasomal chymotrypsin-like activity, showing age-related phenotypes. Using this model, we demonstrate here that decreased proteasomal function accelerates cigarette smoke (CS)-induced pulmonary emphysema. CS-exposed Tg mice showed remarkable airspace enlargement and increased foci of inflammation compared with wild-type controls. Importantly, apoptotic cells were found in the alveolar walls of the affected lungs. Impaired proteasomal activity also enhanced apoptosis in cigarette smoke extract (CSE)-exposed fibroblastic cells derived from mice and humans in vitro. Notably, aggresome formation and prominent nuclear translocation of apoptosis-inducing factor were observed in CSE-exposed fibroblastic cells isolated from Tg mice. Collective evidence suggests that CS exposure and impaired proteasomal activity coordinately enhance apoptotic cell death in the alveolar walls that may be involved in the development and progression of emphysema in susceptible individuals such as the elderly.

  2. Air pollution and fuel vapour induced changes in lung functions: are fuel handlers safe?

    PubMed

    Chawla, Anuj; Lavania, A K

    2008-01-01

    Automobile exhaust derived air pollutants have become a major health hazard. Coupled with the inhalation of fuel vapour, as occurs in petrol station workers, this may lead to significant impairment of lung function. Spirometric lung functions were studied in 58 petrol station workers to examine this possibility. The forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), forced expiratory flow 25%-75% (FEF25-75) and peak expiratory flow (PEF) were recorded and analysed separately for smokers and non-smokers. The workers were divided into 5 groups for analysis of data based on the number of years of work in the petrol pumps. Outdoor air analysis was also carried out. The FVC, FEV1 and PEF declined significantly with increasing years of work in petrol stations in both smokers and non-smokers. Smoking as an independent variable was found to affect the FEV1 significantly but not FVC or PEF. The FEF25-75 was found to be the most affected spirometric value with a significant reduction with increasing years of work. Smoking as such did not affect it. Oxides of nitrogen (NOx), suspended particulate matter (SPM) and particulate matter less than 10 microns (PM10) in outdoor air were higher than the national ambient air quality standards. Exposure to automobile exhaust and fuel vapour impairs lung function in a time-dependent manner. Cigarette smoking appears to accelerate the decline.

  3. Measurement of acceleration: a new method of monitoring neuromuscular function.

    PubMed

    Viby-Mogensen, J; Jensen, E; Werner, M; Nielsen, H K

    1988-01-01

    A new method for monitoring neuromuscular function based on measurement of acceleration is presented. The rationale behind the method is Newton's second law, stating that the acceleration is directly proportional to the force. For measurement of acceleration, a piezo-electric ceramic wafer was used. When this piezo electrode was fixed to the thumb, an electrical signal proportional to the acceleration was produced whenever the thumb moved in response to nerve stimulation. The electrical signal was registered and analysed in a Myograph 2000 neuromuscular transmission monitor. In 35 patients anaesthetized with halothane, train-of-four ratios measured with the accelerometer (ACT-TOF) were compared with simultaneous mechanical train-of-four ratios (FDT-TOF). Control ACT-TOF ratios were significantly higher than control FDT-TOF ratios: 116 +/- 12 and 98 +/- 4 (mean +/- s.d.), respectively. In five patients not given any relaxant during the anaesthetic procedure (20-60 min), both responses were remarkably constant. In 30 patients given vecuronium, a close linear relationship was found during recovery between ACT-TOF and FDT-TOF ratios. It is concluded that the method fulfils the basic requirements for a simple and reliable clinical monitoring tool.

  4. Factors affecting the development of lung function in Tunisian children.

    PubMed

    Trabelsi, Y; Pariès, J; Harrabi, I; Zbidi, A; Tabka, Z; Richalet, J P; Buvry, A

    2008-01-01

    We undertook to evaluate the impacts of morphology at birth, physical activity, anthropometric, socioeconomic and environmental factors on lung function in healthy Tunisian children. Pulmonary function parameters were measured with a Minato portable spirometer in a randomized population of 756 healthy children (388 males and 368 females) aged between 6 and 16. The morphology at birth, the gestational age, the physical activity, the socioeconomic status, the type of habitation, and the environmental factors were all assessed by a standard questionnaire. Using univariate analysis, we found that: (1) morphometric parameters (height, weight, maximal inspiratory, and expiratory perimeter), as well as sex were highly associated with pulmonary function parameters; (2) Height at birth showed strong significant relations with FVC, FEV(1), and FEV(1)/FVC; (3) lung function parameters were influenced by physical training of our children, socioeconomic status, indoor pollution, and passive smoking; and (4) we did not observe any association between the gestational age and the weight at their birth and lung function parameters. Using a general linear model analysis, morphometric parameters, age, sex, type of heating, and maximal inspiratory and expiratory perimeters had significant relation with respiratory parameters. In our population of healthy Tunisian children, the main predictive factors of the pulmonary development were the morphological factors such as height, weight, maximal inspiratory, and expiratory thoracic perimeter, sex and age, and the environmental conditions such as type of heating but not morphology at birth, physical activity, or socioeconomic status.

  5. Acceleration of lung metastasis by up-regulation of CD44 expression in osteosarcoma-derived cell transplanted mice.

    PubMed

    Shiratori, H; Koshino, T; Uesugi, M; Nitto, H; Saito, T

    2001-09-20

    The effect of CD44-phenotypic expression on metastasis to the lung was studied using a spontaneous murine osteosarcoma-derived cell line, POS-1, stimulated with lipopolysaccharide (LPS). POS-1 cells were inoculated into the hind paws of 20 C3H/HeJ mice and produced a visible mass in all mice in 5 weeks, and these transplanted tumors resulted in lung metastasis in all mice. The number of metastatic foci in the lungs was 12.0+/-2.1 (mean+/-SD) with LPS-stimulated cells, which was significantly higher than that of unstimulated cells (5.8+/-1.4; N=10 for each; P<0.05). Hyaluronate (HA), a ligand of CD44, inhibited a number of lung metastases in a dose-dependent manner (0.5% HA, 3.0+/-1.1; 0.005% HA, 5.1+/-1.5; without HA, 8.6+/-1.7; N=10 for each; P<0.05, each group with HA versus the group without HA). Adhesion assay by coculturing POS-1 cells and lung microvascular endothelial cells on culture plate showed that the adhesion was significantly lower in HA treated POS-1 than those without HA (1.18+/-0.12 and 2.74+/-0.17, respectively, P<0.05). These results suggest that lung metastasis was accelerated by up-regulation of CD44.

  6. Wnt/β-catenin signaling accelerates mouse lung tumorigenesis by imposing an embryonic distal progenitor phenotype on lung epithelium.

    PubMed

    Pacheco-Pinedo, Eugenia C; Durham, Amy C; Stewart, Kathleen M; Goss, Ashley M; Lu, Min Min; Demayo, Francesco J; Morrisey, Edward E

    2011-05-01

    Although mutations in Kras are present in 21% of lung tumors, there is a high level of heterogeneity in phenotype and outcome among patients with lung cancer bearing similar mutations, suggesting that other pathways are important. Wnt/β-catenin signaling is a known oncogenic pathway that plays a well-defined role in colon and skin cancer; however, its role in lung cancer is unclear. We have shown here that activation of Wnt/β-catenin in the bronchiolar epithelium of the adult mouse lung does not itself promote tumor development. However, concurrent activation of Wnt/β-catenin signaling and expression of a constitutively active Kras mutant (KrasG12D) led to a dramatic increase in both overall tumor number and size compared with KrasG12D alone. Activation of Wnt/β-catenin signaling altered the KrasG12D tumor phenotype, resulting in a phenotypic switch from bronchiolar epithelium to the highly proliferative distal progenitors found in the embryonic lung. This was associated with decreased E-cadherin expression at the cell surface, which may underlie the increased metastasis of tumors with active Wnt/β-catenin signaling. Together, these data suggest that activation of Wnt/β-catenin signaling can combine with other oncogenic pathways in lung epithelium to produce a more aggressive tumor phenotype by imposing an embryonic distal progenitor phenotype and by decreasing E-cadherin expression.

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

    PubMed Central

    Olivas-Calderón, Edgar; Recio-Vega, Rogelio; Gandolfi, A. Jay; Lantz, R. Clark; González-Cortes, Tania; Alba, Cesar Gonzalez-De; Froines, John R.; Espinosa-Fematt, Jorge A.

    2016-01-01

    Evidence suggests that exposure to arsenic in drinking water during early childhood or in utero is associated with an increase in respiratory symptoms and diseases in adulthood, however only a few studies have been carried out during those sensitive windows of exposure. Recently our group demonstrated that exposure to arsenic during early childhood or in utero was associated with impairment in the lung function in children and suggested that this adverse effect could be due to a chronic inflammatory response to the metalloid. Therefore, a cross-sectional study was designed 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 As 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 Endproducts (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), monomethylarsenic 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. PMID:26048584

  8. Changes in Functional Lung Regions During the Course of Radiation Therapy and Their Potential Impact on Lung Dosimetry for Non-Small Cell Lung Cancer

    SciTech Connect

    Meng, Xue; Frey, Kirk; Matuszak, Martha; Paul, Stanton; Ten Haken, Randall; Yu, Jinming; Kong, Feng-Ming

    2014-05-01

    Purpose: To study changes in functional activity on ventilation (V)/perfusion (Q) single-photon emission computed tomography (SPECT) during radiation therapy (RT) and explore the impact of such changes on lung dosimetry in patients with non-small cell lung cancer (NSCLC). Methods and Materials: Fifteen NSCLC patients with centrally located tumors were enrolled. All patients were treated with definitive RT dose of ≥60 Gy. V/Q SPECT-CT scans were performed prior to and after delivery of 45 Gy of fractionated RT. SPECT images were used to define temporarily dysfunctional regions of lung caused by tumor or other potentially reversible conditions as B3. The functional lung (FL) was defined on SPECT by 2 separate approaches: FL1, a threshold of 30% of the maximum uptake of the patient's lung; and FL2, FL1 plus B3 region. The impact of changes in FL between initiation of RT and delivery of 45 Gy on lung dosimetry were analyzed. Results: Fourteen patients (93%) had larger FL2 volumes than FL1 pre-RT (P<.001). Dysfunctional lung became functional in 11 patients (73%) on V SPECT and in 10 patients (67%) on Q SPECT. The dosimetric parameters generated from CT-based anatomical lung had significantly lower values in FL1 than FL2, with a median reduction in the volume of lung receiving a dose of at least 20 Gy (V{sub 20}) of 3%, 5.6%, and mean lung dose of 0.95 and 1.55 on V and Q SPECT respectively. Conclusions: Regional ventilation and perfusion function improve significantly during RT in centrally located NSCLC. Lung dosimetry values vary notably between different definitions of functional lung.

  9. A Function of Lung Surfactant Protein SP-B

    NASA Astrophysics Data System (ADS)

    Longo, M. L.; Bisagno, A. M.; Zasadzinski, J. A. N.; Bruni, R.; Waring, A. J.

    1993-07-01

    The primary function of lung surfactant is to form monolayers at the alveolar interface capable of lowering the normal surface tension to near zero. To accomplish this process, the surfactant must be capable of maintaining a coherent, tightly packed monolayer that avoids collapse during expiration. The positively charged amino-terminal peptide SP-B1-25 of lung surfactant-specific protein SP-B increases the collapse pressure of an important component of lung surfactant, palmitic acid (PA), to nearly 70 millinewtons per meter. This alteration of the PA isotherms removes the driving force for "squeeze-out" of the fatty acids from the primarily dipalmitoylphosphatidylcholine monolayers of lung surfactant. An uncharged mutant of SP-B1-25 induced little change in the isotherms, suggesting that a specific charge interaction between the cationic peptide and the anionic lipid is responsible for the stabilization. The effect of SP-B1-25 on fatty acid isotherms is remarkably similar to that of simple poly-cations, suggesting that such polymers might be useful as components of replacement surfactants for the treatment of respiratory distress syndrome.

  10. NK cell activating receptor ligand expression in lymphangioleiomyomatosis is associated with lung function decline

    PubMed Central

    Osterburg, Andrew R.; Nelson, Rebecca L.; Yaniv, Benyamin Z.; Foot, Rachel; Donica, Walter R.F.; Nashu, Madison A.; Liu, Huan; Wikenheiser-Brokamp, Kathryn A.; Moss, Joel; McCormack, Francis X.; Borchers, Michael T.

    2016-01-01

    Lymphangioleiomyomatosis (LAM) is a rare lung disease of women that leads to progressive cyst formation and accelerated loss of pulmonary function. Neoplastic smooth muscle cells from an unknown source metastasize to the lung and drive destructive remodeling. Given the role of NK cells in immune surveillance, we postulated that NK cell activating receptors and their cognate ligands are involved in LAM pathogenesis. We found that ligands for the NKG2D activating receptor UL-16 binding protein 2 (ULBP2) and ULBP3 are localized in cystic LAM lesions and pulmonary nodules. We found elevated soluble serum ULBP2 (mean = 575 pg/ml ± 142) in 50 of 100 subjects and ULBP3 in 30 of 100 (mean = 8,300 pg/ml ± 1,515) subjects. LAM patients had fewer circulating NKG2D+ NK cells and decreased NKG2D surface expression. Lung function decline was associated with soluble NKG2D ligand (sNKG2DL) detection. The greatest rate of decline forced expiratory volume in 1 second (FEV1, –124 ± 30 ml/year) in the 48 months after enrollment (NHLBI LAM Registry) occurred in patients expressing both ULBP2 and ULBP3, whereas patients with undetectable sNKG2DL levels had the lowest rate of FEV1 decline (–32.7 ± 10 ml/year). These data suggest a role for NK cells, sNKG2DL, and the innate immune system in LAM pathogenesis. PMID:27734028

  11. Association between lung function and airway wall density

    NASA Astrophysics Data System (ADS)

    Leader, J. Ken; Zheng, Bin; Fuhrman, Carl R.; Tedrow, John; Park, Sang C.; Tan, Jun; Pu, Jiantao; Drescher, John M.; Gur, David; Sciurba, Frank C.

    2009-02-01

    Computed tomography (CT) examination is often used to quantify the relation between lung function and airway remodeling in chronic obstructive pulmonary disease (COPD). In this preliminary study, we examined the association between lung function and airway wall computed attenuation ("density") in 200 COPD screening subjects. Percent predicted FVC (FVC%), percent predicted FEV1 (FEV1%), and the ratio of FEV1 to FVC as a percentage (FEV1/FVC%) were measured post-bronchodilator. The apical bronchus of the right upper lobe was manually selected from CT examinations for evaluation. Total airway area, lumen area, wall area, lumen perimeter and wall area as fraction of the total airway area were computed. Mean HU (meanHU) and maximum HU (maxHU) values were computed across pixels assigned membership in the wall and with a HU value greater than -550. The Pearson correlation coefficients (PCC) between FVC%, FEV1%, and FEV1/FVC% and meanHU were -0.221 (p = 0.002), -0.175 (p = 0.014), and -0.110 (p = 0.123), respectively. The PCCs for maxHU were only significant for FVC%. The correlations between lung function and the airway morphometry parameters were slightly stronger compared to airway wall density. MeanHU was significantly correlated with wall area (PCC = 0.720), airway area (0.498) and wall area percent (0.611). This preliminary work demonstrates that airway wall density is associated with lung function. Although the correlations in our study were weaker than a recent study, airway wall density initially appears to be an important parameter in quantitative CT analysis of COPD.

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

    PubMed Central

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

    2012-01-01

    Background 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. Methods Children (n=3273) aged 6–12 years were recruited from eight schools in four 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 three years (1993–1996). Dichotomous samplers placed in each schoolyard were used to measure PM2.5 and PM10 (PM with diameter ≤ 2.5 and ≤ 10, respectively). Multivariable generalized estimating equations were used to examine the association between the quarterly average PM levels and lung function growth over the period of follow-up. Results Annual average PM2.5 and PM10 levels in the four cities ranged from 57 to 158 μg/m3 and 95 to 268 μg/m3, respectively. In multivariable models, an increase of 10 μg/m3 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. Conclusions Exposure to ambient particulate matter was associated with decreased growth in lung function among Chinese children. PMID:22407138

  13. The relation of airway size to lung function

    NASA Astrophysics Data System (ADS)

    Leader, J. Ken; Zheng, Bin; Sciurba, Frank C.; Fuhrman, Carl R.; Bon, Jessica M.; Park, Sang C.; Pu, Jiantao; Gur, David

    2008-03-01

    Chronic obstructive pulmonary disease may cause airway remodeling, and small airways are the mostly likely site of associated airway flow obstruction. Detecting and quantifying airways depicted on a typical computed tomography (CT) images is limited by spatial resolution. In this study, we examined the association between lung function and airway size. CT examinations and spirometry measurement of forced expiratory volume in one second as a percent predicted (FEV I%) from 240 subjects were used in this study. Airway sections depicted in axial CT section were automatically detected and quantified. Pearson correlation coefficients (PCC) were computed to compare lung function across three size categories: (1) all detected airways, (2) the smallest 50% of detected airways, and (3) the largest 50% of detected airways using the CORANOVA test. The mean number of all airways detected per subject was 117.4 (+/- 40.1) with mean size ranging from 20.2 to 50.0 mm2. The correlation between lung function (i.e., FEV I) and airway morphometry associated with airway remodeling and airflow obstruction (i.e., lumen perimeter and wall area as a percent of total airway area) was significantly stronger for smaller compared to larger airways (p < 0.05). The PCCs between FEV I and all airways, the smallest 50%, and the largest 50% were 0.583, 0.617, 0.523, respectively, for lumen perimeter and -0.560, -0.584, and -0.514, respectively, for wall area percent. In conclusion, analyzing a set of smaller airways compared to larger airways may improve detection of an association between lung function and airway morphology change.

  14. Lung function and radiographic change in chrysotile workers in Swaziland.

    PubMed Central

    McDermott, M; Bevan, M M; Elmes, P C; Allardice, J T; Bradley, A C

    1982-01-01

    The effect on lung function and radiographic indices of exposure to chrysotile asbestos was investigated by cross-sectional studies in two groups of men at Havelock Mine, Swaziland. The first group consisted of 214 employees and ex-employees, mean age 52, who had been employed for at least 10 years, and whose dust exposure ranged from minimal for surface workers to very heavy for those in the grading and bagging sections of the mill. In this group 29% had category 1 or more simple pneumoconiosis and 4.5% category 2 or more. For surface and mine workers, the estimated annual deterioration in FEV1 and FVC and the increase in category of pneumoconiosis was similar to that due to age alone, while the heaviest exposure almost doubled the decline in lung function and trebled the rate of progression of pneumoconiosis. The second group consisted of 224 men, mean age 33, all currently working in the mill and having been employed there for at least a year. In this group 30% had category 1 or more simple pneumoconiosis, and 2.7% category 2. Exposure in the dustiest sections of the mill more than doubled the estimated annual decline in lung function and doubled the rate of progression of pneumoconiosis. PMID:6291579

  15. Rubberwood dust and lung function among Thai furniture factory workers.

    PubMed

    Thetkathuek, Anamai; Yingratanasuk, Tanongsak; Demers, Paul A; Thepaksorn, Phayong; Saowakhontha, Sastri; Keifer, Matthew C

    2010-01-01

    The objective of this study was to assess factors affecting lung function among 685 workers in the rubberwood (Hevea brasiliensis) furniture industry in the Chonburi and Rayung provinces of eastern Thailand. Study data were gathered using questionnaires, by sampling wood dust, and by spirometry. The mean wood dust exposure level in the factories was 4.08 mg/m3 (SD = 1.42, range: 1.15-11.17 mg/m3). The mean overall percent of predicted forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and FEV1/FVC values were 84 % (SD = 13.41), 86 % (SD = 14.40), and 99% (SD = 10.42), respectively. Significant negative correlations were found between mean dust exposure levels and FVC (p = 0.0008), and FEV1/FVC% (p < 0.001), but not FEV1 (p = 0.074). An association between decline in lung function and wood dust levels among wood workers suggests that rubberwood dust exposure negatively affects lung function.

  16. GPU-accelerated Block Matching Algorithm for Deformable Registration of Lung CT Images

    PubMed Central

    Li, Min; Xiang, Zhikang; Xiao, Liang; Castillo, Edward; Castillo, Richard; Guerrero, Thomas

    2016-01-01

    Deformable registration (DR) is a key technology in the medical field. However, many of the existing DR methods are time-consuming and the registration accuracy needs to be improved, which prevents their clinical applications. In this study, we propose a parallel block matching algorithm for lung CT image registration, in which the sum of squared difference metric is modified as the cost function and the moving least squares approach is used to generate the full displacement field. The algorithm is implemented on Graphic Processing Unit (GPU) with the Compute Unified Device Architecture (CUDA). Results show that the proposed parallel block matching method achieves a fast runtime while maintaining an average registration error (standard deviation) of 1.08 (0.69) mm. PMID:28042622

  17. GPU-accelerated Block Matching Algorithm for Deformable Registration of Lung CT Images.

    PubMed

    Li, Min; Xiang, Zhikang; Xiao, Liang; Castillo, Edward; Castillo, Richard; Guerrero, Thomas

    2015-12-01

    Deformable registration (DR) is a key technology in the medical field. However, many of the existing DR methods are time-consuming and the registration accuracy needs to be improved, which prevents their clinical applications. In this study, we propose a parallel block matching algorithm for lung CT image registration, in which the sum of squared difference metric is modified as the cost function and the moving least squares approach is used to generate the full displacement field. The algorithm is implemented on Graphic Processing Unit (GPU) with the Compute Unified Device Architecture (CUDA). Results show that the proposed parallel block matching method achieves a fast runtime while maintaining an average registration error (standard deviation) of 1.08 (0.69) mm.

  18. Engineering functionality gradients by dip coating process in acceleration mode.

    PubMed

    Faustini, Marco; Ceratti, Davide R; Louis, Benjamin; Boudot, Mickael; Albouy, Pierre-Antoine; Boissière, Cédric; Grosso, David

    2014-10-08

    In this work, unique functional devices exhibiting controlled gradients of properties are fabricated by dip-coating process in acceleration mode. Through this new approach, thin films with "on-demand" thickness graded profiles at the submillimeter scale are prepared in an easy and versatile way, compatible for large-scale production. The technique is adapted to several relevant materials, including sol-gel dense and mesoporous metal oxides, block copolymers, metal-organic framework colloids, and commercial photoresists. In the first part of the Article, an investigation on the effect of the dip coating speed variation on the thickness profiles is reported together with the critical roles played by the evaporation rate and by the viscosity on the fluid draining-induced film formation. In the second part, dip-coating in acceleration mode is used to induce controlled variation of functionalities by playing on structural, chemical, or dimensional variations in nano- and microsystems. In order to demonstrate the full potentiality and versatility of the technique, original graded functional devices are made including optical interferometry mirrors with bidirectional gradients, one-dimensional photonic crystals with a stop-band gradient, graded microfluidic channels, and wetting gradient to induce droplet motion.

  19. GENETIC ASSOCIATION BETWEEN HUMAN CHITINASES AND LUNG FUNCTION IN COPD

    PubMed Central

    Aminuddin, F.; Akhabir, L.; Stefanowicz, D.; Paré, P.D.; Connett, J.E.; Anthonisen, N.R.; Fahy, J.V.; Seibold, M.A.; Burchard, E.G.; Eng, C.; Gulsvik, A.; Bakke, P.; Cho, M. H.; Litonjua, A.; Lomas, D.A.; Anderson, W. H.; Beaty, T.H.; Crapo, J.D.; Silverman, E.K.; Sandford, A.J.

    2013-01-01

    Two primary chitinases have been identified in humans – acid mammalian chitinase (AMCase) and chitotriosidase (CHIT1). Mammalian chitinases have been observed to affect the host’s immune response. The aim of this study was to test for association between genetic variation in the chitinases and phenotypes related to Chronic Obstructive Pulmonary Disease (COPD). Polymorphisms in the chitinase genes were selected based on previous associations with respiratory diseases. Polymorphisms that were associated with lung function level or rate of decline in the Lung Health Study (LHS) cohort were analyzed for association with COPD affection status in four other COPD case-control populations. Chitinase activity and protein levels were also related to genotypes. In the Caucasian LHS population, the baseline forced expiratory volume in one second (FEV1) was significantly different between the AA and GG genotypic groups of the AMCase rs3818822 polymorphism. Subjects with the GG genotype had higher AMCase protein and chitinase activity compared with AA homozygotes. For CHIT1 rs2494303, a significant association was observed between rate of decline in FEV1 and the different genotypes. In the African American LHS population, CHIT1 rs2494303 and AMCase G339T genotypes were associated with rate of decline in FEV1. Although a significant effect of chitinase gene alleles was found on lung function level and decline in the LHS, we were unable to replicate the associations with COPD affection status in the other COPD study groups. PMID:22200767

  20. Accelerated radiotherapy and concurrent chemotherapy for patients with contralateral central or mediastinal lung cancer relapse after pneumonectomy

    PubMed Central

    Abu Jawad, Jehad; Gkika, Eleni; Freitag, Lutz; Lübcke, Wolfgang; Welter, Stefan; Gauler, Thomas; Schuler, Martin; Eberhardt, Wilfried Ernst Erich; Stamatis, Georgios; Stuschke, Martin

    2015-01-01

    Background Treatment options are very limited for patients with lung cancer who experience contralateral central or mediastinal relapse following pneumonectomy. We present results of an accelerated salvage chemoradiotherapy regimen. Methods Patients with localized contralateral central intrapulmonary or mediastinal relapse after pneumonectomy were offered combined chemoradiotherapy including concurrent weekly cisplatin (25 mg/m2) and accelerated radiotherapy [accelerated fractionated (AF), 60 Gy, 8×2 Gy per week] to reduce time for repopulation. Based on 4D-CT-planning, patients were irradiated using multifield intensity-modulated radiotherapy (IMRT) or helical tomotherapy. Results Between 10/2011 and 12/2012, seven patients were treated. Initial stages were IIB/IIIA/IIIB: 3/1/3; histopathological subtypes scc/adeno/large cell: 4/1/2. Tumour relapses were located in mediastinal nodal stations in five patients with endobronchial tumour in three patients. The remaining patients had contralateral central tumour relapses. All patients received 60 Gy (AF), six patients received concurrent chemotherapy. Median dose to the remaining contralateral lung, esophagus, and spinal cord was 6.8 (3.3-11.4), 8.0 (5.1-15.5), and 7.6 (2.8-31.2) Gy, respectively. With a median follow-up of 29 [17-32] months, no esophageal or pulmonary toxicity exceeding grade 2 [Common terminology criteria for adverse events (CTC-AE) v. 3] was observed. Median survival was 17.2 months, local in-field control at 12 months 80%. Only two local recurrences were observed, both in combination with out-field metastases. Conclusions This intensified accelerated chemoradiotherapy schedule was safely applicable and offers a curative chance in these pretreated frail lung cancer patients. PMID:25922702

  1. Genome-wide study identifies two loci associated with lung function decline in mild to moderate COPD

    PubMed Central

    Hansel, Nadia N; Ruczinski, Ingo; Rafaels, Nicholas; Sin, Don D; Daley, Denise; Malinina, Alla; Huang, Lili; Sandford, Andrew; Murray, Tanda; Kim, Yoonhee; Vergara, Candelaria; Heckbert, Susan R; Psaty, Bruce M; Li, Guo; Elliott, W. Mark; Aminuddin, Farzian; Dupuis, Josée; O’Connor, George; Doheny, Kimberly; Scott, Alan F; Boezen, H Marike; Postma, Dirkje S; Smolonska, Joanna; Zanen, Pieter; Mohamed Hoesein, Firdaus A; de Koning, Harry J; Crystal, Ron; Tanaka, Toshiko; Ferrucci, Luigi; Silverman, Edwin; Wan, Emily; Vestbo, Jorgen; Lomas, David A; Connett, John; Wise, Robert A; Neptune, Enid R; Mathias, Rasika A; Paré, Peter D; Beaty, Terri H; Barnes, Kathleen C

    2012-01-01

    Rationale Accelerated lung function decline is a key COPD phenotype; however its genetic control remains largely unknown. Methods We performed a genome-wide association study using the Illumina Human660W-Quad v.1_A BeadChip. Generalized estimation equations were used to assess genetic contributions to lung function decline over a 5-year period in 4,048 European-American Lung Health Study participants with largely mild COPD. Genotype imputation was performed using reference HapMap II data. To validate regions meeting genome-wide significance, replication of top SNPs was attempted in independent cohorts. Three genes (TMEM26, ANK3 and FOXA1) within the regions of interest were selected for tissue expression studies using immunohistochemistry. Measurements and Main Results Two intergenic SNPs (rs10761570, rs7911302) on chromosome 10 and one SNP on chromosome 14 (rs177852) met genome-wide significance after Bonferroni. Further support for the chromosome 10 region was obtained by imputation, the most significantly associated imputed SNPs (rs10761571, rs7896712) being flanked by observed markers rs10761570 and rs7911302. Results were not replicated in four general population cohorts or a smaller cohort of subjects with moderate to severe COPD; however, we show novel expression of genes near regions of significantly associated SNPS, including TMEM26 and FOXA1 in airway epithelium and lung parenchyma, and ANK3 in alveolar macrophages. Levels of expression were associated with lung function and COPD status. Conclusions We identified two novel regions associated with lung function decline in mild COPD. Genes within these regions were expressed in relevant lung cells and their expression related to airflow limitation suggesting they may represent novel candidate genes for COPD susceptibility. PMID:22986903

  2. Fibroblast Activation Protein (FAP) Accelerates Collagen Degradation and Clearance from Lungs in Mice.

    PubMed

    Fan, Ming-Hui; Zhu, Qiang; Li, Hui-Hua; Ra, Hyun-Jeong; Majumdar, Sonali; Gulick, Dexter L; Jerome, Jacob A; Madsen, Daniel H; Christofidou-Solomidou, Melpo; Speicher, David W; Bachovchin, William W; Feghali-Bostwick, Carol; Puré, Ellen

    2016-04-08

    Idiopathic pulmonary fibrosis is a disease characterized by progressive, unrelenting lung scarring, with death from respiratory failure within 2-4 years unless lung transplantation is performed. New effective therapies are clearly needed. Fibroblast activation protein (FAP) is a cell surface-associated serine protease up-regulated in the lungs of patients with idiopathic pulmonary fibrosis as well as in wound healing and cancer. We postulate that FAP is not only a marker of disease but influences the development of pulmonary fibrosis after lung injury. In two different models of pulmonary fibrosis, intratracheal bleomycin instillation and thoracic irradiation, we find increased mortality and increased lung fibrosis in FAP-deficient mice compared with wild-type mice. Lung extracellular matrix analysis reveals accumulation of intermediate-sized collagen fragments in FAP-deficient mouse lungs, consistent within vitrostudies showing that FAP mediates ordered proteolytic processing of matrix metalloproteinase (MMP)-derived collagen cleavage products. FAP-mediated collagen processing leads to increased collagen internalization without altering expression of the endocytic collagen receptor, Endo180. Pharmacologic FAP inhibition decreases collagen internalization as expected. Conversely, restoration of FAP expression in the lungs of FAP-deficient mice decreases lung hydroxyproline content after intratracheal bleomycin to levels comparable with that of wild-type controls. Our findings indicate that FAP participates directly, in concert with MMPs, in collagen catabolism and clearance and is an important factor in resolving scar after injury and restoring lung homeostasis. Our study identifies FAP as a novel endogenous regulator of fibrosis and is the first to show FAP's protective effects in the lung.

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

    SciTech Connect

    Bishawi, Muath; Kim, Bong; Moore, William H.; Bilfinger, Thomas V.

    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

  4. Loss of Mig6 accelerates initiation and progression of mutant epidermal growth factor receptor-driven lung adenocarcinoma

    PubMed Central

    Maity, Tapan K.; Venugopalan, Abhilash; Linnoila, Ilona; Cultraro, Constance M.; Giannakou, Andreas; Nemati, Roxanne; Zhang, Xu; Webster, Joshua D.; Ritt, Daniel; Ghosal, Sarani; Hoschuetzky, Heinz; Simpson, R. Mark; Biswas, Romi; Politi, Katerina; Morrison, Deborah K.; Varmus, Harold E.; Guha, Udayan

    2015-01-01

    Somatic mutations in the epidermal growth factor receptor (EGFR) kinase domain drive lung adenocarcinoma. We have previously identified MIG6, an inhibitor of ERBB signaling and a potential tumor suppressor, as a target for phosphorylation by mutant EGFRs. Here we demonstrate that Mig6 is a tumor suppressor for the initiation and progression of mutant EGFR-driven lung adenocarcinoma in mouse models. Mutant EGFR-induced lung tumor formation was accelerated in Mig6-deficient mice, even with Mig6 haploinsufficiency. We demonstrate that constitutive phosphorylation of MIG6 at Y394/395 in EGFR-mutant human lung adenocarcinoma cell lines is associated with an increased interaction of MIG6 with mutant EGFR, which may stabilize EGFR protein. MIG6 also fails to promote mutant EGFR degradation. We propose a model whereby increased tyrosine phosphorylation of MIG6 decreases its capacity to inhibit mutant EGFR. Nonetheless, the residual inhibition is sufficient for Mig6 to delay mutant EGFR-driven tumor initiation and progression in mouse models. PMID:25735773

  5. Paracrine Functions of Fibrocytes to Promote Lung Fibrosis

    PubMed Central

    Kleaveland, Kathryn R.; Moore, Bethany B.; Kim, Kevin K.

    2014-01-01

    Fibrocytes derive from the bone marrow and are found in the circulation. They can be recruited to sites of injury and contribute to repair/remodeling. In vitro evidence suggests that fibrocytes may differentiate into fibroblasts to promote lung fibrosis. However, in vivo evidence for this is sparse. This review summarizes recent literature which may suggest that fibrocytes function to promote fibrosis via paracrine actions. In this way, secretion of growth factors, proteases and matricellular proteins may strongly influence the actions of resident epithelial and mesenchymal cells to promote repair and resolution or to tip the scale towards pathologic remodeling. PMID:24451025

  6. Anti-Muscarinic Adjunct Therapy Accelerates Functional Human Oligodendrocyte Repair

    PubMed Central

    Abiraman, Kavitha; Pol, Suyog U.; O'Bara, Melanie A.; Chen, Guang-Di; Khaku, Zainab M.; Wang, Jing; Thorn, David; Vedia, Bansi H.; Ekwegbalu, Ezinne C.; Li, Jun-Xu; Salvi, Richard J.

    2015-01-01

    Therapeutic repair of myelin disorders may be limited by the relatively slow rate of human oligodendrocyte differentiation. To identify appropriate pharmacological targets with which to accelerate differentiation of human oligodendrocyte progenitors (hOPCs) directly, we used CD140a/O4-based FACS of human forebrain and microarray to hOPC-specific receptors. Among these, we identified CHRM3, a M3R muscarinic acetylcholine receptor, as being restricted to oligodendrocyte-biased CD140a+O4+ cells. Muscarinic agonist treatment of hOPCs resulted in a specific and dose-dependent blockade of oligodendrocyte commitment. Conversely, when hOPCs were cocultured with human neurons, M3R antagonist treatment stimulated oligodendrocytic differentiation. Systemic treatment with solifenacin, an FDA-approved muscarinic receptor antagonist, increased oligodendrocyte differentiation of transplanted hOPCs in hypomyelinated shiverer/rag2 brain. Importantly, solifenacin treatment of engrafted animals reduced auditory brainstem response interpeak latency, indicative of increased conduction velocity and thereby enhanced functional repair. Therefore, solifenacin and other selective muscarinic antagonists represent new adjunct approaches to accelerate repair by engrafted human progenitors. PMID:25716865

  7. Integrating functional genomics to accelerate mechanistic personalized medicine

    PubMed Central

    Tyner, Jeffrey W.

    2017-01-01

    The advent of deep sequencing technologies has resulted in the deciphering of tremendous amounts of genetic information. These data have led to major discoveries, and many anecdotes now exist of individual patients whose clinical outcomes have benefited from novel, genetically guided therapeutic strategies. However, the majority of genetic events in cancer are currently undrugged, leading to a biological gap between understanding of tumor genetic etiology and translation to improved clinical approaches. Functional screening has made tremendous strides in recent years with the development of new experimental approaches to studying ex vivo and in vivo drug sensitivity. Numerous discoveries and anecdotes also exist for translation of functional screening into novel clinical strategies; however, the current clinical application of functional screening remains largely confined to small clinical trials at specific academic centers. The intersection between genomic and functional approaches represents an ideal modality to accelerate our understanding of drug sensitivities as they relate to specific genetic events and further understand the full mechanisms underlying drug sensitivity patterns. PMID:28299357

  8. Integrating functional genomics to accelerate mechanistic personalized medicine.

    PubMed

    Tyner, Jeffrey W

    2017-03-01

    The advent of deep sequencing technologies has resulted in the deciphering of tremendous amounts of genetic information. These data have led to major discoveries, and many anecdotes now exist of individual patients whose clinical outcomes have benefited from novel, genetically guided therapeutic strategies. However, the majority of genetic events in cancer are currently undrugged, leading to a biological gap between understanding of tumor genetic etiology and translation to improved clinical approaches. Functional screening has made tremendous strides in recent years with the development of new experimental approaches to studying ex vivo and in vivo drug sensitivity. Numerous discoveries and anecdotes also exist for translation of functional screening into novel clinical strategies; however, the current clinical application of functional screening remains largely confined to small clinical trials at specific academic centers. The intersection between genomic and functional approaches represents an ideal modality to accelerate our understanding of drug sensitivities as they relate to specific genetic events and further understand the full mechanisms underlying drug sensitivity patterns.

  9. Lung function indices for predicting mortality in COPD

    PubMed Central

    Boutou, Afroditi K.; Shrikrishna, Dinesh; Tanner, Rebecca J.; Smith, Cayley; Kelly, Julia L.; Ward, Simon P.; Polkey, Michael I.; Hopkinson, Nicholas S.

    2013-01-01

    Chronic obstructive pulmonary disease (COPD) is characterised by high morbidity and mortality. It remains unknown which aspect of lung function carries the most prognostic information and if simple spirometry is sufficient. Survival was assessed in COPD outpatients whose data had been added prospectively to a clinical audit database from the point of first full lung function testing including spirometry, lung volumes, gas transfer and arterial blood gases. Variables univariately associated with survival were entered into a multivariate Cox proportional hazard model. 604 patients were included (mean±sd age 61.9±9.7 years; forced expiratory volume in 1 s 37±18.1% predicted; 62.9% males); 229 (37.9%) died during a median follow-up of 83 months. Median survival was 91.9 (95% CI 80.8–103) months with survival rates at 3 and 5 years 0.83 and 0.66, respectively. Carbon monoxide transfer factor % pred quartiles (best quartile (>51%): HR 0.33, 95% CI 0.172–0.639; and second quartile (51–37.3%): HR 0.52, 95% CI 0.322–0.825; versus lowest quartile (<27.9%)), age (HR 1.04, 95% CI 1.02–1.06) and arterial oxygen partial pressure (HR 0.85, 95% CI 0.77–0.94) were the only parameters independently associated with mortality. Measurement of gas transfer provides additional prognostic information compared to spirometry in patients under hospital follow-up and could be considered routinely. PMID:23349449

  10. Pulmonary physiology: future directions for lung function testing in COPD.

    PubMed

    Brusasco, Vito; Barisione, Giovanni; Crimi, Emanuele

    2015-02-01

    Chronic obstructive pulmonary disease (COPD) is a term that encompasses different pathological conditions having excessive airflow limitation in common. A wide body of knowledge has been accumulated over the last century explaining the mechanisms by which airway (chronic bronchitis) and parenchymal (emphysema) diseases lead to an indistinguishable spirometric abnormality. Although the definition of emphysema is anatomical, early studies showed that its presence can be inferred with good approximation from measurements of lung mechanics and gas exchange, in addition to simple spirometry. Studies using tests of ventilation distribution showed that abnormalities are present in smokers with normal spirometry, although these tests were not predictive of development of COPD. At the beginning of the third millennium, new documents and guidelines for diagnosis and treatment of COPD were developed, in which the functional diagnosis of COPD was restricted, for the sake of simplicity, to simple spirometry. In recent years, there has been a resurgence of interest in separating bronchitic from emphysematous phenotype of COPD. For this purpose, high-resolution computed tomography scanning has been added to diagnostic work-up. At the same time, methods for lung function testing have been refined and seem promising for detection of early small airways abnormalities. Among them are the forced oscillation technique and the nitrogen phase III slope analysis of the multiple-breath washout test, which may provide information on ventilation inhomogeneity. Moreover, the combined assessment of diffusing capacity for nitric oxide and carbon monoxide may be more sensitive than the latter alone for partitioning diffusive components at parenchymal level.

  11. Monitoring asthma in childhood: lung function, bronchial responsiveness and inflammation.

    PubMed

    Moeller, Alexander; Carlsen, Kai-Hakon; Sly, Peter D; Baraldi, Eugenio; Piacentini, Giorgio; Pavord, Ian; Lex, Christiane; Saglani, Sejal

    2015-06-01

    This review focuses on the methods available for measuring reversible airways obstruction, bronchial hyperresponsiveness (BHR) and inflammation as hallmarks of asthma, and their role in monitoring children with asthma. Persistent bronchial obstruction may occur in asymptomatic children and is considered a risk factor for severe asthma episodes and is associated with poor asthma outcome. Annual measurement of forced expiratory volume in 1 s using office based spirometry is considered useful. Other lung function measurements including the assessment of BHR may be reserved for children with possible exercise limitations, poor symptom perception and those not responding to their current treatment or with atypical asthma symptoms, and performed on a higher specialty level. To date, for most methods of measuring lung function there are no proper randomised controlled or large longitudinal studies available to establish their role in asthma management in children. Noninvasive biomarkers for monitoring inflammation in children are available, for example the measurement of exhaled nitric oxide fraction, and the assessment of induced sputum cytology or inflammatory mediators in the exhaled breath condensate. However, their role and usefulness in routine clinical practice to monitor and guide therapy remains unclear, and therefore, their use should be reserved for selected cases.

  12. Preoperative pulmonary rehabilitation for marginal-function lung cancer patients.

    PubMed

    Hashmi, Asra; Baciewicz, Frank A; Soubani, Ayman O; Gadgeel, Shirish M

    2017-01-01

    Background This study aimed to evaluate the impact of preoperative pulmonary rehabilitation in lung cancer patients undergoing pulmonary resection surgery with marginal lung function. Methods Short-term outcomes of 42 patients with forced expiratory volume in 1 s < 1.6 L who underwent lung resection between 01/2006 and 12/2010 were reviewed retrospectively. They were divided into group A (no preoperative pulmonary rehabilitation) and group B (receiving pulmonary rehabilitation). In group B, a second set of pulmonary function tests was obtained. Results There were no significant differences in terms of sex, age, race, pathologic stage, operative procedure, or smoking years. Mean forced expiratory volume in 1 s and diffusing capacity for carbon monoxide in group A was 1.40 ± 0.22 L and 10.28 ± 2.64 g∙dL(-1) vs. 1.39 ± 0.13 L and 10.75 ± 2.08 g∙dL(-1) in group B. Group B showed significant improvement in forced expiratory volume in 1 s from 1.39 ± 0.13 to 1.55 ± 0.06 L ( p = 0.02). Mean intensive care unit stay was 6 ± 5 days in group A vs. 9 ± 9 days in group B ( p = 0.22). Mean hospital stay was 10 ± 4 days in group A vs. 14 ± 9 days in group B ( p = 0.31). There was no significant difference in morbidity or mortality between groups. Conclusion Preoperative pulmonary rehabilitation can significantly improve forced expiratory volume in 1 s in some marginal patients undergoing lung cancer resection. However, it does not improve length of stay, morbidity, or mortality.

  13. SU-E-J-86: Lobar Lung Function Quantification by PET Galligas and CT Ventilation Imaging in Lung Cancer Patients

    SciTech Connect

    Eslick, E; Kipritidis, J; Keall, P; Bailey, D; Bailey, E

    2014-06-01

    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.

  14. Lung Function before and after a Large Chlorine Gas Release in Graniteville, South Carolina

    PubMed Central

    Karmaus, Wilfried J. J.; Mohr, Lawrence C.; Cai, Bo; Balte, Pallavi; Gibson, James J.; Ownby, Dennis; Lawson, Andrew B.; Vena, John E.; Svendsen, Erik R.

    2016-01-01

    Rationale: On January 6, 2005 a train derailment led to an estimated 54,915-kg release of chlorine at a local textile mill in Graniteville, South Carolina. Objectives: We used the employee health spirometry records of the textile to identify enduring effects of chlorine gas exposure resulting from the incident on the lung function of workers employed at the textile mill. Methods: Spirometry records from 1,807 mill workers (7,332 observations) were used from 4 years before and 18 months after the disaster. Longitudinal analysis using marginal regression models produced annual population mean estimates for FEV1, FVC, and FEV1/FVC ratio. Covariate adjustment was made for sex, age, smoking, height, season tested, technician, obesity, season × year interactions, and smoker × year interactions. The increased prevalence of mill workers having accelerated FEV1 decline was also evaluated after the chlorine spill. Measurements and Main Results: In the year of the accident, we observed a significant reduction in mean FEV1 (–4.2% predicted; P = 0.019) when compared with the year before the incident. In the second year, partial recovery in the mean FVC % predicted level was seen, but the cohort’s average FEV1/FVC ratio continued to decrease over time. Severe annual FEV1 decline was most prevalent in the year of the accident, and independent of mill worker smoking status. Conclusions: The Graniteville mill worker cohort revealed significant reductions in lung function immediately after the chlorine incident. Improvement was seen in the second year; but the proportion of mill workers experiencing accelerated FEV1 annual decline significantly increased in the 18 months after the chlorine incident. PMID:26695511

  15. Gravity effects on regional lung ventilation determined by functional EIT during parabolic flights.

    PubMed

    Frerichs, I; Dudykevych, T; Hinz, J; Bodenstein, M; Hahn, G; Hellige, G

    2001-07-01

    Gravity-dependent changes of regional lung function were studied during normogravity, hypergravity, and microgravity induced by parabolic flights. Seven healthy subjects were followed in the right lateral and supine postures during tidal breathing, forced vital capacity, and slow expiratory vital capacity maneuvers. Regional 1) lung ventilation, 2) lung volumes, and 3) lung emptying behavior were studied in a transverse thoracic plane by functional electrical impedance tomography (EIT). The results showed gravity-dependent changes of regional lung ventilation parameters. A significant effect of gravity on regional functional residual capacity with a rapid lung volume redistribution during the gravity transition phases was established. The most homogeneous functional residual capacity distribution was found at microgravity. During vital capacity and forced vital capacity in the right lateral posture, the decrease in lung volume on expiration was larger in the right lung region at all gravity phases. During tidal breathing, the differences in ventilation magnitudes between the right and left lung regions were not significant in either posture or gravity phase. A significant nonlinearity of lung emptying was determined at normogravity and hypergravity. The pattern of lung emptying was homogeneous during microgravity.

  16. Quantification of heterogeneity in lung disease with image-based pulmonary function testing

    PubMed Central

    Stahr, Charlene S.; Samarage, Chaminda R.; Donnelley, Martin; Farrow, Nigel; Morgan, Kaye S.; Zosky, Graeme; Boucher, Richard C.; Siu, Karen K. W.; Mall, Marcus A.; Parsons, David W.; Dubsky, Stephen; Fouras, Andreas

    2016-01-01

    Computed tomography (CT) and spirometry are the mainstays of clinical pulmonary assessment. Spirometry is effort dependent and only provides a single global measure that is insensitive for regional disease, and as such, poor for capturing the early onset of lung disease, especially patchy disease such as cystic fibrosis lung disease. CT sensitively measures change in structure associated with advanced lung disease. However, obstructions in the peripheral airways and early onset of lung stiffening are often difficult to detect. Furthermore, CT imaging poses a radiation risk, particularly for young children, and dose reduction tends to result in reduced resolution. Here, we apply a series of lung tissue motion analyses, to achieve regional pulmonary function assessment in β-ENaC-overexpressing mice, a well-established model of lung disease. The expiratory time constants of regional airflows in the segmented airway tree were quantified as a measure of regional lung function. Our results showed marked heterogeneous lung function in β-ENaC-Tg mice compared to wild-type littermate controls; identified locations of airway obstruction, and quantified regions of bimodal airway resistance demonstrating lung compensation. These results demonstrate the applicability of regional lung function derived from lung motion as an effective alternative respiratory diagnostic tool. PMID:27461961

  17. Lung function measurement with multiple-breath-helium washout system.

    PubMed

    Wang, J-Y; Suddards, M E; Mellor, C J; Owers-Bradley, J R

    2013-04-01

    Multiple-breath-washout (MBW) measurements are regarded as a sensitive technique which can reflect the ventilation inhomogeneity of respiratory airways. Typically nitrogen is used as the tracer gas and is washed out by pure oxygen in multiple-breath-nitrogen washout (MBNW) tests. In this study, instead of using nitrogen, (4)He is used as the tracer gas with smaller gas density which may be able to reach deeper into our lungs in a given time and the helium washout results may be more sensitive to the ventilation inhomogeneity in small airways. A multiple-breath-helium-washout (MBHW) system developed for the lung function study is also presented. Quartz tuning forks with a resonance frequency of 32,768Hz have been used for detecting the change of the respiratory gas density. The resonance frequency of the quartz tuning fork decreases linearly with increasing density of the surrounding gas. Knowing the CO2 concentration from the infrared carbon dioxide detector, the helium concentration can be determined. Results from 14 volunteers (3 mild asthmatics, 4 tobacco smokers, 1 with asthma history, 1 with COPD history, 5 normal) have shown that mild asthmatics have higher ventilation inhomogeneity in either conducting or acinar airways (or both). A feature has been found in washout curve of single breaths from 4 tobacco smokers with different length of smoking history which may indicate the early stage of respiratory ventilation inhomogeneity in acinar airways.

  18. Lung function in retired coke oven plant workers.

    PubMed Central

    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

  19. Changes in lung function during an extreme mountain ultramarathon.

    PubMed

    Vernillo, G; Rinaldo, N; Giorgi, A; Esposito, F; Trabucchi, P; Millet, G P; Schena, F

    2015-08-01

    This study aimed to assess the effects of an extreme mountain ultramarathon (MUM, 330 km, 24,000 D+) on lung function. Twenty-nine experienced male ultramarathon runners performed longitudinally [before (pre), during (mid), and immediately after (post) a MUM] a battery of pulmonary function tests. The tests included measurements of forced vital capacity, forced expiratory volume in 1 s, peak flow, inspiratory capacity, and maximum voluntary ventilation in 12 s (MVV12). A significant reduction in the running speed was observed (-43.0% between pre-mid and mid-post; P < 0.001). Expiratory function declined significantly at mid (P < 0.05) and at post (P < 0.05). A similar trend was observed for inspiratory function (P < 0.05). MVV12 declined at mid (P < 0.05) and further decreased at post (P < 0.05). Furthermore, there are significant negative correlations between performance time and MVV12 pre-race (R = -0.54, P = 0.02) as well as changes in MVV12 between pre- and post-race (R = -0.53, P = 0.009). It is concluded that during an extreme MUM, a continuous decline in pulmonary function was observed, likely attributable to the high levels of ventilation required during this MUM in a harsh mountainous environment.

  20. Melatonin decreases the expression of inflammation and apoptosis markers in the lung of a senescence-accelerated mice model.

    PubMed

    Puig, Ángela; Rancan, Lisa; Paredes, Sergio D; Carrasco, Adrián; Escames, Germaine; Vara, Elena; Tresguerres, Jesús A F

    2016-03-01

    Aging is associated with an increase in oxidative stress and inflammation. The aging lung is particularly affected since it is continuously exposed to environmental oxidants while antioxidant machinery weakens with age. Melatonin, a free radical scavenger, counteracts inflammation and apoptosis in healthy cells from several tissues. Its effects on the aging lung are, however, not yet fully understood. This study aimed to investigate the effect of chronic administration of melatonin on the expression of inflammation markers (TNF-α, IL-1β, NFκB2, HO-1) and apoptosis parameters (BAD, BAX, AIF) in the lung tissue of male senescence-accelerated prone mice (SAMP8). In addition, RNA oxidative damage, as the formation of 8-hydroxyguanosine (8-OHG), was also evaluated. Young and old animals, aged 2 and 10 months respectively, were divided into 4 groups: untreated young, untreated old, old mice treated with 1mg/kg/day melatonin, and old animals treated with 10mg/kg/day melatonin. Untreated young and old male senescence accelerated resistant mice (SAMR1) were used as controls. After 30 days of treatment, animals were sacrificed. Lungs were collected and immediately frozen in liquid nitrogen. mRNA and protein expressions were measured by RT-PCR and Western blotting, respectively. Levels of 8-OHG were quantified by ELISA. Mean values were analyzed using ANOVA. Old nontreated SAMP8 animals showed increased (p<0.05) mRNA and protein levels of TNF-α, IL-1β, NFκB2, and HO-1 compared to young mice and SAMR1 mice. Melatonin treatment with either dose reversed the aging-derived inflammation (p<0.05). BAD, BAX and AIF expressions also rose with aging, the effect being counteracted with melatonin (p<0.05). Aging also caused a significant elevation (p<0.05) in SAMP8 8-OHG values. This increase was not observed in animals treated with melatonin (p<0.05). In conclusion, melatonin treatment was able to modulate the inflammatory and apoptosis status of the aging lungs, exerting a

  1. Pilates Method for Lung Function and Functional Capacity in Obese Adults.

    PubMed

    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

  2. Effects of laparoscopic cholecystectomy on lung function: A systematic review

    PubMed Central

    Bablekos, George D; Michaelides, Stylianos A; Analitis, Antonis; Charalabopoulos, Konstantinos A

    2014-01-01

    AIM: To present and integrate findings of studies investigating the effects of laparoscopic cholecystectomy on various aspects of lung function. METHODS: We extensively reviewed literature of the past 24 years concerning the effects of laparoscopic cholecystectomy in comparison to the open procedure on many aspects of lung function including spirometric values, arterial blood gases, respiratory muscle performance and aspects of breathing control, by critically analyzing physiopathologic interpretations and clinically important conclusions. A total of thirty-four articles were used to extract information for the meta-analysis concerning the impact of the laparoscopic procedure on lung function and respiratory physiopathology. The quality of the literature reviewed was evaluated by the number of their citations and the total impact factor of the corresponding journals. A fixed and random effect meta-analysis was used to estimate the pooled standardized mean difference of studied parameters for laparoscopic (LC) and open (OC) procedures. A crude comparison of the two methods using all available information was performed testing the postoperative values expressed as percentages of the preoperative ones using the Mann-Whitney two-sample test. RESULTS: Most of the relevant studies have investigated and compared changes in spirometric parameters.The median percentage and interquartile range (IQR) of preoperative values in forced vital capacity (FVC), forced expiratory volume in 1 s and forced expiratory flow (FEF) at 25%-75% of FVC (FEF25%-75%) expressed as percentage of their preoperative values 24 h after LC and OC were respectively as follows: [77.6 (73.0, 80.0) L vs 55.4 (50.0, 64.0) L, P < 0.001; 76.0 (72.3, 81.0) L vs 52.5 (50.0, 56.7) L, P < 0.001; and 78.8 (68.8, 80.9) L/s vs 60.0 (36.1, 66.1) L/s, P = 0.005]. Concerning arterial blood gases, partial pressure of oxygen [PaO2 (kPa)] at 24 or 48 h after surgical treatment showed reductions that were significantly

  3. Respiratory symptoms and lung function among Danish woodworkers.

    PubMed

    Schlünssen, Vivi; Schaumburg, Inger; Taudorf, Ebbe; Mikkelsen, Anders B; Sigsgaard, Torben

    2002-01-01

    A cross-sectional study including 54 furniture factories and three control factories was conducted to survey lung function and prevalence of respiratory symptoms among woodworkers. Spirometry was performed on 2423 persons. Questionnaires regarding respiratory symptoms and wood dust exposure were completed by 2033 woodworkers and 474 controls. Personal passive dust measurements were performed on 1579 persons. The arithmetic mean +/- SD for equivalent inhalable dust was relatively low (1.19 +/- 0.86 mg/m3). Woodworkers had increased frequency of coughing with negative interaction between dust exposure and smoking. A dose-response relationship was seen between dust exposure and asthma symptoms, and a positive interaction for asthma was seen between female gender and dust exposure. Increased frequency of wheezing and a cross-shift decrease in forced expiratory volume in 1 second among workers using pinewood was seen. In conclusion, wood dust exposure might cause respiratory symptoms, despite a relatively low exposure level.

  4. Exploring Heart and Lung Function in Space: ARMS Experiments

    NASA Technical Reports Server (NTRS)

    Kuipers, Andre; Cork, Michael; LeGouic, Marine

    2002-01-01

    The Advanced Respiratory Monitoring System (ARMS) is a suite of monitoring instruments and supplies used to study the heart, lungs, and metabolism. Many experiments sponsored by the European Space Agency (ESA) will be conducted using ARMS during STS-107. The near-weightless environment of space causes the body to undergo many physiological adaptations, and the regulation of blood pressure is no exception. Astronauts also experience a decrease in blood volume as an adaptation to microgravity. Reduced blood volume may not provide enough blood pressure to the head during entry or landing. As a result, astronauts often experience light-headedness, and sometimes even fainting, when they stand shortly after returning to Earth. To help regulate blood pressure and heart rate, baroreceptors, sensors located in artery walls in the neck and near the heart, control blood pressure by sending information to the brain and ensuring blood flow to organs. These mechanisms work properly in Earth's gravity but must adapt in the microgravity environment of space. However, upon return to Earth during entry and landing, the cardiovascular system must readjust itself to gravity, which can cause fluctuation in the control of blood pressure and heart rate. Although the system recovers in hours or days, these occurrences are not easily predicted or understood - a puzzle investigators will study with the ARMS equipment. In space, researchers can focus on aspects of the cardiovascular system normally masked by gravity. The STS-107 experiments using ARMS will provide data on how the heart and lungs function in space, as well as how the nervous system controls them. Exercise will also be combined with breath holding and straining (the Valsalva maneuver) to test how heart rate and blood pressure react to different stresses. This understanding will improve astronauts' cardiopulmonary function after return to Earth, and may well help Earthbound patients who experience similar effects after long

  5. Proteasome function is not impaired in healthy aging of the lung.

    PubMed

    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.

  6. Phenotyping mouse pulmonary function in vivo with the lung diffusing capacity.

    PubMed

    Limjunyawong, Nathachit; Fallica, Jonathan; Ramakrishnan, Amritha; Datta, Kausik; Gabrielson, Matthew; Horton, Maureen; Mitzner, Wayne

    2015-01-06

    The mouse is now the primary animal used to model a variety of lung diseases. To study the mechanisms that underlie such pathologies, phenotypic methods are needed that can quantify the pathologic changes. Furthermore, to provide translational relevance to the mouse models, such measurements should be tests that can easily be done in both humans and mice. Unfortunately, in the present literature few phenotypic measurements of lung function have direct application to humans. One exception is the diffusing capacity for carbon monoxide, which is a measurement that is routinely done in humans. In the present report, we describe a means to quickly and simply measure this diffusing capacity in mice. The procedure involves brief lung inflation with tracer gases in an anesthetized mouse, followed by a 1 min gas analysis time. We have tested the ability of this method to detect several lung pathologies, including emphysema, fibrosis, acute lung injury, and influenza and fungal lung infections, as well as monitoring lung maturation in young pups. Results show significant decreases in all the lung pathologies, as well as an increase in the diffusing capacity with lung maturation. This measurement of lung diffusing capacity thus provides a pulmonary function test that has broad application with its ability to detect phenotypic structural changes with most of the existing pathologic lung models.

  7. Chronic effects of air pollution on lung function after lung transplantation in the Systems prediction of Chronic Lung Allograft Dysfunction (SysCLAD) study.

    PubMed

    Benmerad, Meriem; Slama, Rémy; Botturi, Karine; Claustre, Johanna; Roux, Antoine; Sage, Edouard; Reynaud-Gaubert, Martine; Gomez, Carine; Kessler, Romain; Brugière, Olivier; Mornex, Jean-François; Mussot, Sacha; Dahan, Marcel; Boussaud, Véronique; Danner-Boucher, Isabelle; Dromer, Claire; Knoop, Christiane; Auffray, Annick; Lepeule, Johanna; Malherbe, Laure; Meleux, Frederik; Nicod, Laurent; Magnan, Antoine; Pison, Christophe; Siroux, Valérie

    2017-01-01

    An irreversible loss in lung function limits the long-term success in lung transplantation. We evaluated the role of chronic exposure to ambient air pollution on lung function levels in lung transplant recipients (LTRs).The lung function of 520 LTRs from the Cohort in Lung Transplantation (COLT) study was measured every 6 months. The levels of air pollutants (nitrogen dioxide (NO2), particulate matter with an aerodynamic cut-off diameter of x µm (PMx) and ozone (O3)) at the patients' home address were averaged in the 12 months before each spirometry test. The effects of air pollutants on forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) in % predicted were estimated using mixed linear regressions. We assessed the effect modification of macrolide antibiotics in this relationship.Increased 12-month levels of pollutants were associated with lower levels of FVC % pred (-2.56%, 95% CI -3.86--1.25 for 5 µg·m(-3) of PM10; -0.75%, 95% CI -1.38--0.12 for 2 µg·m(-3) of PM2.5 and -2.58%, 95% CI -4.63--0.53 for 10 µg·m(-3) of NO2). In patients not taking macrolides, the deleterious association between PM and FVC tended to be stronger and PM10 was associated with lower FEV1Our study suggests a deleterious effect of chronic exposure to air pollutants on lung function levels in LTRs, which might be modified with macrolides.

  8. Subspace accelerated inexact Newton method for large scale wave functions calculations in Density Functional Theory

    SciTech Connect

    Fattebert, J

    2008-07-29

    We describe an iterative algorithm to solve electronic structure problems in Density Functional Theory. The approach is presented as a Subspace Accelerated Inexact Newton (SAIN) solver for the non-linear Kohn-Sham equations. It is related to a class of iterative algorithms known as RMM-DIIS in the electronic structure community. The method is illustrated with examples of real applications using a finite difference discretization and multigrid preconditioning.

  9. Reduction of Pulmonary Function After Surgical Lung Resections of Different Volume

    PubMed Central

    Cukic, Vesna

    2014-01-01

    Introduction: In recent years an increasing number of lung resections are being done because of the rising prevalence of lung cancer that occurs mainly in patients with limited lung function, what is caused with common etiologic factor - smoking cigarettes. Objective: To determine how big the loss of lung function is after surgical resection of lung of different range. Methods: The study was done on 58 patients operated at the Clinic for thoracic surgery KCU Sarajevo, previously treated at the Clinic for pulmonary diseases “Podhrastovi” in the period from 01.06.2012. to 01.06.2014. The following resections were done: pulmectomy (left, right), lobectomy (upper, lower: left and right). The values of postoperative pulmonary function were compared with preoperative ones. As a parameter of lung function we used FEV1 (forced expiratory volume in one second), and changes in FEV1 are expressed in liters and in percentage of the recorded preoperative and normal values of FEV1. Measurements of lung function were performed seven days before and 2 months after surgery. Results: Postoperative FEV1 was decreased compared to preoperative values. After pulmectomy the maximum reduction of FEV1 was 44%, and after lobectomy it was 22% of the preoperative values. Conclusion: Patients with airway obstruction are limited in their daily life before the surgery, and an additional loss of lung tissue after resection contributes to their inability. Potential benefits of lung resection surgery should be balanced in relation to postoperative morbidity and mortality. PMID:25568542

  10. LINKING LUNG AIRWAY STRUCTURE TO PULMONARY FUNCTION VIA COMPOSITE BRIDGE REGRESSION

    PubMed Central

    Chen, Kun; Hoffman, Eric A.; Seetharaman, Indu; Jiao, Feiran; Lin, Ching-Long; Chan, Kung-Sik

    2017-01-01

    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. PMID

  11. Clinical value of CT-based preoperative software assisted lung lobe volumetry for predicting postoperative pulmonary function after lung surgery

    NASA Astrophysics Data System (ADS)

    Wormanns, Dag; Beyer, Florian; Hoffknecht, Petra; Dicken, Volker; Kuhnigk, Jan-Martin; Lange, Tobias; Thomas, Michael; Heindel, Walter

    2005-04-01

    This study was aimed to evaluate a morphology-based approach for prediction of postoperative forced expiratory volume in one second (FEV1) after lung resection from preoperative CT scans. Fifteen Patients with surgically treated (lobectomy or pneumonectomy) bronchogenic carcinoma were enrolled in the study. A preoperative chest CT and pulmonary function tests before and after surgery were performed. CT scans were analyzed by prototype software: automated segmentation and volumetry of lung lobes was performed with minimal user interaction. Determined volumes of different lung lobes were used to predict postoperative FEV1 as percentage of the preoperative values. Predicted FEV1 values were compared to the observed postoperative values as standard of reference. Patients underwent lobectomy in twelve cases (6 upper lobes; 1 middle lobe; 5 lower lobes; 6 right side; 6 left side) and pneumonectomy in three cases. Automated calculation of predicted postoperative lung function was successful in all cases. Predicted FEV1 ranged from 54% to 95% (mean 75% +/- 11%) of the preoperative values. Two cases with obviously erroneous LFT were excluded from analysis. Mean error of predicted FEV1 was 20 +/- 160 ml, indicating absence of systematic error; mean absolute error was 7.4 +/- 3.3% respective 137 +/- 77 ml/s. The 200 ml reproducibility criterion for FEV1 was met in 11 of 13 cases (85%). In conclusion, software-assisted prediction of postoperative lung function yielded a clinically acceptable agreement with the observed postoperative values. This method might add useful information for evaluation of functional operability of patients with lung cancer.

  12. [The effect of lung diminishing interventions on immediate postoperative lung function and their modification by various forms of analgesia].

    PubMed

    Horch, R; Krönung, G; Westhofen, P; Giebel, G D

    1990-01-01

    The influence of different lung resection methods on pulmonary function was studied in 34 patients suffering from bronchial carcinoma. Daily measurements from the 1st to 10th postoperative day reveal the greatest losses of function after right upper lobectomy. Lower lobectomies or left upper lobectomy resulted in a less extensive loss of function. Recovery of function mainly occurs in the first 4 days after operation. Centrally acting analgetics are followed by a loss in pulmonary function whereas locally applied analgetics improve early postoperative function.

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

    PubMed Central

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

    2012-01-01

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

  14. Longitudinal lung function decline and wood dust exposure in the furniture industry.

    PubMed

    Jacobsen, G; Schlünssen, V; Schaumburg, I; Taudorf, E; Sigsgaard, T

    2008-02-01

    The aim of the present study was to investigate the relationship between change in lung function and cumulative exposure to wood dust. In total, 1,112 woodworkers (927 males, 185 females) and 235 reference workers (104 males, 185 females) participated in a 6-yr longitudinal study. Forced expiratory volume in one second (FEV(1)), forced vital capacity (FVC), height and weight were measured, and questionnaire data on respiratory symptoms, wood dust exposure and smoking habits were collected. Cumulative inhalable wood dust exposure was assessed using a study-specific job exposure matrix and exposure time. The median (range) for cumulative wood dust exposure was 3.75 (0-7.55) mg x year x m(-3). A dose-response relationship between cumulative wood dust exposure and percent annual decrease in FEV(1) was suggested for female workers. This was confirmed in a linear regression model adjusted for confounders, including smoking, height and age. An additional difference of -14.50 mL x yr(-1) and -27.97 mL x yr(-1) was revealed for females exposed to 3.75-4.71 mg x yr x m(-3) or to >4.71 mg x yr x m(-3), respectively, compared with non-/low-exposed females. For females, a positive trend between wood dust exposure and the cumulative incidence proportion of FEV(1)/FVC <70% was suggested. In conclusion, in the present low-exposed cohort, female woodworkers had an accelerated decline in lung function, which may be clinically relevant.

  15. Exposure assessment and lung function in pig and poultry farmers

    PubMed Central

    Radon, K; Weber, C; Iversen, M; Danuser, B; Pedersen, S; Nowak, D

    2001-01-01

    OBJECTIVES—To describe the relation between spirometric findings and farming characteristics and variables of exposure to organic dust measured during work in animal buildings. Farmers have traditionally been described as having one of the most dangerous occupations, so a large scale study on European farmers was carried out. This is the report of the second part of that study.
METHODS—40 pig farmers in Denmark and 36 poultry farmers in Switzerland were chosen randomly and were assessed over 1 working day.
RESULTS—Mean (SD) baseline spirometric results in pig farmers were higher than in poultry farmers (forced expiratory volume in 1 second (FEV1) (% of reference value) 108.3 (16.7) v 100.2 (14.2); p=0.04). Baseline lung function results were significantly associated with ventilation of the animal houses. Furthermore, temperature was related to spirometric findings in pig farmers.
CONCLUSIONS—Ventilation of the animal house and temperature might influence respiratory morbidity in farmers.


Keywords: ventilation; micro-organism; European multicentre study PMID:11351057

  16. Secreted Phosphoprotein 1 Is a Determinant of Lung Function Development in Mice

    PubMed Central

    Martin, Timothy M.; Concel, Vincent J.; Upadhyay, Swapna; Bein, Kiflai; Brant, Kelly A.; George, Leema; Mitra, Ankita; Thimraj, Tania A.; Fabisiak, James P.; Vuga, Louis J.; Fattman, Cheryl; Kaminski, Naftali; Schulz, Holger; Leikauf, George D.

    2014-01-01

    Secreted phosphoprotein 1 (Spp1) is located within quantitative trait loci associated with lung function that was previously identified by contrasting C3H/HeJ and JF1/Msf mouse strains that have extremely divergent lung function. JF1/Msf mice with diminished lung function had reduced lung SPP1 transcript and protein during the peak stage of alveologenesis (postnatal day [P]14–P28) as compared with C3H/HeJ mice. In addition to a previously identified genetic variant that altered runt-related transcription factor 2 (RUNX2) binding in the Spp1 promoter, we identified another promoter variant in a putative RUNX2 binding site that increased the DNA protein binding. SPP1 induced dose-dependent mouse lung epithelial-15 cell proliferation. Spp1(−/−) mice have decreased specific total lung capacity/body weight, higher specific compliance, and increased mean airspace chord length (Lm) compared with Spp1(+/+) mice. Microarray analysis revealed enriched gene ontogeny categories, with numerous genes associated with lung development and/or respiratory disease. Insulin-like growth factor 1, Hedgehog-interacting protein, wingless-related mouse mammary tumor virus integration site 5A, and NOTCH1 transcripts decreased in the lung of P14 Spp1(−/−) mice as determined by quantitative RT-PCR analysis. SPP1 promotes pneumocyte growth, and mice lacking SPP1 have smaller, more compliant lungs with enlarged airspace (i.e., increased Lm). Microarray analysis suggests a dysregulation of key lung developmental transcripts in gene-targeted Spp1(−/−) mice, particularly during the peak phase of alveologenesis. In addition to its known roles in lung disease, this study supports SPP1 as a determinant of lung development in mice. PMID:24816281

  17. TAZ contributes to pulmonary fibrosis by activating profibrotic functions of lung fibroblasts

    PubMed Central

    Noguchi, Satoshi; Saito, Akira; Mikami, Yu; Urushiyama, Hirokazu; Horie, Masafumi; Matsuzaki, Hirotaka; Takeshima, Hideyuki; Makita, Kosuke; Miyashita, Naoya; Mitani, Akihisa; Jo, Taisuke; Yamauchi, Yasuhiro; Terasaki, Yasuhiro; Nagase, Takahide

    2017-01-01

    Transcriptional coactivator with PDZ-binding motif (TAZ) regulates a variety of biological processes. Nuclear translocation and activation of TAZ are regulated by multiple mechanisms, including actin cytoskeleton and mechanical forces. TAZ is involved in lung alveolarization during lung development and Taz-heterozygous mice are resistant to bleomycin-induced lung fibrosis. In this study, we explored the roles of TAZ in the pathogenesis of idiopathic pulmonary fibrosis (IPF) through histological analyses of human lung tissues and cell culture experiments. TAZ was highly expressed in the fibroblastic foci of lungs from patients with IPF. TAZ controlled myofibroblast marker expression, proliferation, migration, and matrix contraction in cultured lung fibroblasts. Importantly, actin stress fibers and nuclear accumulation of TAZ were more evident when cultured on a stiff matrix, suggesting a feedback mechanism to accelerate fibrotic responses. Gene expression profiling revealed TAZ-mediated regulation of connective tissue growth factor (CTGF) and type I collagen. Clinical relevance of TAZ-regulated gene signature was further assessed using publicly available transcriptome data. These findings suggest that TAZ is involved in the pathogenesis of IPF through multifaceted effects on lung fibroblasts. PMID:28195168

  18. Functional characterization of pulmonary neuroendocrine cells in lung development, injury, and tumorigenesis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Pulmonary neuroendocrine cells (PNECs) are proposed to be the first specialized cell type to appear in the lung, but their ontogeny remains obscure. Although studies of PNECs have suggested their involvement in a number of lung functions, neither their in vivo significance nor the molecular mechanis...

  19. Pulmonary Rehabilitation in Improving Lung Function in Patients With Locally Advanced Non-Small Cell Lung Cancer Undergoing Chemoradiation

    ClinicalTrials.gov

    2017-01-05

    Cachexia; Fatigue; Pulmonary Complications; Radiation Toxicity; Recurrent Non-small Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer

  20. H-1 Nuclear Magnetic Resonance Metabolomics Analysis Identifies Novel Urinary Biomarkers for Lung Function

    SciTech Connect

    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.

  1. Molecular mechanisms underlying variations in lung function: a systems genetics analysis

    PubMed Central

    Obeidat, Ma’en; Hao, Ke; Bossé, Yohan; Nickle, David C; Nie, Yunlong; Postma, Dirkje S; Laviolette, Michel; Sandford, Andrew J; Daley, Denise D; Hogg, James C; Elliott, W Mark; Fishbane, Nick; Timens, Wim; Hysi, Pirro G; Kaprio, Jaakko; Wilson, James F; Hui, Jennie; Rawal, Rajesh; Schulz, Holger; Stubbe, Beate; Hayward, Caroline; Polasek, Ozren; Järvelin, Marjo-Riitta; Zhao, Jing Hua; Jarvis, Deborah; Kähönen, Mika; Franceschini, Nora; North, Kari E; Loth, Daan W; Brusselle, Guy G; Smith, Albert Vernon; Gudnason, Vilmundur; Bartz, Traci M; Wilk, Jemma B; O’Connor, George T; Cassano, Patricia A; Tang, Wenbo; Wain, Louise V; Artigas, María Soler; Gharib, Sina A; Strachan, David P; Sin, Don D; Tobin, Martin D; London, Stephanie J; Hall, Ian P; Paré, Peter D

    2016-01-01

    Summary Background Lung function measures reflect the physiological state of the lung, and are essential to the diagnosis of chronic obstructive pulmonary disease (COPD). The SpiroMeta-CHARGE consortium undertook the largest genome-wide association study (GWAS) so far (n=48 201) for forced expiratory volume in 1 s (FEV1) and the ratio of FEV1 to forced vital capacity (FEV1/FVC) in the general population. The lung expression quantitative trait loci (eQTLs) study mapped the genetic architecture of gene expression in lung tissue from 1111 individuals. We used a systems genetics approach to identify single nucleotide polymorphisms (SNPs) associated with lung function that act as eQTLs and change the level of expression of their target genes in lung tissue; termed eSNPs. Methods The SpiroMeta-CHARGE GWAS results were integrated with lung eQTLs to map eSNPs and the genes and pathways underlying the associations in lung tissue. For comparison, a similar analysis was done in peripheral blood. The lung mRNA expression levels of the eSNP-regulated genes were tested for associations with lung function measures in 727 individuals. Additional analyses identified the pleiotropic effects of eSNPs from the published GWAS catalogue, and mapped enrichment in regulatory regions from the ENCODE project. Finally, the Connectivity Map database was used to identify potential therapeutics in silico that could reverse the COPD lung tissue gene signature. Findings SNPs associated with lung function measures were more likely to be eQTLs and vice versa. The integration mapped the specific genes underlying the GWAS signals in lung tissue. The eSNP-regulated genes were enriched for developmental and inflammatory pathways; by comparison, SNPs associated with lung function that were eQTLs in blood, but not in lung, were only involved in inflammatory pathways. Lung function eSNPs were enriched for regulatory elements and were over-represented among genes showing differential expression during

  2. Passive expiration as a test of lung function.

    PubMed Central

    Ashutosh, K; Keighley, J F

    1978-01-01

    Twenty-five normal subjects, 14 non-smokers and 11 smokers, passively expired into a spirometer after a maximal active inspiration, and after a passive inflation of the chest by a pressure cycled intermittent positive-pressure breathing (IPPB) machine. Acceptable passive expirations could be performed by all subjects after a passive inspiration but by only 12 after an active inspiration. Expired volume was found to change exponentially with time (r greater than 0.98), and the time constant of passive expiration (Tp) was obtained. There was no significant difference between the smokers and non-smokers in age, sex, forced vital capacity, FEV1 FEV1/FVC%, maximum mid-expiratory flow rate, maximum expiratory flow at 50% and 25% of the vital capacity, or the magnitude of the fall in the dynamic compliance with increasing frequency of breathing (Cdyn/f). Tp in smokers (1.06 +/- 0.47 SD) was significantly longer than in the non-smokers (0.65 +/- 0.25 SD P less than 0.02). Tp had a significant correlation with Cdyn/f(Tp = 0.6 + 161.81 Cdyn/f +/- 0.38 SE, r = 0.49, P less than 0.02). We conclude that satisfactory passive expiratory spirograms can be easily obtained after a mechanically assisted passive inspiration. Tp thus obtained is determined by the intrinsic properties of the respiratory system (lung plus thorax), and is significantly prolonged in smokers compared with non-smokers when other studies of pulmonary function including frequency dependence of compliance are unchanged. PMID:371059

  3. Ex vivo lung perfusion to improve donor lung function and increase the number of organs available for transplantation.

    PubMed

    Valenza, Franco; Rosso, Lorenzo; Coppola, Silvia; Froio, Sara; Palleschi, Alessandro; Tosi, Davide; Mendogni, Paolo; Salice, Valentina; Ruggeri, Giulia M; Fumagalli, Jacopo; Villa, Alessandro; Nosotti, Mario; Santambrogio, Luigi; Gattinoni, Luciano

    2014-06-01

    This paper describes the initial clinical experience of ex vivo lung perfusion (EVLP) at the Fondazione Ca' Granda in Milan between January 2011 and May 2013. EVLP was considered if donor PaO2 /FiO2 was below 300 mmHg or if lung function was doubtful. Donors with massive lung contusion, aspiration, purulent secretions, pneumonia, or sepsis were excluded. EVLP was run with a low-flow, open atrium and low hematocrit technique. Thirty-five lung transplants from brain death donors were performed, seven of which after EVLP. EVLP donors were older (54 ± 9 years vs. 40 ± 15 years, EVLP versus Standard, P < 0.05), had lower PaO2 /FiO2 (264 ± 78 mmHg vs. 453 ± 119 mmHg, P < 0.05), and more chest X-ray abnormalities (P < 0.05). EVLP recipients were more often admitted to intensive care unit as urgent cases (57% vs. 18%, P = 0.05); lung allocation score at transplantation was higher (79 [40-84] vs. 39 [36-46], P < 0.05). After transplantation, primary graft dysfunction (PGD72 grade 3, 32% vs. 28%, EVLP versus Standard, P = 1), mortality at 30 days (0% vs. 0%, P = 1), and overall survival (71% vs. 86%, EVLP versus Standard P = 0.27) were not different between groups. EVLP enabled a 20% increase in available donor organs and resulted in successful transplants with lungs that would have otherwise been rejected (ClinicalTrials.gov number: NCT01967953).

  4. Ex vivo lung perfusion to improve donor lung function and increase the number of organs available for transplantation

    PubMed Central

    Valenza, Franco; Rosso, Lorenzo; Coppola, Silvia; Froio, Sara; Palleschi, Alessandro; Tosi, Davide; Mendogni, Paolo; Salice, Valentina; Ruggeri, Giulia M; Fumagalli, Jacopo; Villa, Alessandro; Nosotti, Mario; Santambrogio, Luigi; Gattinoni, Luciano

    2014-01-01

    This paper describes the initial clinical experience of ex vivo lung perfusion (EVLP) at the Fondazione Ca’ Granda in Milan between January 2011 and May 2013. EVLP was considered if donor PaO2/FiO2 was below 300 mmHg or if lung function was doubtful. Donors with massive lung contusion, aspiration, purulent secretions, pneumonia, or sepsis were excluded. EVLP was run with a low-flow, open atrium and low hematocrit technique. Thirty-five lung transplants from brain death donors were performed, seven of which after EVLP. EVLP donors were older (54 ± 9 years vs. 40 ± 15 years, EVLP versus Standard, P < 0.05), had lower PaO2/FiO2 (264 ± 78 mmHg vs. 453 ± 119 mmHg, P < 0.05), and more chest X-ray abnormalities (P < 0.05). EVLP recipients were more often admitted to intensive care unit as urgent cases (57% vs. 18%, P = 0.05); lung allocation score at transplantation was higher (79 [40–84] vs. 39 [36–46], P < 0.05). After transplantation, primary graft dysfunction (PGD72 grade 3, 32% vs. 28%, EVLP versus Standard, P = 1), mortality at 30 days (0% vs. 0%, P = 1), and overall survival (71% vs. 86%, EVLP versus Standard P = 0.27) were not different between groups. EVLP enabled a 20% increase in available donor organs and resulted in successful transplants with lungs that would have otherwise been rejected (ClinicalTrials.gov number: NCT01967953). PMID:24628890

  5. Acceleration of Lung Regeneration by Platelet-Rich Plasma Extract through the Low-Density Lipoprotein Receptor-Related Protein 5-Tie2 Pathway.

    PubMed

    Mammoto, Tadanori; Chen, Zhao; Jiang, Amanda; Jiang, Elisabeth; Ingber, Donald E; Mammoto, Akiko

    2016-01-01

    Angiogenesis, the growth of new blood vessels, plays a key role in organ development, homeostasis, and regeneration. The cooperation of multiple angiogenic factors, rather than a single factor, is required for physiological angiogenesis. Recently, we have reported that soluble platelet-rich plasma (PRP) extract, which contains abundant angiopoietin-1 and multiple other angiogenic factors, stimulates angiogenesis and maintains vascular integrity in vitro and in vivo. In this report, we have demonstrated that mouse PRP extract increases phosphorylation levels of the Wnt coreceptor low-density lipoprotein receptor-related protein 5 (LRP5) and thereby activates angiogenic factor receptor Tie2 in endothelial cells (ECs) and accelerates EC sprouting and lung epithelial cell budding in vitro. PRP extract also increases phosphorylation levels of Tie2 in the mouse lungs and accelerates compensatory lung growth and recovery of exercise capacity after unilateral pneumonectomy in mice, whereas soluble Tie2 receptor or Lrp5 knockdown attenuates the effects of PRP extract. Because human PRP extract is generated from autologous peripheral blood and can be stored at -80°C, our findings may lead to the development of novel therapeutic interventions for various angiogenesis-related lung diseases and to the improvement of strategies for lung regeneration.

  6. Mechanical Forces Accelerate Collagen Digestion by Bacterial Collagenase in Lung Tissue Strips

    PubMed Central

    Yi, Eunice; Sato, Susumu; Takahashi, Ayuko; Parameswaran, Harikrishnan; Blute, Todd A.; Bartolák-Suki, Erzsébet; Suki, Béla

    2016-01-01

    Most tissues in the body are under mechanical tension, and while enzymes mediate many cellular and extracellular processes, the effects of mechanical forces on enzyme reactions in the native extracellular matrix (ECM) are not fully understood. We hypothesized that physiological levels of mechanical forces are capable of modifying the activity of collagenase, a key remodeling enzyme of the ECM. To test this, lung tissue Young's modulus and a nonlinearity index characterizing the shape of the stress-strain curve were measured in the presence of bacterial collagenase under static uniaxial strain of 0, 20, 40, and 80%, as well as during cyclic mechanical loading with strain amplitudes of ±10 or ±20% superimposed on 40% static strain, and frequencies of 0.1 or 1 Hz. Confocal and electron microscopy was used to determine and quantify changes in ECM structure. Generally, mechanical loading increased the effects of enzyme activity characterized by an irreversible decline in stiffness and tissue deterioration seen on both confocal and electron microscopic images. However, a static strain of 20% provided protection against digestion compared to both higher and lower strains. The decline in stiffness during digestion positively correlated with the increase in equivalent alveolar diameters and negatively correlated with the nonlinearity index. These results suggest that the decline in stiffness results from rupture of collagen followed by load transfer and subsequent rupture of alveolar walls. This study may provide new understanding of the role of collagen degradation in general tissue remodeling and disease progression. PMID:27462275

  7. Mechanical Forces Accelerate Collagen Digestion by Bacterial Collagenase in Lung Tissue Strips.

    PubMed

    Yi, Eunice; Sato, Susumu; Takahashi, Ayuko; Parameswaran, Harikrishnan; Blute, Todd A; Bartolák-Suki, Erzsébet; Suki, Béla

    2016-01-01

    Most tissues in the body are under mechanical tension, and while enzymes mediate many cellular and extracellular processes, the effects of mechanical forces on enzyme reactions in the native extracellular matrix (ECM) are not fully understood. We hypothesized that physiological levels of mechanical forces are capable of modifying the activity of collagenase, a key remodeling enzyme of the ECM. To test this, lung tissue Young's modulus and a nonlinearity index characterizing the shape of the stress-strain curve were measured in the presence of bacterial collagenase under static uniaxial strain of 0, 20, 40, and 80%, as well as during cyclic mechanical loading with strain amplitudes of ±10 or ±20% superimposed on 40% static strain, and frequencies of 0.1 or 1 Hz. Confocal and electron microscopy was used to determine and quantify changes in ECM structure. Generally, mechanical loading increased the effects of enzyme activity characterized by an irreversible decline in stiffness and tissue deterioration seen on both confocal and electron microscopic images. However, a static strain of 20% provided protection against digestion compared to both higher and lower strains. The decline in stiffness during digestion positively correlated with the increase in equivalent alveolar diameters and negatively correlated with the nonlinearity index. These results suggest that the decline in stiffness results from rupture of collagen followed by load transfer and subsequent rupture of alveolar walls. This study may provide new understanding of the role of collagen degradation in general tissue remodeling and disease progression.

  8. NFE2L2 pathway polymorphisms and lung function decline in chronic obstructive pulmonary disease.

    PubMed

    Sandford, Andrew J; Malhotra, Deepti; Boezen, H Marike; Siedlinski, Mateusz; Postma, Dirkje S; Wong, Vivien; Akhabir, Loubna; He, Jian-Qing; Connett, John E; Anthonisen, Nicholas R; Paré, Peter D; Biswal, Shyam

    2012-08-01

    An oxidant-antioxidant imbalance in the lung contributes to the development of chronic obstructive pulmonary disease (COPD) that is caused by a complex interaction of genetic and environmental risk factors. Nuclear erythroid 2-related factor 2 (NFE2L2 or NRF2) is a critical molecule in the lung's defense mechanism against oxidants. We investigated whether polymorphisms in the NFE2L2 pathway affected the rate of decline of lung function in smokers from the Lung Health Study (LHS)(n = 547) and in a replication set, the Vlagtwedde-Vlaardingen cohort (n = 533). We selected polymorphisms in NFE2L2 in genes that positively or negatively regulate NFE2L2 transcriptional activity and in genes that are regulated by NFE2L2. Polymorphisms in 11 genes were significantly associated with rate of lung function decline in the LHS. One of these polymorphisms, rs11085735 in the KEAP1 gene, was previously shown to be associated with the level of lung function in the Vlagtwedde-Vlaardingen cohort but not with decline of lung function. Of the 23 associated polymorphisms in the LHS, only rs634534 in the FOSL1 gene showed a significant association in the Vlagtwedde-Vlaardingen cohort with rate of lung function decline, but the direction of the association was not consistent with that in the LHS. In summary, despite finding several nominally significant polymorphisms in the LHS, none of these associations were replicated in the Vlagtwedde-Vlaardingen cohort, indicating lack of effect of polymorphisms in the NFE2L2 pathway on the rate of decline of lung function.

  9. Asthma phenotypes modify the impact of environmetnal factors on lung function

    EPA Science Inventory

    Previous studies have examined the role of childhood asthma phenotypes based on clinical history on asthma severity and symptom aggravation by environmental risk factors. The current study focuses on the associations between lung function in childhood and environmental factors an...

  10. Lung function in asbestos-exposed workers, a systematic review and meta-analysis

    PubMed Central

    2011-01-01

    Background A continuing controversy exists about whether, asbestos exposure is associated with significant lung function impairments when major radiological abnormalities are lacking. We conducted a systematic review and meta-analysis in order to assess whether asbestos exposure is related to impairment of lung function parameters independently of the radiological findings. Methods MEDLINE was searched from its inception up to April 2010. We included studies that assessed lung function parameters in asbestos exposed workers and stratified subjects according to radiological findings. Estimates of VC, FEV1 and FEV1/VC with their dispersion measures were extracted and pooled. Results Our meta-analysis with data from 9,921 workers exposed to asbestos demonstrates a statistically significant reduction in VC, FEV1 and FEV1/VC, even in those workers without radiological changes. Less severe lung function impairments are detected if the diagnoses are based on (high resolution) computed tomography rather than the less sensitive X-ray images. The degree of lung function impairment was partly related to the proportion of smokers included in the studies. Conclusions Asbestos exposure is related to restrictive and obstructive lung function impairment. Even in the absence of radiological evidence of parenchymal or pleural diseases there is a trend for functional impairment. PMID:21791077

  11. Can infant lung function predict respiratory morbidity during the first year of life in preterm infants?

    PubMed

    Proietti, Elena; Riedel, Thomas; Fuchs, Oliver; Pramana, Isabelle; Singer, Florian; Schmidt, Anne; Kuehni, Claudia; Latzin, Philipp; Frey, Urs

    2014-06-01

    Compared with term-born infants, preterm infants have increased respiratory morbidity in the first year of life. We investigated whether lung function tests performed near term predict subsequent respiratory morbidity during the first year of life and compared this to standard clinical parameters in preterms. The prospective birth cohort included randomly selected preterm infants with and without bronchopulmonary dysplasia. Lung function (tidal breathing and multiple-breath washout) was measured at 44 weeks post-menstrual age during natural sleep. We assessed respiratory morbidity (wheeze, hospitalisation, inhalation and home oxygen therapy) after 1 year using a standardised questionnaire. We first assessed the association between lung function and subsequent respiratory morbidity. Secondly, we compared the predictive power of standard clinical predictors with and without lung function data. In 166 preterm infants, tidal volume, time to peak tidal expiratory flow/expiratory time ratio and respiratory rate were significantly associated with subsequent wheeze. In comparison with standard clinical predictors, lung function did not improve the prediction of later respiratory morbidity in an individual child. Although associated with later wheeze, noninvasive infant lung function shows large physiological variability and does not add to clinically relevant risk prediction for subsequent respiratory morbidity in an individual preterm.

  12. Respiratory symptoms and lung function in oil mist-exposed workers

    SciTech Connect

    Jarvholm, B.; Bake, B.; Lavenius, B.; Thiringer, G.; Vokmann, R.

    1982-06-01

    The prevalence of respiratory symptoms was registered and ventilatory function was determined in 164 men exposed to oil mist. The average exposure time was 16.2 years. One hundred fifty-nine office workers served as controls. The exposed men reported more respiratory symptoms: 14% of the exposed nonsmokers v. 2% of the nonsmoking controls having cough at least three months a year. There were non significant differences between spirometric measurements and chest roentgenograms of the men exposed to oil mist and those of the office workers. The lung function of 25 nonsmoking exposed men was further examined with other lung function tests. The mean values for closing volume, slope of the alveolar plateau, total lung capacity, residual volume, elastic recoil at various lung volumes, and diffusion capacity did not differ significantly.

  13. Scale dependence of structure-function relationship in the emphysematous mouse lung

    PubMed Central

    Sato, Susumu; Bartolák-Suki, Erzsébet; Parameswaran, Harikrishnan; Hamakawa, Hiroshi; Suki, Béla

    2015-01-01

    The purpose of this study was to determine how the initial distribution of elastase in mouse lungs determines the time course of tissue destruction and how structural heterogeneity at different spatial scales influences lung function. We evaluated lung function and alveolar structure in normal and emphysematous C57BL/6 mice at 2 and 21 days following orotracheal treatment with porcine pancreatic elastase (PPE). Initial distribution of elastase 1 h after treatment was assessed using red fluorescently labeled PPE (f-PPE) by laser scanning confocal microscopy. From measured input impedance of the respiratory system, the global lung compliance, and the variability of regional compliance were obtained. Lungs were fixed and equivalent airspace diameters were measured in four lobes of the right lung and three regions of the left lung. At day 2 and day 21, the mean airspace diameter of each region was significantly enlarged which was accompanied by an increased inter-regional heterogeneity. The deposition of f-PPE on day 0 was much more heterogeneous than the inter-regional diameters at both day 2 and day 21 and, at day 21, this reached statistical significance (p < 0.05). Microscale heterogeneity characterized by the overall variability of airspace diameters correlated significantly better with compliance than macroscale or inter-regional heterogeneity. Furthermore, while the spatial distribution of the inflammatory response does not seem to follow that of the elastase deposition, it correlates with the strongest regional determinant of lung function. These results may help interpret lung function decline in terms of structural deterioration in human patients with emphysema. PMID:26029115

  14. Scale dependence of structure-function relationship in the emphysematous mouse lung.

    PubMed

    Sato, Susumu; Bartolák-Suki, Erzsébet; Parameswaran, Harikrishnan; Hamakawa, Hiroshi; Suki, Béla

    2015-01-01

    The purpose of this study was to determine how the initial distribution of elastase in mouse lungs determines the time course of tissue destruction and how structural heterogeneity at different spatial scales influences lung function. We evaluated lung function and alveolar structure in normal and emphysematous C57BL/6 mice at 2 and 21 days following orotracheal treatment with porcine pancreatic elastase (PPE). Initial distribution of elastase 1 h after treatment was assessed using red fluorescently labeled PPE (f-PPE) by laser scanning confocal microscopy. From measured input impedance of the respiratory system, the global lung compliance, and the variability of regional compliance were obtained. Lungs were fixed and equivalent airspace diameters were measured in four lobes of the right lung and three regions of the left lung. At day 2 and day 21, the mean airspace diameter of each region was significantly enlarged which was accompanied by an increased inter-regional heterogeneity. The deposition of f-PPE on day 0 was much more heterogeneous than the inter-regional diameters at both day 2 and day 21 and, at day 21, this reached statistical significance (p < 0.05). Microscale heterogeneity characterized by the overall variability of airspace diameters correlated significantly better with compliance than macroscale or inter-regional heterogeneity. Furthermore, while the spatial distribution of the inflammatory response does not seem to follow that of the elastase deposition, it correlates with the strongest regional determinant of lung function. These results may help interpret lung function decline in terms of structural deterioration in human patients with emphysema.

  15. Influence of Body Composition on Lung Function and Respiratory Muscle Strength in Children With Obesity

    PubMed Central

    Costa Junior, Dirceu; Peixoto-Souza, Fabiana S.; Araujo, Poliane N.; Barbalho-Moulin, Marcela C.; Alves, Viviane C.; Gomes, Evelim L. F. D.; Costa, Dirceu

    2016-01-01

    Background Obesity affects lung function and respiratory muscle strength. The aim of the present study was to assess lung function and respiratory muscle strength in children with obesity and determine the influence of body composition on these variables. Methods A cross-sectional study was conducted involving 75 children (40 with obesity and 35 within the ideal weight range) aged 6 - 10 years. Body mass index, z score, waist circumference, body composition (tetrapolar bioimpedance), respiratory muscle strength and lung function (spirometry) were evaluated. Results Children with obesity exhibited larger quantities of both lean and fat mass in comparison to those in the ideal weight range. No significant differences were found between groups regarding the respective reference values for respiratory muscle strength. Male children with obesity demonstrated significantly lower lung function values (forced expiratory volume in the first second % (FEV1%) and FEV1/forced vital capacity % (FVC%) : 93.76 ± 9.78 and 92.29 ± 3.8, respectively) in comparison to males in the ideal weight range (99.87 ± 9.72 and 96.31 ± 4.82, respectively). The regression models demonstrated that the spirometric variables were influenced by all body composition variables. Conclusion Children with obesity demonstrated a reduction in lung volume and capacity. Thus, anthropometric and body composition characteristics may be predictive factors for altered lung function. PMID:26767078

  16. Dietary factors and lung function in the general population: wine and resveratrol intake.

    PubMed

    Siedlinski, M; Boer, J M A; Smit, H A; Postma, D S; Boezen, H M

    2012-02-01

    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 impact of wine and resveratrol intake, and SIRT1 single-nucleotide polymorphisms (SNPs) on lung function in the general population. Effects of red and white wine and resveratrol intake on forced expiratory volume in 1 s (FEV(1)), forced vital capacity (FVC) and FEV(1)/FVC were analysed in the population-based Doetinchem cohort (n=3,224). Associations of four tagging SIRT1 SNPs with lung function were analysed in the Doetinchem (n=1,152) and Vlagtwedde-Vlaardingen (n=1,390) cohorts. Resveratrol intake was associated with higher FVC levels, and white wine intake with higher FEV(1) levels and lower risk of airway obstruction. SIRT1 SNPs were not significantly associated with level or course of lung function, either directly or indirectly via wine or resveratrol intake. This study shows a positive association of resveratrol intake with lung function in the general population, confirms the previously reported positive association of white wine intake with higher levels of FEV(1), and additionally shows an association with a higher FEV(1)/FVC ratio. These effects probably do not run via SNPs in SIRT1.

  17. Leukemia Inhibitory Factor in Rat Fetal Lung Development: Expression and Functional Studies

    PubMed Central

    Nogueira-Silva, Cristina; Piairo, Paulina; Carvalho-Dias, Emanuel; Peixoto, Francisca O.; Moura, Rute S.; Correia-Pinto, Jorge

    2012-01-01

    Background Leukemia inhibitory factor (LIF) and interleukin-6 (IL-6) are members of the family of the glycoprotein 130 (gp130)-type cytokines. These cytokines share gp130 as a common signal transducer, which explains why they show some functional redundancy. Recently, it was demonstrated that IL-6 promotes fetal lung branching. Additionally, LIF has been implicated in developmental processes of some branching organs. Thus, in this study LIF expression pattern and its effects on fetal rat lung morphogenesis were assessed. Methodology/Principal Findings LIF and its subunit receptor LIFRα expression levels were evaluated by immunohistochemistry and western blot in fetal rat lungs of different gestational ages, ranging from 13.5 to 21.5 days post-conception. Throughout all gestational ages studied, LIF was constitutively expressed in pulmonary epithelium, whereas LIFRα was first mainly expressed in the mesenchyme, but after pseudoglandular stage it was also observed in epithelial cells. These results point to a LIF epithelium-mesenchyme cross-talk, which is known to be important for lung branching process. Regarding functional studies, fetal lung explants were cultured with increasing doses of LIF or LIF neutralizing antibodies during 4 days. MAPK, AKT, and STAT3 phosphorylation in the treated lung explants was analyzed. LIF supplementation significantly inhibited lung growth in spite of an increase in p44/42 phosphorylation. On the other hand, LIF inhibition significantly stimulated lung growth via p38 and Akt pathways. Conclusions/Significance The present study describes that LIF and its subunit receptor LIFRα are constitutively expressed during fetal lung development and that they have an inhibitory physiological role on fetal lung branching. PMID:22291973

  18. Changes in cystic fibrosis airway microbial community associated with a severe decline in lung function.

    PubMed

    Paganin, Patrizia; Fiscarelli, Ersilia Vita; Tuccio, Vanessa; Chiancianesi, Manuela; Bacci, Giovanni; Morelli, Patrizia; Dolce, Daniela; Dalmastri, Claudia; De Alessandri, Alessandra; Lucidi, Vincenzina; Taccetti, Giovanni; Mengoni, Alessio; Bevivino, Annamaria

    2015-01-01

    Cystic fibrosis (CF) is a genetic disease resulting in chronic polymicrobial infections of the airways and progressive decline in lung function. To gain insight into the underlying causes of severe lung diseases, we aimed at comparing the airway microbiota detected in sputum of CF patients with stable lung function (S) versus those with a substantial decline in lung function (SD). Microbiota composition was investigated by using culture-based and culture-independent methods, and by performing multivariate and statistical analyses. Culture-based methods identified some microbial species associated with a worse lung function, i.e. Pseudomonas aeruginosa, Rothia mucilaginosa, Streptococcus pneumoniae and Candida albicans, but only the presence of S. pneumoniae and R. mucilaginosa was found to be associated with increased severe decline in forced expiratory volume in 1 second (FEV1). Terminal-Restriction Fragment Length Polymorphism (T-RFLP) analysis revealed a higher bacterial diversity than that detected by culture-based methods. Molecular signatures with a statistically significant odds ratio for SD status were detected, and classified as Pseudomonas, Burkholderia and Shewanella, while for other Terminal Restriction Fragments (T-RFs) no species assignation was achieved. The analysis of T-RFLP data using ecological biodiversity indices showed reduced Evenness in SD patients compared to S ones, suggesting an impaired ecology of the bacterial community in SD patients. Statistically significant differences of the ecological biodiversity indices among the three sub-groups of FEV1 (normal/mild vs moderate vs severe) were also found, suggesting that the patients with moderate lung disease experienced changes in the airway assembly of taxa. Overall, changes in CF airway microbial community associated with a severe lung function decline were detected, allowing us to define some discriminatory species as well as some discriminatory T-RFs that represent good candidates for the

  19. Functionally dissimilar neighbors accelerate litter decomposition in two grass species.

    PubMed

    Barbe, Lou; Jung, Vincent; Prinzing, Andreas; Bittebiere, Anne-Kristel; Butenschoen, Olaf; Mony, Cendrine

    2017-02-16

    Plant litter decomposition is a key regulator of nutrient recycling. In a given environment, decomposition of litter from a focal species depends on its litter quality and on the efficiency of local decomposers. Both may be strongly modified by functional traits of neighboring species, but the consequences for decomposition of litter from the focal species remain unknown. We tested whether decomposition of a focal plant's litter is influenced by the functional-trait dissimilarity to the neighboring plants. We cultivated two grass species (Brachypodium pinnatum and Elytrigia repens) in experimental mesocosms with functionally similar and dissimilar neighborhoods, and reciprocally transplanted litter. For both species, litter quality increased in functionally dissimilar neighborhoods, partly as a result of changes in functional traits involved in plant-plant interactions. Furthermore, functional dissimilarity increased overall decomposer efficiency in one species, probably via complementarity effects. Our results suggest a novel mechanism of biodiversity effects on ecosystem functioning in grasslands: interspecific functional diversity within plant communities can enhance intraspecific contributions to litter decomposition. Thus, plant species might better perform in diverse communities by benefiting from higher remineralization rates of their own litter.

  20. Decline in lung function rather than baseline lung function is associated with the development of metabolic syndrome: A six-year longitudinal study

    PubMed Central

    Baek, Jong-Ha; Jee, Jae Hwan; Hur, Kyu Yeon; Lee, Moon-Kyu

    2017-01-01

    This study was conducted to investigate whether baseline lung function or change in lung function is associated with the development of metabolic syndrome (MS) in Koreans. We analyzed clinical and laboratory data from 3,768 Koreans aged 40–60 years who underwent medical check-ups over a six-year period between 2006 and 2012. We calculated the percent change in forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) over the study period. We tested for an association between baseline lung function or lung function change during the follow-up period and the development of MS. The 533 subjects (14.1%) developed MS after the six-year follow-up. The baseline FVC and FEV1 were not different between the subjects who developed MS after six years and the subject without MS after six years. The percent change in FVC over six years in subjects who developed MS after six years was higher than that in subjects who did not develop MS (-5.75 [-10.19 –-1.17], -3.29 [-7.69–1.09], respectively, P = 0.001). The percent change in FVC over six years was associated with MS development after adjusting for age, sex, body mass index (BMI), glucose, HDL, triglyceride, waist circumferences (WC), and systolic blood pressure. However, these association was not significant after adjusting for change of BMI and change of WC over six years (P = 0.306). The greater change in vital capacity over six years of follow-up was associated with MS development, predominantly due to obesity and abdominal obesity. The prospective study is needed to determine the relationship between lung function decline and MS. PMID:28346522

  1. Impact of video-assisted thoracoscopic major lung resection on immune function.

    PubMed

    Ng, Calvin S H; Wan, Innes Y P; Yim, Anthony P C

    2009-08-01

    Video-assisted thoracoscopic major lung resection for early stage non-small-cell lung carcinoma has been associated with less postoperative pain, better preserved pulmonary function, shorter hospital stay, and enhanced tolerance of adjuvant chemotherapy compared to thoracotomy. Initial concerns regarding safety, oncological clearance, and cost effectiveness were unfounded. Several recent trials have reported improved long-term survival in patients with early stage non-small-cell lung carcinoma undergoing video-assisted thoracoscopic major lung resection, compared to the open technique, although there are inconsistencies. Interestingly, the immune status and autologous tumor killing ability of lung cancer patients have previously been associated with long-term survival. Video-assisted thoracoscopic lung resection results in an attenuated postoperative inflammatory response, but more importantly, it better preserves postoperative immune function. Circulating natural killer and T-cell numbers, T-cell oxidative activity, and levels of immunochemokines such as insulin growth factor binding protein-3 are higher after video-assisted thoracoscopic surgery than after thoracotomy. Recently, interest has developed in the role of the angiogenesis factor, vascular endothelial growth factor, after cancer surgery. Whether differences in immunological and biochemical mediators contribute towards improved long-term survival following video-assisted thoracoscopic major lung resection for cancer remains to be confirmed.

  2. Functional drug-gene interactions in lung cancer.

    PubMed

    Smida, Michal; Nijman, Sebastian M B

    2012-04-01

    Despite the dawn of the genomic information era, the challenges of cancer treatment remain formidable. Particularly for the most prevalent cancer types, including lung cancer, successful treatment of metastatic disease is rare and escalating costs for modern targeted drugs place an increasing strain on healthcare systems. Although powerful diagnostic tools to characterize individual tumor samples in great molecular detail are becoming rapidly available, the transformation of this information into therapy provides a major challenge. A fundamental difficulty is the molecular complexity of cancer cells that often causes drug resistance, but can also render tumors exquisitely sensitive to targeted agents. By using lung cancer as an example, we outline the principles that govern drug sensitivity and resistance from a genetic perspective and discuss how in vitro chemical-genetic screens can impact on patient stratification in the clinic.

  3. Exhaled Nitric Oxide, Lung Function, and Exacerbations in Wheezy Infants and Toddlers

    PubMed Central

    Debley, Jason S.; Stamey, David C.; Cochrane, Elizabeth S.; Gama, Kim L.; Redding, Gregory J.

    2010-01-01

    Background There are limited data assessing the relationship between fractional concentration of exhaled nitric oxide (FENO) and lung function or exacerbations in infants with recurrent wheezing. Objectives In a longitudinal pilot study of children < 2 years old we assessed whether baseline FENO was associated with lung function, bronchodilator responsiveness, changes in lung function, or subsequent exacerbations of wheezing. Methods Forced expiratory flows and volumes using the raised-volume rapid thoracic compression method were measured in 44 infants and toddlers (mean age 15.7 mos.) with recurrent wheezing. Single-breath exhaled nitric oxide (SB-eNO) was measured at 50 mL/sec. Lung function was again measured 6 months after enrollment. Results At enrollment FEV0.5, FEF25-75, and FEF75 z-scores for the cohort were significantly less than zero. There was no correlation between enrollment SB-eNO and enrollment lung function measures. SB-eNO was higher in infants with bronchodilator responsiveness (46.1 vs. 23.6 ppb, p<0.001), and was associated with a decline in FEV0.5 (r = -.54, P = 0.001), FEF25-75 (r = -0.6, P < 0.001), and FEF75 (r = -0.55, P = 0.001) over 6 months. A 10ppb increase in SB-eNO was associated with a 0.4 z-score decline in FEV0.5, a 0.4 z-score decline in FEF25-75, and a 0.42 z-score decline in FEF75. SB-eNO was superior to lung function and bronchodilator responsivenss in predicting subsequent wheezing treated with systemic steroids. Conclusions SB-eNO may predict changes in lung function and risk of future wheezing, and holds promise as a biomarker to predict asthma in wheezy infants and toddlers. PMID:20462633

  4. [Role of functional imaging in the definition of target volumes for lung cancer radiotherapy].

    PubMed

    Thureau, S; Hapdey, S; Vera, P

    2016-10-01

    Functional imaging with positron emission tomography (PET) is interesting to optimize lung radiotherapy planning, and probably to deliver a heterogeneous dose or adapt the radiation dose during treatment. Only fluorodeoxyglucose (FDG) PET-computed tomography (CT) is validated for staging lung cancer and planning radiotherapy. The optimal segmentation methods remain to be defined as well as the interest of "dose painting" from pre-treatment PET (metabolism: FDG) or hypoxia (fluoromisonidazole: FMISO) and the interest of replanning based on pertherapeutic PET.

  5. Exogenous surfactant restores lung function but not peripheral immunosuppression in ventilated surfactant-deficient rats.

    PubMed

    Vreugdenhil, Harriet A; Lachmann, Burkhard; Haitsma, Jack J; Zijlstra, Jitske; Heijnen, Cobi J; Jansen, Nicolaas J; van Vught, Adrianus J

    2006-01-01

    The authors have previously shown that mechanical ventilation can result in increased pulmonary inflammation and suppressed peripheral leukocyte function. In the present study the effect of surfactant therapy on pulmonary inflammation and peripheral immune function in ventilated surfactant-deficient rats was assessed. Surfactant deficiency was induced by repeated lung lavage, treated rats with surfactant or left them untreated, and ventilated the rats during 2 hours. Nonventilated rats served as healthy control group. Expression of macrophage inflammatory protein (MIP)-2 was measured in bronchoalveolar lavage (BAL), interleukin (IL)-1beta, and heat shock protein 70 (HSP70) were measured in total lung homogenates. Outside the lung phytohemagglutinin (PHA)-induced lymphocyte proliferation, interferon (IFN)-gamma and IL-10 production, and natural killer activity were measured in splenocytes. After 2 hours of mechanical ventilation, expression of MIP-2, IL-1beta, and HSP70 increased significantly in the lungs of surfactant-deficient rats. Outside the lung, mitogen-induced proliferation and production of IFN-gamma and IL-10 reduced significantly. Only natural killer cell activity remained unaffected. Surfactant treatment significantly improved lung function, but could not prevent increased pulmonary expression of MIP-2, IL-1beta, and HSP70 and decreased peripheral mitogen-induced lymphocyte proliferation and IFN-gamma and IL-10 production in vitro. In conclusion, 2 hours of mechanical ventilation resulted in increased lung inflammation and partial peripheral leukocyte suppression in surfactant-deficient rats. Surfactant therapy ameliorated lung function but could not prevent or restore peripheral immunosuppression. The authors postulate that peripheral immunosuppression may occur in ventilated surfactant deficient patients, which may enhance susceptibility for infections.

  6. VARA attenuates hyperoxia-induced impaired alveolar development and lung function in newborn mice

    PubMed Central

    James, Masheika L.; Ross, A. Catharine; Nicola, Teodora; Steele, Chad

    2013-01-01

    We have recently shown that a combination of vitamin A (VA) and retinoic acid (RA) in a 10:1 molar ratio (VARA) synergistically increases lung retinoid content in newborn rodents, more than either VA or RA alone in equimolar amounts. We hypothesized that the increase in lung retinoids would reduce oxidative stress and proinflammatory cytokines, resulting in attenuation of alveolar simplification and abnormal lung function in hyperoxia-exposed newborn mice. Newborn C57BL/6 mice were exposed to 85% O2 (hyperoxia) or air (normoxia) for 7 or 14 days from birth and given vehicle or VARA every other day. Lung retinol content was measured by HPLC, function was assessed by flexiVent, and development was evaluated by radial alveolar counts, mean linear intercept, and secondary septal crest density. Mediators of oxidative stress, inflammation, and alveolar development were evaluated in lung homogenates. We observed that VARA increased lung retinol stores and attenuated hyperoxia-induced alveolar simplification while increasing lung compliance and lowering resistance. VARA attenuated hyperoxia-induced increases in DNA damage and protein oxidation accompanied with a reduction in nuclear factor (erythroid-derived 2)-like 2 protein but did not alter malondialdehyde adducts, nitrotyrosine, or myeloperoxidase concentrations. Interferon-γ and macrophage inflammatory protein-2α mRNA and protein increased with hyperoxia, and this increase was attenuated by VARA. Our study suggests that the VARA combination may be a potential therapeutic strategy in conditions characterized by VA deficiency and hyperoxia-induced lung injury during lung development, such as bronchopulmonary dysplasia in preterm infants. PMID:23585226

  7. Alveolar recruitment strategy during cardiopulmonary bypass does not improve postoperative gas exchange and lung function.

    PubMed

    Scherer, Mirela; Dettmer, Sebastian; Meininger, Dirk; Deschka, Heinz; Geyer, Galina; Regulla, Caroline; Moritz, Anton

    2009-03-01

    Pulmonary dysfunction with impairment of lung function and oxygenation is one of the most serious problems in the early postoperative period after cardiac surgery. In this study we investigated the effect of alveolar recruitment strategy during cardiopulmonary bypass on postoperative gas exchange and lung function. This prospective randomized study included 32 patients undergoing elective myocardial revascularization with cardiopulmonary bypass. In 16 patients 5 cm H(2)O of positive end-expiratory pressure was applied after intubation and maintained until extubation (Group I). In the other 16 patients (group II) a positive end expiratory pressure (PEEP) of 5 cm H(2)O was maintained as well but was increased to 14 cm H(2)O every 20 min for 2 min during cross clamp. Measurements were taken preoperatively, before skin incision, before and after (3, 24, 48 h) cardiopulmonary bypass and before discharge (6th postoperative day). Postoperative gas exchange, extravascular lung water and lung function showed no significant difference between the groups. Postoperative pulmonary function variables were lower in both groups compared to baseline values. In patients with normal preoperative pulmonary function, application of an alveolar recruitment strategy during cardiopulmonary bypass does not improve postoperative gas exchange and lung function after cardiac surgery.

  8. IMRT treatment plans and functional planning with functional lung imaging from 4D-CT for thoracic cancer patients

    PubMed Central

    2013-01-01

    Background and purpose Currently, the inhomogeneity of the pulmonary function is not considered when treatment plans are generated in thoracic cancer radiotherapy. This study evaluates the dose of treatment plans on highly-functional volumes and performs functional treatment planning by incorporation of ventilation data from 4D-CT. Materials and methods Eleven patients were included in this retrospective study. Ventilation was calculated using 4D-CT. Two treatment plans were generated for each case, the first one without the incorporation of the ventilation and the second with it. The dose of the first plans was overlapped with the ventilation and analyzed. Highly-functional regions were avoided in the second treatment plans. Results For small targets in the first plans (PTV < 400 cc, 6 cases), all V5, V20 and the mean lung dose values for the highly-functional regions were lower than that of the total lung. For large targets, two out of five cases had higher V5 and V20 values for the highly-functional regions. All the second plans were within constraints. Conclusion Radiation treatments affect functional lung more seriously in large tumor cases. With compromise of dose to other critical organs, functional treatment planning to reduce dose in highly-functional lung volumes can be achieved PMID:23281734

  9. Functional changes in systemic and regional (intracranial) circulation accompanying low accelerations

    NASA Technical Reports Server (NTRS)

    Usachev, V. V.; Shinkarevskaya, I. P.

    1973-01-01

    Functional changes in systemic and cerebral hemodynamics were studied with respect to vestibular stresses. The main types of responses, differing qualitatively with respect to the tolerance of test subjects to low accelerations (particularly to Coriolis accelerations), were established. This is of practical importance in the selection of aircraft and space pilots. The data presented sheds light on the physiological mechanisms of adaptation and disturbed compensation during vestibular stimulation. Further studies in this important field of aerospace medicine are outlined.

  10. Accelerating expansion or inhomogeneity? II. Mimicking acceleration with the energy function in the Lemaître-Tolman model

    NASA Astrophysics Data System (ADS)

    Krasiński, Andrzej

    2014-07-01

    This is a continuation of the paper published in Phys. Rev. D 89, 023520 (2014). Here we investigate how the luminosity distance-redshift relation DL(z) of the ΛCDM model is duplicated in the Lemaître-Tolman (L-T) model with Λ =0, constant bang-time function tB and the energy function E(r) mimicking accelerated expansion on the observer's past light cone (r is a uniquely defined comoving radial coordinate). Numerical experiments show that E>0 necessarily. The functions z(r) and E(r) are numerically calculated from the initial point at the observer's position, then backward from the initial point at the apparent horizon (AH). Reconciling the results of the two calculations allows one to determine the values of E/r2 at r=0 and at the AH. The problems connected with continuing the calculation through the AH are discussed in detail and solved. Then z(r) and E(r) are continued beyond the AH, up to the numerical crash that signals the contact of the light cone with the big bang. Similarly, the light cone of the L-T model is calculated by proceeding from the two initial points, and compared with the ΛCDM light cone. The model constructed here contains shell crossings, but they can be removed by matching the L-T region to a Friedmann background, without causing any conflict with the type Ia supernovae observations. The mechanism of imitating the accelerated expansion by the E(r) function is explained in a descriptive way.

  11. Evaluation of glucocorticoid receptor function in COPD lung macrophages using beclomethasone-17-monopropionate.

    PubMed

    Plumb, Jonathan; Robinson, Laura; Lea, Simon; Banyard, Antonia; Blaikley, John; Ray, David; Bizzi, Andrea; Volpi, Giorgina; Facchinetti, Fabrizio; Singh, Dave

    2013-01-01

    Previous studies of glucocorticoid receptor (GR) function in COPD lung macrophages have used dexamethasone to evaluate inhibition of cytokine production. We have now used the clinically relevant corticosteroid beclomethasone-17-monopropionate (17-BMP) to assess GR function in COPD lung macrophages, and investigated the transactivation of glucocorticoid sensitive genes and GR phosphorylation in addition to cytokine production. Lung macrophages were purified from surgically acquired lung tissue, from patients with COPD, smokers, and non-smokers. The transactivation of glucocorticoid sensitive genes (FKBP51 and GILZ) by 17-BMP were analysed by polymerase chain reaction. 17-BMP suppression of LPS-induced TNFα, IL-6 and CXCL8 was measured by ELISA and GR phosphorylation was measured by immunohistochemistry and Western blot. 17-BMP reduced cytokine release in a concentration dependent manner, with >70% inhibition of all cytokines, and no difference between COPD patients and controls. Similarly, the transactivation of FKBP51 and GILZ, and GR phosphorylation was similar between COPD patients and controls. In this context, GR function in COPD lung macrophages is unaltered. 17-BMP effectively suppresses cytokine production in COPD lung macrophages.

  12. Factors Associated with Worse Lung Function in Cystic Fibrosis Patients with Persistent Staphylococcus aureus

    PubMed Central

    den Reijer, Martijn; Wiedemann, Bärbel; Tümmler, Burkhard; Ellemunter, Helmut; Dübbers, Angelika; Küster, Peter; Ballmann, Manfred; Koerner-Rettberg, Cordula; Große-Onnebrink, Jörg; Heuer, Eberhardt; Sextro, Wolfgang; Mainz, Jochen G.; Hammermann, Jutta; Riethmüller, Joachim; Graepler-Mainka, Ute; Staab, Doris; Wollschläger, Bettina; Szczepanski, Rüdiger; Schuster, Antje; Tegtmeyer, Friedrich-Karl; Sutharsan, Sivagurunathan; Wald, Alexandra; Nofer, Jerzy-Roch; van Wamel, Willem; Becker, Karsten; Peters, Georg

    2016-01-01

    Background Staphylococcus aureus is an important pathogen in cystic fibrosis (CF). However, it is not clear which factors are associated with worse lung function in patients with persistent S. aureus airway cultures. Our main hypothesis was that patients with high S. aureus density in their respiratory specimens would more likely experience worsening of their lung disease than patients with low bacterial loads. Methods Therefore, we conducted an observational prospective longitudinal multi-center study and assessed the association between lung function and S. aureus bacterial density in respiratory samples, co-infection with other CF-pathogens, nasal S. aureus carriage, clinical status, antibiotic therapy, IL-6- and IgG-levels against S. aureus virulence factors. Results 195 patients from 17 centers were followed; each patient had an average of 7 visits. Data were analyzed using descriptive statistics and generalized linear mixed models. Our main hypothesis was only supported for patients providing throat specimens indicating that patients with higher density experienced a steeper lung function decline (p<0.001). Patients with exacerbations (n = 60), S. aureus small-colony variants (SCVs, n = 84) and co-infection with Stenotrophomonas maltophilia (n = 44) had worse lung function (p = 0.0068; p = 0.0011; p = 0.0103). Patients with SCVs were older (p = 0.0066) and more often treated with trimethoprim/sulfamethoxazole (p = 0.0078). IL-6 levels positively correlated with decreased lung function (p<0.001), S. aureus density in sputa (p = 0.0016), SCVs (p = 0.0209), exacerbations (p = 0.0041) and co-infections with S. maltophilia (p = 0.0195) or A. fumigatus (p = 0.0496). Conclusions In CF-patients with chronic S. aureus cultures, independent risk factors for worse lung function are high bacterial density in throat cultures, exacerbations, elevated IL-6 levels, presence of S. aureus SCVs and co-infection with S. maltophilia. Trial Registration ClinicalTrials.gov NCT

  13. Common SIRT1 variants modify the effect of abdominal adipose tissue on aging-related lung function decline.

    PubMed

    Curjuric, Ivan; Imboden, Medea; Bridevaux, Pierre-Olivier; Gerbase, Margaret W; Haun, Margot; Keidel, Dirk; Kumar, Ashish; Pons, Marco; Rochat, Thierry; Schikowski, Tamara; Schindler, Christian; von Eckardstein, Arnold; Kronenberg, Florian; Probst-Hensch, Nicole M

    2016-06-01

    Lung function is an independent predictor of mortality and serves as an aging marker in never smokers. The protein sirtuin-1 of gene SIRT1 has profound anti-inflammatory effects and regulates metabolic pathways. Its suggested longevity effects on lower organisms remain poorly studied in humans. In 1132 never smokers of the population-based SAPALDIA cohort, we investigated associations between single nucleotide polymorphisms (SNPs; rs730821, rs10997868, rs10823116) of SIRT1 and aging-related lung function decline over 11 years in terms of change in forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, and forced expiratory flow between 25 and 75 % of FVC (FEF25-75) using multiple linear regression models. Interactions between the SIRT1 SNPs and adiposity parameters (body mass index (BMI), its change and weight gain) were tested by including multiplicative interaction terms into the models. SIRT1 polymorphisms exhibited no main effects, but modified the association between obesity measures and FEV1/FVC and FEF25-75 decline (p = 0.009-0.046). Per risk allele, FEV1/FVC decline was accelerated up to -0.5 % (95 % CI -1.0 to 0 %) and -0.7 % (-1.3 to -0.2 %) over interquartile range increases in BMI (2.4 kg/m(2)) or weight (6.5 kg), respectively. For FEF25-75 decline, corresponding estimates were -57 mL/s (-117 to 4 mL/s) and -76 mL/s (-1429 to -9 mL/s). Interactions were not present in participants with genetically lowered C-reactive protein concentrations. Genetic variation in SIRT1 might therefore affect lung function and human longevity by modifying subclinical inflammation arising from abdominal adipose tissue.

  14. Plasma carbonyls do not correlate with lung function or computed tomography measures of lung density in older smokers

    PubMed Central

    Mesia-Vela, Sonia; Yeh, Chih-Ching; Austin, John H.M.; Dounel, Matthew; Powell, Charles A.; Reeves, Anthony; Santella, Regina M.; Stevenson, Lori; Yankelevitz, David; Barr, R. Graham

    2009-01-01

    Oxidative stress and inflammation are hallmarks of chronic obstructive pulmonary disease (COPD). A critical byproduct of oxidative damage is the introduction of carbonyl groups into amino acid residues. We hypothesize that plasma carbonyl content is inversely correlated with lung function and computed tomography (CT) measures of lung density among smokers and is elevated in COPD. Carbonyl was measured in plasma of participants aged 60 years and older by ELISA. Generalized linear and additive models were used to adjust for potential confounders. Among 541 participants (52% male, mean age 67 years, 41% current smokers), mean plasma carbonyl content was 17.9±2.9 nmol ml−1 and mean forced expiratory volume in one second (FEV1) was 80.7±20.9% of predicted. Plasma carbonyl content was inversely associated with FEV1, but this relationship was largely explained by age. Multivariate analyses ruled out clinically meaningful associations of plasma carbonyl content with FEV1, FEV1/FVC (forced vital capacity) ratio, severity of airflow obstruction, and CT lung density. Plasma carbonyl content is a poor biomarker of oxidative stress in COPD and emphysema. PMID:18484356

  15. ACCELERATORS: A GUI tool for beta function measurement using MATLAB

    NASA Astrophysics Data System (ADS)

    Chen, Guang-Ling; Tian, Shun-Qiang; Jiang, Bo-Cheng; Liu, Gui-Min

    2009-04-01

    The beta function measurement is used to detect the shift in the betatron tune as the strength of an individual quadrupole magnet is varied. A GUI (graphic user interface) tool for the beta function measurement is developed using the MATLAB program language in the Linux environment, which facilitates the commissioning of the Shanghai Synchrotron Radiation Facility (SSRF) storage ring. In this paper, we describe the design of the application and give some measuring results and discussions about the definition of the measurement. The program has been optimized to solve some restrictions of the AT tracking code. After the correction with LOCO (linear optics from closed orbits), the horizontal and the vertical root mean square values (rms values) can be reduced to 0.12 and 0.10.

  16. What does airway resistance tell us about lung function?

    PubMed

    Kaminsky, David A

    2012-01-01

    Spirometry is considered the primary method to detect the air flow limitation associated with obstructive lung disease. However, air flow limitation is the end-result of many factors that contribute to obstructive lung disease. One of these factors is increased airway resistance. Airway resistance is traditionally measured by relating air flow and driving pressure using body plethysmography, thus deriving airway resistance (R(aw)), specific airway resistance (sR(aw)), and specific airway conductance (sG(aw)). Other methods to measure airway resistance include the forced oscillation technique (FOT), which allows calculation of respiratory system resistance (R(RS)) and reactance (X(RS)), and the interrupter technique, which allows calculation of interrupter resistance (R(int)). An advantage of these other methods is that they may be easier to perform than spirometry, making them particularly suited to patients who cannot perform spirometry, such as young children, patients with neuromuscular disorders, or patients on mechanical ventilation. Since spirometry also requires a deep inhalation, which can alter airway resistance, these alternative methods may provide more sensitive measures of airway resistance. Furthermore, the FOT provides unique information about lung mechanics that is not available from analysis using spirometry, body plethysmography, or the interrupter technique. However, it is unclear whether any of these measures of airway resistance contribute clinically important information to the traditional measures derived from spirometry (FEV(1), FVC, and FEV(1)/FVC). The purpose of this paper is to review the physiology and methodology of these measures of airway resistance, and then focus on their clinical utility in relation to each other and to spirometry.

  17. Impact of the Loss of Hoxa5 Function on Lung Alveogenesis

    PubMed Central

    Mandeville, Isabel; Aubin, Josée; LeBlanc, Michelle; Lalancette-Hébert, Mélanie; Janelle, Marie-France; Tremblay, Guy M.; Jeannotte, Lucie

    2006-01-01

    The involvement of genes controlling embryonic processes in the etiology of diseases often escapes attention because of the focus given to their inherent developmental role. Hoxa5 belongs to the Hox gene family encoding transcription factors known for their role in skeletal patterning. Hoxa5 is required for embryonic respiratory tract morphogenesis. We now show that the loss of Hoxa5 function has severe repercussions on postnatal lung development. Hoxa5−/− lungs present an emphysema-like morphology because of impaired alveogenesis. Chronic inflammation characteristics, including goblet cell hyperplasia, mucus hypersecretion, and recruitment of inflammatory cells, were also observed. Altered cell specification during lung morphogenesis triggered goblet cell anomalies. In addition, the defective motility of alveolar myofibroblast precursors in the embryonic lung led to the mispositioning of the alveolar myofibroblasts and to abnormal elastin deposition postnatally. Both goblet cell hyperplasia and elastic fiber abnormalities contributed to the chronic physiopathological features of Hoxa5−/− lungs. They constituted an attractive stimulus to recruit activated macrophages that in turn generated a positive feedback loop that perpetuated macrophage accumulation in the lung. The present work corroborates the notion that altered Hox gene expression may predispose to lung pathologies. PMID:17003488

  18. Routine Use of Continuous, Hyperfractionated, Accelerated Radiotherapy for Non-Small-Cell Lung Cancer: A Five-Center Experience

    SciTech Connect

    Din, Omar S. Lester, Jason; Cameron, Alison; Ironside, Janet; Gee, Amanda; Falk, Stephen; Morgan, Sally A.; Worvill, Jackie; Hatton, Matthew Q.F.

    2008-11-01

    Purpose: To report the results from continuous, hyperfractionated, accelerated radiotherapy (CHART) used as the standard fractionation for radical RT in the management of non-small cell lung cancer (NSCLC) in five United Kingdom centers. Methods and Materials: In 2005, the CHART consortium identified six U.K. centers that had continued to use CHART after the publication of the CHART study in 1997. All centers had been using CHART for >5 years and agreed to use a common database to audit their results. Patients treated with CHART between 1998 and December 2003 were identified to allow a minimum of 2 years of follow-up. Patient demographics, tumor characteristics, treatment details, and survival were recorded retrospectively. Five centers completed the data collection. Results: A total of 583 patients who had received CHART were identified. Of these patients, 69% were male, with a median age of 68 years (range, 31-89); 83% had performance status 0 or 1; and 43% had Stage I or II disease. Of the 583 patients, 99% received the prescribed dose. In only 4 patients was any Grade 4-5 toxicity documented. The median survival from the start of RT was 16.2 months, and the 2-year survival rate of 34% was comparable to that reported in the original study. Conclusion: The results of this unselected series have confirmed that CHART is deliverable in routine clinical practice, with low levels of toxicity. Importantly, this series has demonstrated that the results of CHART reported from the randomized trial can be reproduced in routine clinical practice.

  19. The effects of in utero vitamin D deficiency on airway smooth muscle mass and lung function.

    PubMed

    Foong, Rachel E; Bosco, Anthony; Jones, Anya C; Gout, Alex; Gorman, Shelley; Hart, Prue H; Zosky, Graeme R

    2015-11-01

    We have previously demonstrated increased airway smooth muscle (ASM) mass and airway hyperresponsiveness in whole-life vitamin D-deficient female mice. In this study, we aimed to uncover the molecular mechanisms contributing to altered lung structure and function. RNA was extracted from lung tissue of whole-life vitamin D-deficient and -replete female mice, and gene expression patterns were profiled by RNA sequencing. The data showed that genes involved in embryonic organ development, pattern formation, branching morphogenesis, Wingless/Int signaling, and inflammation were differentially expressed in vitamin D-deficient mice. Network analysis suggested that differentially expressed genes were connected by the hubs matrix metallopeptidase 9; NF-κ light polypeptide gene enhancer in B cells inhibitor, α; epidermal growth factor receptor; and E1A binding protein p300. Given our findings that developmental pathways may be altered, we investigated if the timing of vitamin D exposure (in utero vs. postnatal) had an impact on lung health outcomes. Gene expression was measured in in utero or postnatal vitamin D-deficient mice, as well as whole-life vitamin D-deficient and -replete mice at 8 weeks of age. Baseline lung function, airway hyperresponsiveness, and airway inflammation were measured and lungs fixed for lung structure assessment using stereological methods and quantification of ASM mass. In utero vitamin D deficiency was sufficient to increase ASM mass and baseline airway resistance and alter lung structure. There were increased neutrophils but decreased lymphocytes in bronchoalveolar lavage. Expression of inflammatory molecules S100A9 and S100A8 was mainly increased in postnatal vitamin D-deficient mice. These observations suggest that in utero vitamin D deficiency can alter lung structure and function and increase inflammation, contributing to symptoms in chronic diseases, such as asthma.

  20. Adolescent lung function associated with incense burning and other environmental exposures at home.

    PubMed

    Chen, Y C; Ho, W C; Yu, Y H

    2016-11-17

    Incense burning is a popular cultural and religious practice, but whether exposure to incense smoke has effects on lung function is unclear. We investigated association between lung function and incense burning exposure and other household exposures in adolescents who participated in a mass asthma-screening program. Information on asthmatic status and associated factors was obtained from parent-completed questionnaires and student-completed video questionnaires. Approximately 10% of students received lung function examinations. Valid lung function data of 5010 students aged 14-16 years in northern Taiwan were analyzed. Forced vital capacity (FVC) and forced expiratory flow in 1 second (FEV1 ) were compared by incense burning status and other types of exposures for adolescents. Overall, 70.6% of students were exposed to incense smoke at home. The mean FVC and FEV1 measures were lower among adolescents with daily exposure to incense burning than those without such exposure (P<.05). Sharing bedroom was also associated with decreased FVC and FEV1 . After controlling for confounding factors, multivariable linear regression analysis with generalized estimation equation showed that FVC was negatively associated with daily exposure to incense burning, sharing a bedroom, and living in a house adjacent to a traffic road. Such associations were also observed in FEV1 . Daily exposure to incense burning is associated with impaired adolescent lung function.

  1. Association between the Type of Workplace and Lung Function in Copper Miners

    PubMed Central

    Gruszczyński, Leszek; Wojakowska, Anna; Ścieszka, Marek; Turczyn, Barbara; Schmidt, Edward

    2016-01-01

    The aim of the analysis was to retrospectively assess changes in lung function in copper miners depending on the type of workplace. In the groups of 225 operators, 188 welders, and 475 representatives of other jobs, spirometry was performed at the start of employment and subsequently after 10, 20, and 25 years of work. Spirometry Longitudinal Data Analysis software was used to estimate changes in group means for FEV1 and FVC. Multiple linear regression analysis was used to assess an association between workplace and lung function. Lung function assessed on the basis of calculation of longitudinal FEV1 (FVC) decline was similar in all studied groups. However, multiple linear regression model used in cross-sectional analysis revealed an association between workplace and lung function. In the group of welders, FEF75 was lower in comparison to operators and other miners as early as after 10 years of work. Simultaneously, in smoking welders, the FEV1/FVC ratio was lower than in nonsmokers (p < 0,05). The interactions between type of workplace and smoking (p < 0,05) in their effect on FVC, FEV1, PEF, and FEF50 were shown. Among underground working copper miners, the group of smoking welders is especially threatened by impairment of lung ventilatory function. PMID:27274987

  2. Oral iodinated activated charcoal improves lung function in patients with COPD.

    PubMed

    Skogvall, Staffan; Erjefält, Jonas S; Olin, Anders I; Ankerst, Jaro; Bjermer, Leif

    2014-06-01

    The effect of 8 weeks treatment with oral iodinated activated charcoal (IAC) on lung function of patients with moderate chronic obstructive pulmonary disease (COPD) was examined in a double blind randomized placebo controlled parallel group study with 40 patients. In the IAC group, patients showed a statistically significant improvement of FEV1 baseline by 130 ml compared to placebo, corresponding to 8.2% improvement (p = 0.031*). Correlation statistics revealed that the improvement of FEV1 baseline was significantly correlated both to FEV1 post-bronchodilator (p = 0.0020**) and FEV1 post-exercise (0.033*) values. This demonstrates that the improved baseline lung function by IAC did not inhibit a further beta2-adrenoceptor relaxation, and thus that patients did not reach a limit for maximal improvement of the lung function after IAC treatment. Eight patients in the IAC group developed abnormal thyroid hormone levels transiently during the treatment. This side effect was not correlated to improvement of lung function (p = 0.82). No serious adverse effects directly related to the treatment were recorded. In summary, this study demonstrates that iodinated activated charcoal surprisingly and significantly improved lung function of patients with moderate COPD. The underlying mechanism of action is unclear, but is likely to be different from the drugs used today. The immediate conclusion is that further studies are now justified in order to determine clinical efficacy of IAC in COPD and explore possible mechanisms of action.

  3. Lung function decline rates according to GOLD group in patients with chronic obstructive pulmonary disease

    PubMed Central

    Kim, Joohae; Yoon, Ho Il; Oh, Yeon-Mok; Lim, Seong Yong; Lee, Ji-Hyun; Kim, Tae-Hyung; Lee, Sang Yeub; Lee, Jin Hwa; Lee, Sang-Do; Lee, Chang-Hoon

    2015-01-01

    Background Since the Global Initiative for Chronic Obstructive Lung Disease (GOLD) groups A–D were introduced, the lung function changes according to group have been evaluated rarely. Objective We investigated the rate of decline in annual lung function in patients categorized according to the 2014 GOLD guidelines. Methods Patients with COPD included in the Korean Obstructive Lung Disease (KOLD) prospective study, who underwent yearly postbronchodilator spirometry at least three times, were included. The main outcome was the annual decline in postbronchodilator forced expiratory volume in 1 second (FEV1), which was analyzed by random-slope and random-intercept mixed linear regression. Results A total 175 participants were included. No significant postbronchodilator FEV1 decline was observed between the groups (−34.4±7.9 [group A]; −26.2±9.4 [group B]; −22.7±16.0 [group C]; and −24.0±8.7 mL/year [group D]) (P=0.79). The group with less symptoms (−32.3±7.2 vs −25.0±6.5 mL/year) (P=0.44) and the low risk group (−31.0±6.1 vs −23.6±7.7 mL/year) (P=0.44) at baseline showed a more rapid decline in the postbronchodilator FEV1, but the trends were not statistically significant. However, GOLD stages classified by FEV1 were significantly related to the annual lung function decline. Conclusion There was no significant difference in lung function decline rates according to the GOLD groups. Prior classification using postbronchodilator FEV1 predicts decline in lung function better than does the new classification. PMID:26379432

  4. Association of perfluoroalkyl substances exposure with impaired lung function in children.

    PubMed

    Qin, Xiao-Di; Qian, Zhengmin Min; Dharmage, Shyamali C; Perret, Jennifer; Geiger, Sarah Dee; Rigdon, Steven E; Howard, Steven; Zeng, Xiao-Wen; Hu, Li-Wen; Yang, Bo-Yi; Zhou, Yang; Li, Meng; Xu, Shu-Li; Bao, Wen-Wen; Zhang, Ya-Zhi; Yuan, Ping; Wang, Jia; Zhang, Chuan; Tian, Yan-Peng; Nian, Min; Xiao, Xiang; Chen, Wen; Lee, Yungling Leo; Dong, Guang-Hui

    2017-02-04

    Previous studies have demonstrated associations between serum levels of perfluoroalkyl substances (PFASs) and asthma or asthma related-biomarkers. However, no studies have reported a possible relationship between PFASs exposure and lung function among children. The objective of the present study is to test the association between PFASs exposure and lung function in children from a high exposure area by using a cross-sectional case-control study, which included 132 asthmatic children and 168 non-asthmatic controls recruited from 2009 to 2010 in the Genetic and Biomarkers study for Childhood Asthma. Structured questionnaires were administered face-to-face. Lung function was measured by spirometry. Linear regression models were used to examine the influence of PFASs on lung function. The results showed that asthmatics in our study had significantly higher serum PFAS concentrations than healthy controls. Logistic regression models showed a positive association between PFASs and asthma, with adjusted odds ratios (ORs) ranging from 0.99 (95% confidence interval [CI]: 0.80-1.21) to 2.76 (95% CI: 1.82-4.17). Linear regression modeling showed serum PFASs levels were significantly negatively associated with three pulmonary function measurements (forced vital capacity: FVC; forced expiratory volume in 1s: FEV1; forced expiratory flow 25-75%: FEF25-75) among children with asthma, the adjusted coefficients between lung function and PFASs exposure ranged from -0.055 (95%CI: -0.100 to -0.010) for FVC and perfluorooctane sulfonate (PFOS) to -0.223 (95%CI: -0.400 to -0.045) for FEF25-75 and perfluorooctanoic acid (PFOA). PFASs were not, however, significantly associated with pulmonary function among children without asthma. In conclusion, this study suggests that serum PFASs are associated with decreased lung function among children with asthma.

  5. X-Ray based Lung Function measurement–a sensitive technique to quantify lung function in allergic airway inflammation mouse models

    PubMed Central

    Dullin, C.; Markus, M. A.; Larsson, E.; Tromba, G.; Hülsmann, S.; Alves, F.

    2016-01-01

    In mice, along with the assessment of eosinophils, lung function measurements, most commonly carried out by plethysmography, are essential to monitor the course of allergic airway inflammation, to examine therapy efficacy and to correlate animal with patient data. To date, plethysmography techniques either use intubation and/or restraining of the mice and are thus invasive, or are limited in their sensitivity. We present a novel unrestrained lung function method based on low-dose planar cinematic x-ray imaging (X-Ray Lung Function, XLF) and demonstrate its performance in monitoring OVA induced experimental allergic airway inflammation in mice and an improved assessment of the efficacy of the common treatment dexamethasone. We further show that XLF is more sensitive than unrestrained whole body plethysmography (UWBP) and that conventional broncho-alveolar lavage and histology provide only limited information of the efficacy of a treatment when compared to XLF. Our results highlight the fact that a multi-parametric imaging approach as delivered by XLF is needed to address the combined cellular, anatomical and functional effects that occur during the course of asthma and in response to therapy. PMID:27805632

  6. X-Ray based Lung Function measurement-a sensitive technique to quantify lung function in allergic airway inflammation mouse models.

    PubMed

    Dullin, C; Markus, M A; Larsson, E; Tromba, G; Hülsmann, S; Alves, F

    2016-11-02

    In mice, along with the assessment of eosinophils, lung function measurements, most commonly carried out by plethysmography, are essential to monitor the course of allergic airway inflammation, to examine therapy efficacy and to correlate animal with patient data. To date, plethysmography techniques either use intubation and/or restraining of the mice and are thus invasive, or are limited in their sensitivity. We present a novel unrestrained lung function method based on low-dose planar cinematic x-ray imaging (X-Ray Lung Function, XLF) and demonstrate its performance in monitoring OVA induced experimental allergic airway inflammation in mice and an improved assessment of the efficacy of the common treatment dexamethasone. We further show that XLF is more sensitive than unrestrained whole body plethysmography (UWBP) and that conventional broncho-alveolar lavage and histology provide only limited information of the efficacy of a treatment when compared to XLF. Our results highlight the fact that a multi-parametric imaging approach as delivered by XLF is needed to address the combined cellular, anatomical and functional effects that occur during the course of asthma and in response to therapy.

  7. X-Ray based Lung Function measurement–a sensitive technique to quantify lung function in allergic airway inflammation mouse models

    NASA Astrophysics Data System (ADS)

    Dullin, C.; Markus, M. A.; Larsson, E.; Tromba, G.; Hülsmann, S.; Alves, F.

    2016-11-01

    In mice, along with the assessment of eosinophils, lung function measurements, most commonly carried out by plethysmography, are essential to monitor the course of allergic airway inflammation, to examine therapy efficacy and to correlate animal with patient data. To date, plethysmography techniques either use intubation and/or restraining of the mice and are thus invasive, or are limited in their sensitivity. We present a novel unrestrained lung function method based on low-dose planar cinematic x-ray imaging (X-Ray Lung Function, XLF) and demonstrate its performance in monitoring OVA induced experimental allergic airway inflammation in mice and an improved assessment of the efficacy of the common treatment dexamethasone. We further show that XLF is more sensitive than unrestrained whole body plethysmography (UWBP) and that conventional broncho-alveolar lavage and histology provide only limited information of the efficacy of a treatment when compared to XLF. Our results highlight the fact that a multi-parametric imaging approach as delivered by XLF is needed to address the combined cellular, anatomical and functional effects that occur during the course of asthma and in response to therapy.

  8. OZONE-INDUCED RESPIRATORY SYMPTOMS AND LUNG FUNCTION DECREMENTS IN HUMANS: EXPOSURE-RESPONSE MODELS

    EPA Science Inventory

    Short duration exposure to ozone (<8 hr) is known to result in lung function decrements and respiratory symptoms in humans. The magnitudes of these responses are functions of ozone concentration (C), activity level measured by minute ventilation (Ve), duration of exposure (T), a...

  9. The potential for resident lung mesenchymal stem cells to promote functional tissue regeneration: understanding microenvironmental cues.

    PubMed

    Foronjy, Robert F; Majka, Susan M

    2012-12-01

    Tissue resident mesenchymal stem cells (MSCs) are important regulators of tissue repair or regeneration, fibrosis, inflammation, angiogenesis and tumor formation. Bone marrow derived mesenchymal stem cells (BM-MSCs) and endothelial progenitor cells (EPC) are currently being considered and tested in clinical trials as a potential therapy in patients with such inflammatory lung diseases including, but not limited to, chronic lung disease, pulmonary arterial hypertension (PAH), pulmonary fibrosis (PF), chronic obstructive pulmonary disease (COPD)/emphysema and asthma. However, our current understanding of tissue resident lung MSCs remains limited. This review addresses how environmental cues impact on the phenotype and function of this endogenous stem cell pool. In addition, it examines how these local factors influence the efficacy of cell-based treatments for lung diseases.

  10. Nasal airway ion transport and lung function in young people with cystic fibrosis.

    PubMed

    Wallace, Helen L; Barker, Pierre M; Southern, Kevin W

    2003-09-01

    There is strong evidence that abnormal airway ion transport is the primary defect that initiates the pathophysiology of lung disease in cystic fibrosis (CF). To examine the relationship between airway ion transport abnormality and severity of lung disease, we measured nasal potential difference in 51 young people with CF using a validated modified technique. There was no correlation between any component of the ion transport measurement and clinical condition (respiratory function, chest radiograph score, or Shwachman clinical score). Thirty subjects, homozygous for the DeltaF508 mutation, were divided into those above and those below average respiratory function for their age. There was no significant difference in any of the ion transport parameters between those with above and below average pulmonary function. Of the 51 subjects, 10 had significant hyperpolarization after perfusion with a zero Cl- solution (> 5 mV). This Cl- secretory capacity did not correlate with above average lung function. These data do not support the assertion that the extent of lung disease in CF reflects the degree of ion transport abnormality. We suggest that although an ion transport abnormality initiates lung disease, other factors (e.g., environmental and genetic modifiers) are more influential in determining disease severity.

  11. Benzo(a)pyrene induced structural and functional modifications in lung cystatin.

    PubMed

    Khan, Mohd Shahnawaz; Priyadarshini, Medha; Shah, Aaliya; Tabrez, Shams; Jagirdar, Haseeb; Alsenaidy, Abdulrahman M; Bano, Bilqees

    2013-10-01

    Cystatins are thiol proteinase inhibitors ubiquitously present in the mammalian body. They serve a protective function to regulate the activities of endogenous proteinases, which may cause uncontrolled proteolysis and damage. In the present study, the effect of benzo(a)pyrene [BaP] on lung cystatin was studied to explore the hazardous effects of environmental pollutant on structural and functional integrity of the protein. The basic binding interaction was studied by UV-absorption, FT-IR, and fluorescence spectroscopy. The enhancement of total protein fluorescence with a red shift of 5 nm suggests structural scratch of lung cystatin by benzo(a)pyrene. Further, ANS binding studies reaffirm the unfolding of the thiol protease inhibitor (GLC-I) after treating with benzo(a)pyrene. The results of FT-IR spectroscopy reflect perturbation of the secondary conformation (alpha-helix to β-sheet) in goat lung cystatin on interaction with BaP. Finally, functional inactivation of cystatin on association with BaP was checked by its papain inhibitory activity. Benzo(a)pyrene (10 μM) caused complete inactivation of goat lung cystatin. Benzo(a)pyrene-induced loss of structure and function in the thiol protease inhibitor could provide a caution for lung injury caused by the pollutants and smokers.

  12. Functional improvement in patients with idiopathic pulmonary fibrosis undergoing single lung transplantation *

    PubMed Central

    Rubin, Adalberto Sperb; Nascimento, Douglas Zaione; Sanchez, Letícia; Watte, Guilherme; Holand, Arthur Rodrigo Ronconi; Fassbind, Derrick Alexandre; Camargo, José Jesus

    2015-01-01

    Abstract Objective: To evaluate the changes in lung function in the first year after single lung transplantation in patients with idiopathic pulmonary fibrosis (IPF). Methods: We retrospectively evaluated patients with IPF who underwent single lung transplantation between January of 2006 and December of 2012, reviewing the changes in the lung function occurring during the first year after the procedure. Results: Of the 218 patients undergoing lung transplantation during the study period, 79 (36.2%) had IPF. Of those 79 patients, 24 (30%) died, and 11 (14%) did not undergo spirometry at the end of the first year. Of the 44 patients included in the study, 29 (66%) were men. The mean age of the patients was 57 years. Before transplantation, mean FVC, FEV1, and FEV1/FVC ratio were 1.78 L (50% of predicted), 1.48 L (52% of predicted), and 83%, respectively. In the first month after transplantation, there was a mean increase of 12% in FVC (400 mL) and FEV1 (350 mL). In the third month after transplantation, there were additional increases, of 5% (170 mL) in FVC and 1% (50 mL) in FEV1. At the end of the first year, the functional improvement persisted, with a mean gain of 19% (620 mL) in FVC and 16% (430 mL) in FEV1. Conclusions: Single lung transplantation in IPF patients who survive for at least one year provides significant and progressive benefits in lung function during the first year. This procedure is an important therapeutic alternative in the management of IPF. PMID:26398749

  13. Assessing lung function and respiratory health in schoolchildren as a means to improve local environmental conditions.

    PubMed

    Hutter, Hans-Peter; Borsoi, Livia; Wallner, Peter; Moshammer, Hanns; Kundi, Michael

    2009-07-01

    In response to the World Health Organization Children's Environment and Health Action Plan for Europe (CEHAPE), a town near Vienna initiated a health survey of schoolchildren. To create recommendations for the community's decision makers, the health survey tried to identify the environmental factors influencing the respiratory health of children. The survey consisted of a questionnaire and spirometry. For 186 of 207 children of first and second grade, parents consented to include their children and answered a questionnaire. Spirometry was performed in 177 children. Results of lung function testing revealed that lung function was significantly reduced in children with visible mould infestation at home and living on a street with frequent lorry traffic. Larger family size and living in a rural area had positive effects on lung function. Our study provides an example for a feasible strategy to provide local decision makers with recommendations based on scientific evidence and actual observations and to help them implement measures in accordance with CEHAPE.

  14. The effects of ambient NO[sub 2] on lung function in primary schoolchildren

    SciTech Connect

    Frischer, T.; Studnicka, M.; Beer, E.; Neumann, M. )

    1993-08-01

    The effect of ambient NO2 on lung function was investigated in a sample of 423 schoolchildren. At each of four locations NO2 was monitored continuously. Over a 6-month period from January to June 1990 two surveys were performed and spirometry recorded each time for each child. Linear regression was used to estimate the effect of NO2 for different time intervals preceding lung function testing. A decrease of NO2 between surveys was significantly associated with a higher forced vital capacity (FVC) at the second survey. For each microgram/m3 NO2 decrease the model predicted an increase in FVC of 1.5 ml [for the 2-hr mean (P < 0.05)] and 3.1 ml [for the 12-hr mean (P < 0.01)]. We conclude that even at NO2 levels below current air-quality standards children demonstrate significant changes in lung function.

  15. Functional and inflammatory alterations in the lung following exposure of rats to nitrogen mustard

    SciTech Connect

    Sunil, Vasanthi R.; Patel, Kinal J.; Shen, Jianliang; Reimer, David; Gow, Andrew J.; Laskin, Jeffrey D.; Laskin, Debra L.

    2011-01-01

    Nitrogen mustard is a vesicant that causes damage to the respiratory tract. In these studies, we characterized the acute effects of nitrogen mustard on lung structure, inflammatory mediator expression, and pulmonary function, with the goal of identifying mediators potentially involved in toxicity. Treatment of rats (male Wistar, 200-225 g) with nitrogen mustard (mechlorethamine hydrochloride, i.t., 0.25 mg/kg) resulted in marked histological changes in the respiratory tract, including necrotizing bronchiolitis, thickening of alveolar septa, and inflammation which was evident within 24 h. This was associated with increases in bronchoalveolar lavage protein and cells, confirming injury to alveolar epithelial regions of the lung. Nitrogen mustard administration also resulted in increased expression of inducible nitric oxide synthase and cyclooxygenase-2, pro-inflammatory proteins implicated in lung injury, in alveolar macrophages and alveolar and bronchial epithelial cells. Expression of connective tissue growth factor and matrix metalloproteinase-9, mediators regulating extracellular matrix turnover was also increased, suggesting that pathways leading to chronic lung disease are initiated early in the pathogenic process. Following nitrogen mustard exposure, alterations in lung mechanics and function were also observed. These included decreases in baseline static compliance, end-tidal volume and airway resistance, and a pronounced loss of methacholine responsiveness in resistance, tissue damping and elastance. Taken together, these data demonstrate that nitrogen mustard induces rapid structural and inflammatory changes in the lung which are associated with altered lung functioning. Understanding the nature of the injury induced by nitrogen mustard and related analogs may aid in the development of efficacious therapies for treatment of pulmonary injury resulting from exposure to vesicants.

  16. [Acute effect of ambient air pollution on small airway lung functions among school children in Shanghai].

    PubMed

    Zhang, L J; Guo, C Y; Xu, H H; Xu, D; Shen, X B; Du, X Y; Zhang, M H; Tan, J G; Zhang, J H; Dong, C Y; Qian, H L; Shi, Y W; Pan, M Z; Zhou, X D

    2017-02-10

    Objective: To study the acute effects of compound ambient air pollution on small airway lung functions among school children in Shanghai. Method: A longitudinal survey on lung functions was conducted among 233 school-children from three schools (A, B and C, located in innerring, mid-ring and outer-ring areas). Lung function test was performed once a week for 3 times respectively, among children in school A and B in Dec. 2013 and in school C in Dec. 2014. The fourth lung function test was tested in Jun. 2014 and May 2015 in the respective schools. Results: from the lung function would include items as: forced mid-expiratory flow at 25% of forced vital capacity (MEF(25%)), mid-expiratory flow at 50% of forced vital capacity (MEF(50%)), mid-expiratory flow at 75% of forced vital capacity (MEF(75%)) and mid-expiratory flow between 25% and 75% of the forced vital capacity (FEF(25%-75%)). Data regarding the daily air quality real-time of PM(2.5), PM(10), SO(2) and NO(2) in Dec. 2013, Dec. 2014, Jun. 2014 and May. 2015 from the three environmental monitoring spots and meteorological data from the Shanghai Meteorological Service system which were physically close to the three schools, were collected simultaneously. Linear mixed effect model was used to examine the levels of correlation between lung function indicators and ambient air pollutants. Results When confounding factors on meteorology and individuals were controlled, the lag effects and accumulated lag effects were found to have existed between the internal quarter rang (IQR) concentration of PM(2.5) and PM(10) in lag2 day and lag02 days, IQR concentration of SO(2) in lag02 day and IQR concentration of NO(2) lag0 day, when small airway lung functions like MEF(25%), MEF(50%), MEF(75%) and FEF(25%-75%)(P<0.05) were inspected. Results from the two air pollutants model analysis showed that SO(2) and NO(2) presenting interactive effects with PM(2.5), PM(10) and lag effects more significant than the individual SO(2) and

  17. Psychological functioning of pediatric lung transplant candidates/recipients: a review of the literature.

    PubMed

    Brosig, Cheryl L

    2003-10-01

    Although lung transplants are performed in children, experience with the pediatric population remains limited. There is growing interest in studying the psychological functioning and quality of life in these patients following transplant. There is a body of literature about quality of life in adult lung transplant recipients, but little is known about how pediatric patients and their families function psychologically after transplant. The current article summarizes the pediatric literature with respect to psychological outcomes for transplant recipients and their parents and points to areas where additional research is needed.

  18. Pharmacological characterization of the late phase reduction in lung functions and correlations with microvascular leakage and lung edema in allergen-challenged Brown Norway rats.

    PubMed

    Mauser, Peter J; House, Aileen; Jones, Howard; Correll, Craig; Boyce, Christopher; Chapman, Richard W

    2013-12-01

    Late phase airflow obstruction and reduction in forced vital capacity are characteristic features of human asthma. Airway microvascular leakage and lung edema are also present in the inflammatory phase of asthma, but the impact of this vascular response on lung functions has not been precisely defined. This study was designed to evaluate the role of increased lung microvascular leakage and edema on the late phase changes in forced vital capacity (FVC) and peak expiratory flow (PEF) in allergen-challenged Brown Norway rats using pharmacological inhibitors of the allergic inflammatory response. Rats were sensitized and challenged with ovalbumin aerosol and forced expiratory lung functions (FVC, PEF) and wet and dry lung weights were measured 48 h after antigen challenge. Ovalbumin challenge reduced FVC (63% reduction) and PEF (33% reduction) and increased wet (65% increase) and dry (51% increase) lung weights. The antigen-induced reduction in FVC and PEF was completely inhibited by oral treatment with betamethasone and partially attenuated by inhibitors of arachidonic acid metabolism including indomethacin (cyclooxygenase inhibitor), 7-TM and MK-7246 (CRTH2 antagonists) and montelukast (CysLT1 receptor antagonist). Antagonists of histamine H1 receptors (mepyramine) and 5-HT receptors (methysergide) had no significant effects indicating that these pre-formed mast cell mediators were not involved. There was a highly significant (P < 0.005) correlation for the inhibition of FVC reduction and increase in wet and dry lung weights by these pharmacological agents. These results strongly support the hypothesis that lung microvascular leakage and the associated lung edema contribute to the reduction in forced expiratory lung functions in antigen-challenged Brown Norway rats and identify an important role for the cyclooxygenase and lipoxygenase products of arachidonic acid metabolism in these responses.

  19. Restrictive lung function and asbestos-induced pleural fibrosis. A quantitative approach.

    PubMed Central

    Schwartz, D A; Galvin, J R; Yagla, S J; Speakman, S B; Merchant, J A; Hunninghake, G W

    1993-01-01

    To assess further the clinical significance of asbestos-induced pleural fibrosis, we used a computer algorithm to reconstruct images three dimensionally from the high-resolution computerized tomography (HRCT) scan of the chest in 60 asbestos-exposed subjects. Pulmonary function tests, chest radiographs, and HRCT scans were performed on all study subjects. The volume of asbestos-induced pleural fibrosis was computed from the three-dimensional reconstruction of the HRCT scan. Among those with pleural fibrosis identified on the HRCT scan (n = 29), the volume of the pleural lesion varied from 0.01% (0.5 ml) and 7.11% (260.4 ml) of the total chest cavity. To investigate the relationship between asbestos-induced pleural fibrosis and restrictive lung function, we compared the computer-derived estimate of pleural fibrosis to the total lung capacity and found that these measures were inversely related (r = -0.40; P = 0.002). After controlling for age, height, pack-years of cigarette smoking, and the presence of interstitial fibrosis on the chest radiograph, the volume of pleural fibrosis identified on the three-dimensional reconstructed image from the HRCT scan was inversely associated with the total lung capacity (P = 0.03) and independently accounted for 9.5% of the variance of this measure of lung volume. These findings further extend the scientific data supporting an independent association between pleural fibrosis and restrictive lung function. Images PMID:8514875

  20. Lung Cancer Classification Employing Proposed Real Coded Genetic Algorithm Based Radial Basis Function Neural Network Classifier

    PubMed Central

    Deepa, S. N.

    2016-01-01

    A proposed real coded genetic algorithm based radial basis function neural network classifier is employed to perform effective classification of healthy and cancer affected lung images. Real Coded Genetic Algorithm (RCGA) is proposed to overcome the Hamming Cliff problem encountered with the Binary Coded Genetic Algorithm (BCGA). Radial Basis Function Neural Network (RBFNN) classifier is chosen as a classifier model because of its Gaussian Kernel function and its effective learning process to avoid local and global minima problem and enable faster convergence. This paper specifically focused on tuning the weights and bias of RBFNN classifier employing the proposed RCGA. The operators used in RCGA enable the algorithm flow to compute weights and bias value so that minimum Mean Square Error (MSE) is obtained. With both the lung healthy and cancer images from Lung Image Database Consortium (LIDC) database and Real time database, it is noted that the proposed RCGA based RBFNN classifier has performed effective classification of the healthy lung tissues and that of the cancer affected lung nodules. The classification accuracy computed using the proposed approach is noted to be higher in comparison with that of the classifiers proposed earlier in the literatures. PMID:28050198

  1. Determinants of restrictive lung function in asbestos-induced pleural fibrosis

    SciTech Connect

    Schwartz, D.A.; Galvin, J.R.; Dayton, C.S.; Stanford, W.; Merchant, J.A.; Hunninghake, G.W. )

    1990-05-01

    We evaluated whether restrictive lung function among asbestos-exposed individuals with pleural fibrosis was caused by radiographically inapparent parenchymal inflammation and/or parenchymal fibrosis. All 24 study participants were sheet metal workers who were nonsmokers with normal parenchyma on posteroanterior chest radiograph. These subjects had either normal pleura (n = 7), circumscribed plaques (n = 9), or diffuse pleural thickening (n = 8). After controlling for age, years in the trade, and pack-years of smoking, we found that sheet metal workers with diffuse pleural thickening had a lower forced vital capacity (P less than 0.001), total lung capacity (P less than 0.01), and CO-diffusing capacity of the lung (P less than 0.05) than those with normal pleura. Similarly, sheet metal workers with circumscribed plaques were found to have a reduced forced vital capacity; however, because of the small number of study subjects, this difference (regression coefficient = -11.0) was only marginally significant (P = 0.06). Although circumscribed plaque and diffuse pleural thickening were both associated with a lymphocytic alveolitis and a higher prevalence of parenchymal fibrosis on high-resolution computerized tomography (HRCT) scan, neither a lymphocytic alveolitis nor the finding of parenchymal fibrosis on HRCT scan influenced the relationship between pleural fibrosis and restrictive lung function. We conclude that pleural fibrosis is associated with restrictive lung function and abnormally low diffusion that appears to be independent of our measures of parenchymal injury (chest X-ray, bronchoalveolar lavage, and HRCT scan).

  2. [Assessment of respiratory function in the qualification for lung cancer surgery].

    PubMed

    Franczuk, Monika; Wesołowski, Stefan

    2015-01-01

    Surgery is the treatment of choice in patients with a diagnosis of non-small cell lung cancer (NSCLC). A pivotal of eligibility for resection is the early stage of the disease and histopathological assessment. The performance status and comorbidities in population, predominated by elderly patients, also influence the therapeutic decisions. In some lung cancer patients COPD coexists, characterized by a decrease in lung function. Then the preoperative evaluation is particularly important, for both the risk of postoperative complications, lung function and quality of life postoperatively. Recently several recommendations for preoperative evaluation of patients being considered for surgery were published. The guidelines of BTS (2001, 2010), ACCP (2007, 2013) and joint recommendations of ERS and ESTS (2009) have been based on the currently available research results, and indicated the algorithms. The recommendations ERS/ESTS and ACCP distinguished cardiac risk estimation in all patients, which should precede the evaluation of lung function. According to the latest recommendations (ACCP 2013) the next step is spirometry, DLCO measurement and calculation of predicted postoperative values for both parameters. The low-technology exercise tests (stair climbing, shuttle walk test) were assigned as valuable to discriminate patients at low and intermediate perioperative risk. The cardiopulmonary exercise test (CPET) is recommended to be performed at the final qualification for surgery in patients with high risk. It was also stressed that therapeutic decisions should be taken multidisciplinary, allowing to estimate the risk of complications and to evaluate the expected quality of life in the postoperative time.

  3. Lung Cancer Classification Employing Proposed Real Coded Genetic Algorithm Based Radial Basis Function Neural Network Classifier.

    PubMed

    Selvakumari Jeya, I Jasmine; Deepa, S N

    2016-01-01

    A proposed real coded genetic algorithm based radial basis function neural network classifier is employed to perform effective classification of healthy and cancer affected lung images. Real Coded Genetic Algorithm (RCGA) is proposed to overcome the Hamming Cliff problem encountered with the Binary Coded Genetic Algorithm (BCGA). Radial Basis Function Neural Network (RBFNN) classifier is chosen as a classifier model because of its Gaussian Kernel function and its effective learning process to avoid local and global minima problem and enable faster convergence. This paper specifically focused on tuning the weights and bias of RBFNN classifier employing the proposed RCGA. The operators used in RCGA enable the algorithm flow to compute weights and bias value so that minimum Mean Square Error (MSE) is obtained. With both the lung healthy and cancer images from Lung Image Database Consortium (LIDC) database and Real time database, it is noted that the proposed RCGA based RBFNN classifier has performed effective classification of the healthy lung tissues and that of the cancer affected lung nodules. The classification accuracy computed using the proposed approach is noted to be higher in comparison with that of the classifiers proposed earlier in the literatures.

  4. Diffusive Particle Acceleration in Shocked, Viscous Accretion Disks: Green's Function Energy Distribution

    NASA Astrophysics Data System (ADS)

    Becker, Peter A.; Das, Santabrata; Le, Truong

    2011-12-01

    The acceleration of relativistic particles in a viscous accretion disk containing a standing shock is investigated as a possible explanation for the energetic outflows observed around radio-loud black holes. The energy/space distribution of the accelerated particles is computed by solving a transport equation that includes the effects of first-order Fermi acceleration, bulk advection, spatial diffusion, and particle escape. The velocity profile of the accreting gas is described using a model for shocked viscous disks recently developed by the authors, and the corresponding Green's function distribution for the accelerated particles in the disk and the outflow is obtained using a classical method based on eigenfunction analysis. The accretion-driven, diffusive shock acceleration scenario explored here is conceptually similar to the standard model for the acceleration of cosmic rays at supernova-driven shocks. However, in the disk application, the distribution of the accelerated particles is much harder than would be expected for a plane-parallel shock with the same compression ratio. Hence the disk environment plays a key role in enhancing the efficiency of the shock acceleration process. The presence of the shock helps to stabilize the disk by reducing the Bernoulli parameter, while channeling the excess binding energy into the escaping relativistic particles. In applications to M87 and Sgr A*, we find that the kinetic power in the jet is {\\sim}0.01\\,\\dot{M} c^2, and the outflowing relativistic particles have a mean energy ~300 times larger than that of the thermal gas in the disk at the shock radius. Our results suggest that a standing shock may be an essential ingredient in accretion onto underfed black holes, helping to resolve the long-standing problem of the stability of advection-dominated accretion disks.

  5. Lung function status of workers exposed to wood dust in timber markets in Calabar, Nigeria.

    PubMed

    Okwari, O O; Antai, A B; Owu, D U; Peters, E J; Osim, E E

    2005-06-01

    The effect of chronic exposure to dust from local woods such as ebony, achi, and iroko on lung function of timber market workers in Calabar - Nigeria, was studied. Forced vital capacity (FVC), Forced Expiratory Volume in one second, (FEV1), Forced Expiratory Volume as a percentage of forced vital capacity (FEV1 %), and Peak Expiratory Flow Rate (PEFR) were measured in 221 workers (aged 20-25 years) exposed to wood dust to assess their lung function and compared with 200 age- and sex- matched control subjects who were not exposed to any known air pollutant. The concentration of respirable dust was significantly higher in the test (P<0.001) than in control site. The mean values of FVC, FEV1, FEV1% and PEFR of the timber workers were significantly lower (P<0.01) than in control subjects. Respiratory symptoms such as cough, chest pain and nasal irritation had higher prevalence in the test group than in the control group. Non-respiratory symptoms (skin and eye irritation) were prevalent in the test group but not found in the control group. Workers exposed to wood dust had restrictive pattern of ventilatory function impairment. The lung function indices of the timber workers decreased with their length of service. Chronic exposure to wood dust impairs lung function.

  6. Acute ozone-induced lung injury in rats: Structural-functional relationships of developing alveolar edema

    SciTech Connect

    Paterson, J.F.; Hammond, M.D.; Montgomery, M.R.; Sharp, J.T.; Farrier, S.E.; Balis, J.U. )

    1992-11-01

    As part of a study on the effects of acute ozone stress on the lung surfactant system, we correlated morphometric, biochemical, and functional indices of lung injury using male rats exposed to 3 ppm ozone for 1, 2, 4, and 8 hr. Evaluation of lung mechanics, using the Pulmonary Evaluation and Diagnostic Laboratory System, revealed a significant decrease in dynamic lung compliance (ml/cmH[sub 2]O/kg) from a control value of 0.84 [plus minus] 0.02 (SEM) to 0.72 [plus minus] 0.04 and 0.57 [plus minus] 0.06 at 4 and 8 hr, respectively. At 2 hr there was a transient increase in PaO[sub 2] to 116 torr (control = 92 torr) followed by a decrease at 4 hr (65 torr) and 8 hr (55 torr). Morphometry of lung tissue, fixed by perfusion of fixative via the pulmonary artery at 12 cm H[sub 2]O airway distending pressure, demonstrated an increase in the area of the intravascular compartment at 8 hr, in association with a 65 and 39% replacement of the alveolar area by fluid in ventral and dorsal lung regions, respectively. There was a positive correlation (r = 0.966) between alveolar edema and transudated proteins in lavage fluid. A stepwise multiple regression model, with edema as the dependent variable, suggested that pulmonary vasodilatation, hypoxemia, and depletion of surfactant tubular myelin in lavage fluid were indices for predicting alveolar edema. In a second model, with lavage protein concentration as the dependent variable, decreasing dynamic compliance and hypoxemia were predictors of progressive, intraalveolar transudation of plasma proteins. The above structural-functional relationships support the concept that ozone-induced high-protein alveolar edema is pathogenetically linked to pulmonary hyperemia, deficiency of surfactant tubular myelin, and associated lung dysfunctions.

  7. Enhanced heme function and mitochondrial respiration promote the progression of lung cancer cells.

    PubMed

    Hooda, Jagmohan; Cadinu, Daniela; Alam, Md Maksudul; Shah, Ajit; Cao, Thai M; Sullivan, Laura A; Brekken, Rolf; Zhang, Li

    2013-01-01

    Lung cancer is the leading cause of cancer-related mortality, and about 85% of the cases are non-small-cell lung cancer (NSCLC). Importantly, recent advance in cancer research suggests that altering cancer cell bioenergetics can provide an effective way to target such advanced cancer cells that have acquired mutations in multiple cellular regulators. This study aims to identify bioenergetic alterations in lung cancer cells by directly measuring and comparing key metabolic activities in a pair of cell lines representing normal and NSCLC cells developed from the same patient. We found that the rates of oxygen consumption and heme biosynthesis were intensified in NSCLC cells. Additionally, the NSCLC cells exhibited substantially increased levels in an array of proteins promoting heme synthesis, uptake and function. These proteins include the rate-limiting heme biosynthetic enzyme ALAS, transporter proteins HRG1 and HCP1 that are involved in heme uptake, and various types of oxygen-utilizing hemoproteins such as cytoglobin and cytochromes. Several types of human tumor xenografts also displayed increased levels of such proteins. Furthermore, we found that lowering heme biosynthesis and uptake, like lowering mitochondrial respiration, effectively reduced oxygen consumption, cancer cell proliferation, migration and colony formation. In contrast, lowering heme degradation does not have an effect on lung cancer cells. These results show that increased heme flux and function are a key feature of NSCLC cells. Further, increased generation and supply of heme and oxygen-utilizing hemoproteins in cancer cells will lead to intensified oxygen consumption and cellular energy production by mitochondrial respiration, which would fuel cancer cell proliferation and progression. The results show that inhibiting heme and respiratory function can effectively arrest the progression of lung cancer cells. Hence, understanding heme function can positively impact on research in lung cancer

  8. Nuclear Factor-Kappa-B Signaling in Lung Development and Disease: One Pathway, Numerous Functions

    PubMed Central

    Alvira, Cristina M

    2014-01-01

    In contrast to other organs, the lung completes a significant portion of its development after term birth. During this stage of alveolarization, division of the alveolar ducts into alveolar sacs by secondary septation, and expansion of the pulmonary vasculature by means of angiogenesis markedly increase the gas exchange surface area of the lung. However, postnatal completion of growth renders the lung highly susceptible to environmental insults such as inflammation that disrupt this developmental program. This is particularly evident in the setting of preterm birth, where impairment of alveolarization causes bronchopulmonary dysplasia, a chronic lung disease associated with significant morbidity. The nuclear factor κ-B (NFκB) family of transcription factors are ubiquitously expressed, and function to regulate diverse cellular processes including proliferation, survival, and immunity. Extensive evidence suggests that activation of NFκB is important in the regulation of inflammation and in the control of angiogenesis. Therefore, NFκB-mediated downstream effects likely influence the lung response to injury and may also mediate normal alveolar development. This review summarizes the main biologic functions of NFκB, and highlights the regulatory mechanisms that allow for diversity and specificity in downstream gene activation. This is followed by a description of the pro and anti-inflammatory functions of NFκB in the lung, and of NFκB-mediated angiogenic effects. Finally, this review summarizes the clinical and experimental data that support a role for NFκB in mediating postnatal angiogenesis and alveolarization, and discusses the challenges that remain in developing therapies that can selectively block the detrimental functions of NFκB yet preserve the beneficial effects. Birth Defects Research (Part A) 100:202–216, 2014. © 2014 Wiley Periodicals, Inc. PMID:24639404

  9. Relationship of lung function loss to level of initial function: correcting for measurement error using the reliability coefficient.

    PubMed Central

    Irwig, L; Groeneveld, H; Becklake, M

    1988-01-01

    The regression of lung function change on the initial lung function level is biased when the initial level is measured with random error. Several methods have been proposed to obtain unbiased estimates of regression coefficients in such circumstances. We apply these methods to examine the relationship between lung function loss over 11 years and its initial level in 433 men aged about 20 when first seen. On theoretical and practical grounds the best method is the correction of the regression coefficient using the reliability coefficient. This is defined as the ratio of the error free variance to the variance of the variable measured with error, and is easily estimated as the correlation between repeat measurements of the underlying level. In young men the loss of some lung functions (forced vital capacity [FVC], forced expiratory volume in one second [FEV1], forced expiratory flow in the middle half of expiration, and the ratio FEV1/FVC) do not appear to be related to initial level. PMID:3256581

  10. Shortening tobacco life cycle accelerates functional gene identification in genomic research.

    PubMed

    Ning, G; Xiao, X; Lv, H; Li, X; Zuo, Y; Bao, M

    2012-11-01

    Definitive allocation of function requires the introduction of genetic mutations and analysis of their phenotypic consequences. Novel, rapid and convenient techniques or materials are very important and useful to accelerate gene identification in functional genomics research. Here, over-expression of PmFT (Prunus mume), a novel FT orthologue, and PtFT (Populus tremula) lead to shortening of the tobacco life cycle. A series of novel short life cycle stable tobacco lines (30-50 days) were developed through repeated self-crossing selection breeding. Based on the second transformation via a gusA reporter gene, the promoter from BpFULL1 in silver birch (Betula pendula) and the gene (CPC) from Arabidopsis thaliana were effectively tested using short life cycle tobacco lines. Comparative analysis among wild type, short life cycle tobacco and Arabidopsis transformation system verified that it is optional to accelerate functional gene studies by shortening host plant material life cycle, at least in these short life cycle tobacco lines. The results verified that the novel short life cycle transgenic tobacco lines not only combine the advantages of economic nursery requirements and a simple transformation system, but also provide a robust, effective and stable host system to accelerate gene analysis. Thus, shortening tobacco life cycle strategy is feasible to accelerate heterologous or homologous functional gene identification in genomic research.

  11. Students' Perceptions of Long-Functioning Cooperative Teams in Accelerated Adult Degree Programs

    ERIC Educational Resources Information Center

    Favor, Judy

    2012-01-01

    This study examined 718 adult students' perceptions of long-functioning cooperative study teams in accelerated associate's, bachelor's, and master's business degree programs. Six factors were examined: attraction toward team, alignment of performance expectations, intrateam conflict, workload sharing, preference for teamwork, and impact on…

  12. Long-Term Effects of Traffic Particles on Lung Function Decline in the Elderly

    PubMed Central

    Litonjua, Augusto A.; Coull, Brent; Koutrakis, Petros; Sparrow, David; Vokonas, Pantel S.; Schwartz, Joel

    2014-01-01

    Rationale: Few studies have been performed on air pollution effects on lung function in the elderly, a vulnerable population with low reserve capacity, and even fewer have looked at changes in the rate of lung function decline. Objectives: We evaluated the effect of long-term exposure to black carbon on levels and rates of decline in lung function in the elderly. Methods: FVC and FEV1 were measured one to six times during the period 1995–2011 in 858 men participating in the Normative Aging Study. Exposure to black carbon, a tracer of traffic emissions, was estimated by a spatiotemporal land use regression model. We investigated the effects of moving averages of black carbon of 1–5 years before the lung function measurement using linear mixed models. Measurements and Main Results: A 0.5 μg/m3 increase in long-term exposure to black carbon was associated with an additional rate of decline in FVC and FEV1 of between 0.5% and 0.9% per year, respectively, depending on the averaging time. In addition, black carbon exposure before the baseline visit was associated with lower levels of both FVC and FEV1, with effect estimates increasing up to 6–7% with a 5-year average exposure. Conclusions: Our results support adverse effects of long-term exposure to traffic particles on lung function level and rate of decline in the elderly and suggest that functionally significant differences in health and risk of disability occur below the annual Environmental Protection Agency National Air Quality Standards. PMID:25028775

  13. Effects of indoor air pollution on lung function of primary school children in Kuala Lumpur

    SciTech Connect

    Azizi, B.H.; Henry, R.L. )

    1990-01-01

    In a cross-sectional study of 7-12 year-old primary school children in Kuala Lumpur city, lung function was assessed by spirometric and peak expiratory flow measurements. Spirometric and peak expiratory flow measurements were successfully performed in 1,214 and 1,414 children, respectively. As expected, the main predictors of forced vital capacity (FVC), forced expiratory volume in one second (FEV1), forced expiratory flow between 25% and 75% of vital capacity (FEF25-75), and peak expiratory flow rate (PEFR) were standing height, weight, age, and sex. In addition, lung function values of Chinese and Malays were generally higher than those of Indians. In multiple regression models which included host and environmental factors, asthma was associated with significant decreases in FEV1, FEF25-75, and PEFR. However, family history of chest illness, history of allergies, low paternal education, and hospitalization during the neonatal period were not independent predictors of lung function. Children sharing rooms with adult smokers had significantly lower levels of FEF25-75. Exposures to wood or kerosene stoves were, but to mosquito repellents were not, associated with decreased lung function.

  14. Best lung function equations for the very elderly selected by survival analysis.

    PubMed

    Miller, Martin R; Thinggaard, Mikael; Christensen, Kaare; Pedersen, Ole F; Sigsgaard, Torben

    2014-05-01

    We evaluated which equations best predicted the lung function of a cohort of nonagenarians based on which best accounted for subsequent survival. In 1998, we measured lung function, grip strength and dementia score (Mini Mental State Examination (MMSE)) in a population-based sample of 2262 Danes born in 1905. Mortality was registered to 2011 when only five (0.2%) subjects were alive. In half the cohort, we recorded forced expiratory volume in 1 s (FEV1). Complete data were available in 592 subjects with results expressed as standardised residuals (SR) using various prediction equations. Cox proportional hazard regression found lower FEV1SR was a predictor of mortality having controlled for MMSE, grip strength and sex. The US National Health and Nutrition Examination Survey (NHANES) III (1999) equations gave a better spread of median survival by FEV1SR quartile: 3.94, 3.65, 3.51 and 2.61 years with a hazard ratio for death of 1, 1.16, 1.32 and 1.60 respectively, compared with equations derived with the inclusion of elderly subjects. We conclude that extrapolating from NHANES III equations to predict lung function in nonagenarians gave better survival predictions from spirometry than when employing equations derived using very elderly subjects with possible selection bias. These findings can help inform how future lung function equations for the elderly are derived.

  15. Relationship between birth weight and adult lung function: controlling for maternal factors

    PubMed Central

    Edwards, C; Osman, L; Godden, D; Campbell, D; Douglas, J

    2003-01-01

    Methods: In 2001 the cohort was assessed for current lung function, smoking status, and respiratory symptoms. Birth details obtained from the Aberdeen Maternity and Neonatal Databank recorded birth weight, gestation, parity, and mother's age and height. Results: 381 subjects aged 45–50 years were traced and tested for lung function; 323 (85%) had birth details available. A significant linear trend (p<0.01) was observed between birth weight and current forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) values (adjusted for height, age, sex, weight, deprivation category (Depcat), childhood group, and smoking status). This trend remained significant after adjusting birth weight for gestation, parity, sex, mother's height and weight (p = 0.01). The relationship between birth weight and FEV1 and FVC remained significant when adjusted for smoking history. There was no association between birth weight and current wheezing symptoms. Conclusion: There is a positive linear trend between birth weight, adjusted for maternal factors, and lung function in adulthood. The strength of this association supports the "fetal origins hypothesis" that impairment of fetal growth is a significant influence on adult lung function. PMID:14645976

  16. Effects of combinations of diesel exhaust and ozone exposure on lung function in human volunteers.

    EPA Science Inventory

    Ozone (03) exposure induces changes in human lung function, typically seen as a decrease in forced expiratory volume in one sec (FEV1) and forced vital capacity (FVC). Because people are usually exposed to other ambient air pollutants simultaneously with 03, there may be interact...

  17. Effects of indoor air pollution on lung function of primary school children in Kuala Lumpur.

    PubMed

    Azizi, B H; Henry, R L

    1990-01-01

    In a cross-sectional study of 7-12 year-old primary school children in Kuala Lumpur city, lung function was assessed by spirometric and peak expiratory flow measurements. Spirometric and peak expiratory flow measurements were successfully performed in 1,214 and 1,414 children, respectively. As expected, the main predictors of forced vital capacity (FVC), forced expiratory volume in one second (FEV1), forced expiratory flow between 25% and 75% of vital capacity (FEF25-75), and peak expiratory flow rate (PEFR) were standing height, weight, age, and sex. In addition, lung function values of Chinese and Malays were generally higher than those of Indians. In multiple regression models which included host and environmental factors, asthma was associated with significant decreases in FEV1, FEF25-75, and PEFR. However, family history of chest illness, history of allergies, low paternal education, and hospitalization during the neonatal period were not independent predictors of lung function. Children sharing rooms with adult smokers had significantly lower levels of FEF25-75. Exposures to wood or kerosene stoves were, but to mosquito repellents were not, associated with decreased lung function.

  18. Air pollution, airway inflammation and lung function in Mexico City school children

    EPA Science Inventory

    BACKGROUND: The biological mechanisms involved in inflammatory response to air pollution are not clearly understood. OBJECTIVE: In this study we assessed the association of short-term air pollutant exposure with inflammatory markers and lung function. METHODS: We studied a cohort...

  19. Supine changes in lung function correlate with chronic respiratory failure in myotonic dystrophy patients.

    PubMed

    Poussel, Mathias; Kaminsky, Pierre; Renaud, Pierre; Laroppe, Julien; Pruna, Lelia; Chenuel, Bruno

    2014-03-01

    Quality of life and prognosis of patients with myotonic dystrophy type 1 (MD1) often depend on the degree of lung function impairment. This study was designed to assess the respective prevalence of ventilatory restriction, hypoxaemia and hypercapnia in MD1 patients and to determine whether postural changes in lung function could contribute to the early diagnosis of poor respiratory outcome. Fifty-eight patients (42.6±12.9 years) with MD1 were prospectively evaluated from April 2008 to June 2010 to determine their supine and upright lung function and arterial blood gases. The prevalence of ventilatory restriction was 36% and increased with the severity of muscular disability (from 7.7% to 70.6%). The prevalence of hypoxaemia and hypercapnia was 37.9% and 25.9%, respectively. Multiple regression analysis showed that the supine fall in FEV1 was the only variable associated with ventilatory restriction, hypoxaemia and hypercapnia. Our data indicate that supine evaluation of lung function could be helpful to predict poor respiratory outcome, which is closely correlated with hypoxaemia and/or hypercapnia.

  20. Lung function, respiratory symptoms and venous thromboembolism risk: the Atherosclerosis Risk in Communities Study.

    PubMed

    Kubota, Y; London, S J; Cushman, M; Chamberlain, A M; Rosamond, W D; Heckbert, S R; Zakai, N; Folsom, A R

    2016-12-01

    Essentials The association of lung function with venous thromboembolism (VTE) is unclear. Chronic obstructive pulmonary disease (COPD) patterns were associated with a higher risk of VTE. Symptoms were also associated with a higher risk of VTE, but a restrictive pattern was not. COPD may increase the risk of VTE and respiratory symptoms may be a novel risk marker for VTE.

  1. ENVIRONMENTAL EXPOSURES, LUNG FUNCTION, AND RESPIRATORY HEALTH IN RURAL LAO PDR

    PubMed Central

    Lopez, Jaime R; Somsamouth, Khamphithoune; Mounivong, Boualoy; Sinclair, Ryan; Soret, Sam; Knutsen, Synnove; Singh, Pramil N

    2014-01-01

    Although the individual contributions of smoked tobacco and indoor air pollution have been identified, there are very few studies that have characterized and measured the effects of inhaled particles from a wide range of personal, household, and community practices common in rural Asia. The objective of our study was to examine the association between environmental inhaled exposures and lung function among rural males of Lao PDR. In a sample of 92 males from rural Lao PDR, study subjects completed a survey on household exposures, a physical exam, and the following measures of lung function: FEV1, FVC, and the ratio of FEV1/FVC. Our findings were as follows: a) > 80% of the subjects were exposed to indoor cooking fires (wood fuel), animal handling, dust and dirt; b) 57.6% of subjects were in the impaired range (FEV1/FVC < 0.7); and c) animal handling was negatively associated (p<0.03) with FEV1 and FVC. Among males in rural Lao PDR, we found a high prevalence of chronic exposure to inhaled particles (animal handling, dust/dirt, smoke) and a high prevalence of impaired lung function. Findings from this pilot study indicate that associations between exposure to multiple sources of particulate matter common in rural areas and lung function need further investigation. PMID:24964671

  2. Abnormal ventilation scans in middle-aged smokers. Comparison with tests of overall lung function

    SciTech Connect

    Barter, S.J.; Cunningham, D.A.; Lavender, J.P.; Gibellino, F.; Connellan, S.J.; Pride, N.B.

    1985-07-01

    The uniformity of regional ventilation during tidal breathing has been assessed using continuous inhalation of krypton-81m in 43 male, lifelong nonsmokers and 46 male, current cigarette smokers (mean daily consumption 24.1 cigarettes/day) between 44 and 61 yr of age and with mild or no respiratory symptoms. All subjects had normal chest radiographs. The results of the ventilation scans were compared with tests of overall lung function (spirometry, maximal expiratory flow-volume curves, and single-breath N2 test). Diffuse abnormalities of the ventilation scan were found in 19 (41%) of the 46 smokers but in none of the nonsmokers. Focal abnormalities were found in 7 smokers and 3 nonsmokers. Smokers showed the expected abnormalities in overall lung function (reduced FEV1 and VC, increased single-breath N2 slope, and closing volume), but in individual smokers there was only a weak relation between the severity of abnormality of overall lung function and an abnormal ventilation scan. Abnormal scans could be found when overall lung function was normal and were not invariably found when significant abnormalities in FEV1/VC or N2 slope were present. There was no relation between the presence of chronic expectoration and an abnormal scan. The prognostic significance of an abnormal ventilation scan in such smokers remains to be established.

  3. Lung function in post-poliomyelitis syndrome: a cross-sectional study*

    PubMed Central

    de Lira, Claudio Andre Barbosa; Minozzo, Fábio Carderelli; Sousa, Bolivar Saldanha; Vancini, Rodrigo Luiz; Andrade, Marília dos Santos; Quadros, Abrahão Augusto Juviniano; Oliveira, Acary Souza Bulle; da Silva, Antonio Carlos

    2013-01-01

    OBJECTIVE: To compare lung function between patients with post-poliomyelitis syndrome and those with sequelae of paralytic poliomyelitis (without any signs or symptoms of post-poliomyelitis syndrome), as well as between patients with post-poliomyelitis syndrome and healthy controls. METHODS: Twenty-nine male participants were assigned to one of three groups: control; poliomyelitis (comprising patients who had had paralytic poliomyelitis but had not developed post-poliomyelitis syndrome); and post-poliomyelitis syndrome. Volunteers underwent lung function measurements (spirometry and respiratory muscle strength assessment). RESULTS: The results of the spirometric assessment revealed no significant differences among the groups except for an approximately 27% lower mean maximal voluntary ventilation in the post-poliomyelitis syndrome group when compared with the control group (p = 0.0127). Nevertheless, the maximal voluntary ventilation values for the post-poliomyelitis group were compared with those for the Brazilian population and were found to be normal. No significant differences were observed in respiratory muscle strength among the groups. CONCLUSIONS: With the exception of lower maximal voluntary ventilation, there was no significant lung function impairment in outpatients diagnosed with post-poliomyelitis syndrome when compared with healthy subjects and with patients with sequelae of poliomyelitis without post-poliomyelitis syndrome. This is an important clinical finding because it shows that patients with post-poliomyelitis syndrome can have preserved lung function. PMID:24068267

  4. Effects of Exposure to Welding Fume on Lung Function: Results from the German WELDOX Study.

    PubMed

    Lehnert, M; Hoffmeyer, F; Gawrych, K; Lotz, A; Heinze, E; Berresheim, H; Merget, R; Harth, V; Van Gelder, R; Hahn, J-U; Hartwig, A; Weiß, T; Pesch, B; Brüning, T

    2015-01-01

    The association between exposure to welding fume and chronic obstructive pulmonary disease (COPD) has been insufficiently clarified. In this study we assessed the influence of exposure to welding fume on lung function parameters. We investigated forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC, and expiratory flow rates in 219 welders. We measured current exposure to respirable particles and estimated a worker's lifetime exposure considering welding techniques, working conditions and protective measures at current and former workplaces. Multiple regression models were applied to estimate the influence of exposure to welding fume, age, and smoking on lung function. We additionally investigated the duration of working as a welder and the predominant welding technique. The findings were that age- and smoking-adjusted lung function parameters showed no decline with increasing duration, current exposure level, and lifetime exposure to welding fume. However, 15% of the welders had FEV1/FVC below the lower limit of normal, but we could not substantiate the presence of an association with the measures of exposure. Adverse effects of cigarette smoking were confirmed. In conclusion, the study did not support the notion of a possible detrimental effect of exposure to welding fume on lung function in welders.

  5. Environmental exposures, lung function, and respiratory health in rural Lao PDR.

    PubMed

    Lopez, Jaime R; Somsamouth, Khamphithoune; Mounivong, Boualoy; Sinclair, Ryan; Soret, Sam; Knutsen, Synnove; Singh, Pramil N

    2014-01-01

    Although the individual contributions of smoked tobacco and indoor air pollution have been identified, there are very few studies that have characterized and measured the effects of inhaled particles from a wide range of personal, household, and community practices common in rural Asia. The objective of our study was to examine the association between environmental inhaled exposures and lung function among rural males of Lao PDR. In a sample of 92 males from rural Lao PDR, study subjects completed a survey on household exposures, a physical exam, and the following measures of lung function: FEV1, FVC, and the ratio of FEV1/FVC. Our findings were as follows: a) > 80% of the subjects were exposed to indoor cooking fires (wood fuel), animal handling, dust and dirt; b) 57.6% of subjects were in the impaired range (FEV1/FVC < 0.7); and c) animal handling was negatively associated (p < 0.03) with FEV1 and FVC. Among males in rural Lao PDR, we found a high prevalence of chronic exposure to inhaled particles (animal handling, dust/dirt, smoke) and a high prevalence of impaired lung function. Findings from this pilot study indicate that associations between exposure to multiple sources of particulate matter common in rural areas and lung function need further investigation.

  6. Diesel Exhaust Modulates Ozone-induced Lung Function Decrements in Healthy Human Volunteers

    EPA Science Inventory

    The potential effects of combinations of dilute whole diesel exhaust (DE) and ozone (03), each a common component of ambient airborne pollutant mixtures, on lung function were examined. Healthy young human volunteers were exposed for 2 hr to pollutants while exercising (~50 L/min...

  7. Impact of Four-Dimensional Computed Tomography Pulmonary Ventilation Imaging-Based Functional Avoidance for Lung Cancer Radiotherapy

    SciTech Connect

    Yamamoto, Tokihiro; Kabus, Sven; Berg, Jens von; Lorenz, Cristian; Keall, Paul J.

    2011-01-01

    Purpose: To quantify the dosimetric impact of four-dimensional computed tomography (4D-CT) pulmonary ventilation imaging-based functional treatment planning that avoids high-functional lung regions. Methods and Materials: 4D-CT ventilation images were created from 15 non-small-cell lung cancer patients using deformable image registration and quantitative analysis of the resultant displacement vector field. For each patient, anatomic and functional plans were created for intensity-modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT). Consistent beam angles and dose-volume constraints were used for all cases. The plans with Radiation Therapy Oncology Group (RTOG) 0617-defined major deviations were modified until clinically acceptable. Functional planning spared the high-functional lung, and anatomic planning treated the lungs as uniformly functional. We quantified the impact of functional planning compared with anatomic planning using the two- or one-tailed t test. Results: Functional planning led to significant reductions in the high-functional lung dose, without significantly increasing other critical organ doses, but at the expense of significantly degraded the planning target volume (PTV) conformity and homogeneity. The average reduction in the high-functional lung mean dose was 1.8 Gy for IMRT (p < .001) and 2.0 Gy for VMAT (p < .001). Significantly larger changes occurred in the metrics for patients with a larger amount of high-functional lung adjacent to the PTV. Conclusion: The results of the present study have demonstrated the impact of 4D-CT ventilation imaging-based functional planning for IMRT and VMAT for the first time. Our findings indicate the potential of functional planning in lung functional avoidance for both IMRT and VMAT, particularly for patients who have high-functional lung adjacent to the PTV.

  8. Investigation of Lung Structure-Function Relationships Using Hyperpolarized Noble Gases

    NASA Astrophysics Data System (ADS)

    Thomen, Robert P.

    Magnetic Resonance Imaging (MRI) is an application of the nuclear magnetic resonance (NMR) phenomenon to non-invasively generate 3D tomographic images. MRI is an emerging modality for the lung, but it suffers from low sensitivity due to inherent low tissue density and short T(*/2) . Hyperpolarization is a process by which the nuclear contribution to NMR signal is greatly enhanced to more than 100,000 times that of samples in thermal equilibrium. The noble gases 3He and 129Xe are most often hyperpolarized by transfer of light angular momentum through the electron of a vaporized alkali metal to the noble gas nucleus (called Spin Exchange Optical Pumping). The enhancement in NMR signal is so great that the gas itself can be imaged via MRI, and because noble gases are chemically inert, they can be safely inhaled by a subject, and the gas distribution within the interior of the lung can be imaged. The mechanics of respiration is an elegant physical process by which air is is brought into the distal airspaces of the lungs for oxygen/carbon dioxide gas exchange with blood. Therefore proper description of lung function is intricately related to its physical structure , and the basic mechanical operation of healthy lungs -- from pressure driven airflow, to alveolar airspace gas kinetics, to gas exchange by blood/gas concentration gradients, to elastic contraction of parenchymal tissue -- is a process decidedly governed by the laws of physics. This dissertation will describe experiments investigating the relationship of lung structure and function using hyperpolarized (HP) noble gas MRI. In particular HP gases will be applied to the study of several pulmonary diseases each of which demonstrates unique structure-function abnormalities: asthma, cystic fibrosis, and chronic obstructive pulmonary disease. Successful implementation of an HP gas acquisition protocol for pulmonary studies is an involved and stratified undertaking which requires a solid theoretical foundation in NMR

  9. Impact of hydrogel nanoparticle size and functionalization on in vivo behavior for lung imaging and therapeutics

    PubMed Central

    Liu, Yongjian; Ibricevic-Richardson, Aida; Cohen, Joel A.; Cohen, Jessica L.; Gunsten, Sean P.; Fréchet, Jean M. J.; Walter, Michael J.; Welch, Michael J.; Brody, Steven L.

    2009-01-01

    Polymer chemistry offers the possibility of synthesizing multifunctional nanoparticles which incorporate moieties that enhance diagnostic and therapeutic targeting of cargo delivery to the lung. However, since rules for predicting particle behavior following modification are not well defined, it is essential that probes for tracking fate in vivo are also included. Accordingly, we designed polyacrylamide-based hydrogel particles of differing sizes, functionalized with a nona-arginine cell-penetrating peptide (Arg9), and labeled with imaging components to assess lung retention and cellular uptake after intratracheal administration. Radiolabeled microparticles (1–5 µm diameter) and nanoparticles (20–40 nm diameter) without and with Arg9 showed diffuse airspace distribution by positron emission tomography imaging. Biodistribution studies revealed that particle clearance and extrapulmonary distribution was, in part, size dependent. Microparticles were rapidly cleared by mucociliary routes but unexpectedly, also through the circulation. In contrast, nanoparticles had prolonged lung retention enhanced by Arg9 and were significantly restricted to the lung. For all particle types, uptake was predominant in alveolar macrophages, and, to a lesser extent, lung epithelial cells. In general, particles did not induce local inflammatory responses, with the exception of microparticles bearing Arg9. Whereas microparticles may be advantageous for short-term applications, nano-sized particles constitute an efficient high-retention and non-inflammatory vehicle for the delivery of diagnostic imaging agents and therapeutics to lung airspaces and alveolar macrophages that can be enhanced by Arg9. Importantly, our results show that minor particle modifications may significantly impact in vivo behavior within the complex environments of the lung, underscoring the need for animal modeling. PMID:19852512

  10. Chronic Alcohol Ingestion in Rats Alters Lung Metabolism, Promotes Lipid Accumulation, and Impairs Alveolar Macrophage Functions

    PubMed Central

    Romero, Freddy; Shah, Dilip; Duong, Michelle; Stafstrom, William; Hoek, Jan B.; Kallen, Caleb B.; Lang, Charles H.

    2014-01-01

    Chronic alcoholism impairs pulmonary immune homeostasis and predisposes to inflammatory lung diseases, including infectious pneumonia and acute respiratory distress syndrome. Although alcoholism has been shown to alter hepatic metabolism, leading to lipid accumulation, hepatitis, and, eventually, cirrhosis, the effects of alcohol on pulmonary metabolism remain largely unknown. Because both the lung and the liver actively engage in lipid synthesis, we hypothesized that chronic alcoholism would impair pulmonary metabolic homeostasis in ways similar to its effects in the liver. We reasoned that perturbations in lipid metabolism might contribute to the impaired pulmonary immunity observed in people who chronically consume alcohol. We studied the metabolic consequences of chronic alcohol consumption in rat lungs in vivo and in alveolar epithelial type II cells and alveolar macrophages (AMs) in vitro. We found that chronic alcohol ingestion significantly alters lung metabolic homeostasis, inhibiting AMP-activated protein kinase, increasing lipid synthesis, and suppressing the expression of genes essential to metabolizing fatty acids (FAs). Furthermore, we show that these metabolic alterations promoted a lung phenotype that is reminiscent of alcoholic fatty liver and is characterized by marked accumulation of triglycerides and free FAs within distal airspaces, AMs, and, to a lesser extent, alveolar epithelial type II cells. We provide evidence that the metabolic alterations in alcohol-exposed rats are mechanistically linked to immune impairments in the alcoholic lung: the elevations in FAs alter AM phenotypes and suppress both phagocytic functions and agonist-induced inflammatory responses. In summary, our work demonstrates that chronic alcohol ingestion impairs lung metabolic homeostasis and promotes pulmonary immune dysfunction. These findings suggest that therapies aimed at reversing alcohol-related metabolic alterations might be effective for preventing and

  11. Exploring the mechanical basis for acceleration: pelvic limb locomotor function during accelerations in racing greyhounds (Canis familiaris).

    PubMed

    Williams, S B; Usherwood, J R; Jespers, K; Channon, A J; Wilson, A M

    2009-02-01

    Animals in their natural environments are confronted with a regular need to perform rapid accelerations (for example when escaping from predators or chasing prey). Such acceleration requires net positive mechanical work to be performed on the centre of mass by skeletal muscle. Here we determined how pelvic limb joints contribute to the mechanical work and power that are required for acceleration in galloping quadrupeds. In addition, we considered what, if any, biomechanical strategies exist to enable effective acceleration to be achieved. Simultaneous kinematic and kinetic data were collected for racing greyhounds undergoing a range of low to high accelerations. From these data, joint moments and joint powers were calculated for individual hindlimb joints. In addition, the mean effective mechanical advantage (EMA) of the limb and the ;gear ratio' of each joint throughout stance were calculated. Greatest increases in joint work and power with acceleration appeared at the hip and hock joints, particularly in the lead limb. Largest increases in absolute positive joint work occurred at the hip, consistent with the hypothesis that quadrupeds power locomotion by torque about the hip. In addition, hindlimb EMA decreased substantially with increased acceleration - a potential strategy to increase stance time and thus ground impulses for a given peak force. This mechanism may also increase the mechanical advantage for applying the horizontal forces necessary for acceleration.

  12. Poster — Thur Eve — 31: Dosimetric Effect of Respiratory Motion on RapidArc Lung SBRT Treatment Delivered by TrueBeam Linear Accelerator

    SciTech Connect

    Jiang, Runqing; Zhan, Lixin; Osei, Ernest

    2014-08-15

    Volumetric modulated arc therapy (VMAT) allows fast delivery of stereotactic radiotherapy. However, the discrepancies between the calculated and delivered dose distributions due to respiratory motion and dynamic multileaf collimators (MLCs) interplay are not avoidable. The purpose of this study is to investigate RapidArc lung SBRT treatment delivered by the flattening filter-free (FFF) beam and flattened beam with Varian TrueBeam machine. CIRS Dynamic Thorax Phantom with in-house made lung tumor insertion was CT scanned both in free breathing and 4DCT. 4DCT was used to determine the internal target volume. The free breathing CT scan was used for treatment planning. A 5 mm margin was given to ITV to generate a planning target volume. Varian Eclipse treatment planning was used to generate RapidArc plans based on the 6 MV flattened beam and 6MV FFF beam. The prescription dose was 48 Gy in 4 fractions. At least 95% of PTV was covered by the prescribed dose. The RapidArc plans with 6 MV flattened beam and 6MV FFF beam were delivered with Varian TrueBeam machine. The dosimetric measurements were performed with Gafchromic XR-RV3 film, which was placed in the lung tumor insertion. The interplay between the dynamic MLC-based delivery of VMAT and the respiratory motion of the tumor degraded target coverage and created undesired hot or cold dose spots inside the lung tumor. Lung SBRT RapidArc treatments delivered by the FFF beam of TrueBeam linear accelerator is superior to the flattened beam. Further investigation will be performed by Monte Carlo simulation.

  13. Dual bronchodilation in COPD: lung function and patient-reported outcomes - a review.

    PubMed

    Price, David; Østrem, Anders; Thomas, Mike; Welte, Tobias

    2017-01-01

    Several fixed-dose combinations (FDCs) of long-acting bronchodilators (a long-acting muscarinic antagonist [LAMA] plus a long-acting β2-agonist [LABA]) are available for the treatment of COPD. Studies of these FDCs have demonstrated substantial improvements in lung function (forced expiratory volume in 1 second) in comparison with their respective constituent monocomponents. Improvements in patient-reported outcomes (PROs), such as symptoms and health status, as well as exacerbation rates, have been reported compared with a LABA or LAMA alone, but results are less consistent. The inconsistencies may in part be owing to differences in study design, methods used to assess study end points, and patient populations. Nevertheless, these observations tend to support an association between improvements in forced expiratory volume in 1 second and improvements in symptom-based outcomes. In order to assess the effects of FDCs on PROs and evaluate relationships between PROs and changes in lung function, we performed a systematic literature search of publications reporting randomized controlled trials of FDCs. Results of this literature search were independently assessed by two reviewers, with a third reviewer resolving any conflicting results. In total, 22 Phase III randomized controlled trials of FDC bronchodilators in COPD were identified, with an additional study including a post-literature search (ten for indacaterol-glycopyrronium once daily, eight for umeclidinium-vilanterol once daily, three for tiotropium-olodaterol once daily, and two for aclidinium-formoterol twice daily). Results from these studies demonstrated that the LAMA-LABA FDCs significantly improved lung function compared with their component monotherapies or other single-agent treatments. Furthermore, LABA-LAMA combinations also generally improved symptoms and health status versus monotherapies, although some discrepancies between lung function and PROs were observed. Overall, the safety profiles of the

  14. Indoor nitrous acid and respiratory symptoms and lung function in adults

    PubMed Central

    Jarvis, D; Leaderer, B; Chinn, S; Burney, P

    2005-01-01

    Background: Nitrogen dioxide (NO2) is an important pollutant of indoor and outdoor air, but epidemiological studies show inconsistent health effects. These inconsistencies may be due to failure to account for the health effects of nitrous acid (HONO) which is generated directly from gas combustion and indirectly from NO2. Methods: Two hundred and seventy six adults provided information on respiratory symptoms and lung function and had home levels of NO2 and HONO measured as well as outdoor levels of NO2. The association of indoor HONO levels with symptoms and lung function was examined. Results: The median indoor HONO level was 3.10 ppb (IQR 2.05–5.09), with higher levels in homes with gas hobs, gas ovens, and in those measured during the winter months. Non-significant increases in respiratory symptoms were observed in those living in homes with higher HONO levels. An increase of 1 ppb in indoor HONO was associated with a decrease in forced expiratory volume in 1 second (FEV1) percentage predicted (–0.96%; 95% CI –0.09 to –1.82) and a decrease in percentage FEV1/forced vital capacity (FVC) (–0.45%; 95% CI –0.06 to –0.83) after adjustment for relevant confounders. Measures of indoor NO2 were correlated with HONO (r = 0.77), but no significant association of indoor NO2 with symptoms or lung function was observed. After adjustment for NO2 measures, the association of HONO with low lung function persisted. Conclusion: Indoor HONO levels are associated with decrements in lung function and possibly with more respiratory symptoms. Inconsistencies between studies examining health effects of NO2 and use of gas appliances may be related to failure to account for this association. PMID:15923247

  15. Dual bronchodilation in COPD: lung function and patient-reported outcomes – a review

    PubMed Central

    Price, David; Østrem, Anders; Thomas, Mike; Welte, Tobias

    2017-01-01

    Several fixed-dose combinations (FDCs) of long-acting bronchodilators (a long-acting muscarinic antagonist [LAMA] plus a long-acting β2-agonist [LABA]) are available for the treatment of COPD. Studies of these FDCs have demonstrated substantial improvements in lung function (forced expiratory volume in 1 second) in comparison with their respective constituent monocomponents. Improvements in patient-reported outcomes (PROs), such as symptoms and health status, as well as exacerbation rates, have been reported compared with a LABA or LAMA alone, but results are less consistent. The inconsistencies may in part be owing to differences in study design, methods used to assess study end points, and patient populations. Nevertheless, these observations tend to support an association between improvements in forced expiratory volume in 1 second and improvements in symptom-based outcomes. In order to assess the effects of FDCs on PROs and evaluate relationships between PROs and changes in lung function, we performed a systematic literature search of publications reporting randomized controlled trials of FDCs. Results of this literature search were independently assessed by two reviewers, with a third reviewer resolving any conflicting results. In total, 22 Phase III randomized controlled trials of FDC bronchodilators in COPD were identified, with an additional study including a post-literature search (ten for indacaterol–glycopyrronium once daily, eight for umeclidinium–vilanterol once daily, three for tiotropium–olodaterol once daily, and two for aclidinium–formoterol twice daily). Results from these studies demonstrated that the LAMA–LABA FDCs significantly improved lung function compared with their component monotherapies or other single-agent treatments. Furthermore, LABA–LAMA combinations also generally improved symptoms and health status versus monotherapies, although some discrepancies between lung function and PROs were observed. Overall, the safety

  16. Genetic variation in HTR4 and lung function: GWAS follow-up in mouse.

    PubMed

    House, John S; Li, Huiling; DeGraff, Laura M; Flake, Gordon; Zeldin, Darryl C; London, Stephanie J

    2015-01-01

    Human genome-wide association studies (GWASs) have identified numerous associations between single nucleotide polymorphisms (SNPs) and pulmonary function. Proving that there is a causal relationship between GWAS SNPs, many of which are noncoding and without known functional impact, and these traits has been elusive. Furthermore, noncoding GWAS-identified SNPs may exert trans-regulatory effects rather than impact the proximal gene. Noncoding variants in 5-hydroxytryptamine (serotonin) receptor 4 (HTR4) are associated with pulmonary function in human GWASs. To gain insight into whether this association is causal, we tested whether Htr4-null mice have altered pulmonary function. We found that HTR4-deficient mice have 12% higher baseline lung resistance and also increased methacholine-induced airway hyperresponsiveness (AHR) as measured by lung resistance (27%), tissue resistance (48%), and tissue elastance (30%). Furthermore, Htr4-null mice were more sensitive to serotonin-induced AHR. In models of exposure to bacterial lipopolysaccharide, bleomycin, and allergic airway inflammation induced by house dust mites, pulmonary function and cytokine profiles in Htr4-null mice differed little from their wild-type controls. The findings of altered baseline lung function and increased AHR in Htr4-null mice support a causal relationship between genetic variation in HTR4 and pulmonary function identified in human GWAS.

  17. Electron distribution function behavior during localized transverse ion acceleration events in the topside auroral zone

    NASA Technical Reports Server (NTRS)

    Lynch, K. A.; Arnoldy, R. L.; Kintner, P. M.; Vago, J. L.

    1994-01-01

    The Topaz3 auroral sounding rocket made the following observations concerning the transfer of precipitating auroral electron energy to transverse ion acceleration in the topside auroral zone. During the course of the flight, the precipitating electron beam was modified to varying degrees by interaction with VLF hiss, at times changing the beam into a field-aligned plateau. The electron distribution functions throughout the flight are classified according to the extent of this modification, and correspondences with ion acceleration events are sought. The hiss power during most of this rocket flight apparently exceeded the threshold for collapse into solitary structures. At the times of plateaued electron distributions, the collapse of these structures was limited by Landau damping through the ambient ions, resulting in a velocity-dependent acceleration of both protons and oxygen. This initial acceleration is sufficient to supply the number flux of upflowing ions observed at satellite altitudes. The bursty ion acceleration was anticorrelated, on 1-s or smaller timescales, with dispersive bursts of precipitating field-aligned electrons, although on longer timescales the bursty ions and the bursty electrons are correlated.

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

    PubMed Central

    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

  19. Brain but not lung functions impaired after a chlorine incident.

    PubMed

    Kilburn, Kaye H

    2003-10-01

    A workplace bleach exposure incident was studied in 13 women to determine whether chlorine caused neurobehavioral and pulmonary functional effects. We compared neurophysiological and neuropsychological measurements in 13 chlorine-exposed women, 4.5 years after exposure, and 41 unexposed women. Reaction times, balance, blink reflex latency, color discrimination and several psychological tests were measured. Pulmonary function was assessed by spirometry. A profile of mood states and frequencies of 35 symptoms were obtained. Chlorine exposed women performed statistically significantly below unexposed women for simple and choice reaction times, balance with eyes open and eyes closed, color discrimination, grip strength, Culture Fair, digit symbol substitution, vocabulary, trail making B and pegboard. Profile of mood states scores and frequency symptoms were elevated. Respiratory symptoms were elevated but pulmonary volumes and flows were not reduced. Chlorine bleach exposure was associated with impaired neurobehavioral functions and elevated POMS scores and symptom frequencies. Alternatives to chlorine should be used.

  20. Birth weight at term and lung function in adolescence: no evidence for a programmed effect.

    PubMed Central

    Matthes, J W; Lewis, P A; Davies, D P; Bethel, J A

    1995-01-01

    It has been suggested that factors which influence low birth weight at term may be associated with reduced lung function in later life. This hypothesis was investigated in a comparative (retrospective) cohort study of 164 matched pairs of subjects where the observers responsible for tracing and studying the subjects were unaware of their case or control status. The subjects, born in Cardiff between 1975 and 1977, were of mean age 15.7 years. Cases (low birth weight (< 2500 g) at term) were matched with controls (normal birth weight (3000-3800 g) at term) for sex, parity, place of birth, date of birth, and gestation. Lung function was measured using a portable spirometer. The corrected mean differences (95% confidence interval) in forced vital capacity (FVC) and flow when 50% or 25% of the FVC remains in the lungs between the cases and controls were respectively -41 ml (-140 to 58), -82 ml/sec (-286 to 122), and -83 ml/sec (-250 to 83). None of these differences were statistically significant. These results are inconsistent with the hypothesis that low birth weight at term is associated with reduced lung function in adolescence. PMID:7492161

  1. Compatible solutes: ectoine and hydroxyectoine improve functional nanostructures in artificial lung surfactants.

    PubMed

    Harishchandra, Rakesh Kumar; Sachan, Amit Kumar; Kerth, Andreas; Lentzen, Georg; Neuhaus, Thorsten; Galla, Hans-Joachim

    2011-12-01

    Ectoine and hydroxyectoine belong to the family of compatible solutes and are among the most abundant osmolytes in nature. These compatible solutes protect biomolecules from extreme conditions and maintain their native function. In the present study, we have investigated the effect of ectoine and hydroxyectoine on the domain structures of artificial lung surfactant films consisting of dipalmitoylphosphatidylcholine (DPPC), dipalmitoylphosphatidylglycerol (DPPG) and the lung surfactant specific surfactant protein C (SP-C) in a molar ratio of 80:20:0.4. The pressure-area isotherms are found to be almost unchanged by both compatible solutes. The topology of the fluid domains shown by scanning force microscopy, which is thought to be responsible for the biophysical behavior under compression, however, is modified giving rise to the assumption that ectoine and hydroxyectoine are favorable for a proper lung surfactant function. This is further evidenced by the analysis of the insertion kinetics of lipid vesicles into the lipid-peptide monolayer, which is clearly enhanced in the presence of both compatible solutes. Thus, we could show that ectoine and hydroxyectoine enhance the function of lung surfactant in a simple model system, which might provide an additional rationale to inhalative therapy.

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

    PubMed

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

    1983-06-01

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

  3. Fetal corticosteroid and T4 treatment effects on lung function of surfactant-treated preterm lambs.

    PubMed

    Chen, C M; Ikegami, M; Ueda, T; Polk, D H; Jobe, A H

    1995-01-01

    Three groups of sheep fetuses at 125 or 126 d gestational age randomly received a single ultrasound-guided intramuscular injection of saline, 0.5 mg/kg betamethasone, or 0.5 mg/kg betamethasone plus 50 micrograms/kg thyroxine (T4). Forty-eight hours later the fetuses were delivered, treated with a pulmonary surfactant preparation, and ventilated for 3 h. Corticosteroids alone and in combination with T4 increased FRC, compliance, and lung volumes, and decreased the protein leak into the airspace. Saturated phosphatidylcholine pool sizes recovered by alveolar washing were not changed after hormone treatment. To evaluate the function of surfactant recovered from the lambs in vivo, we treated preterm rabbits at 27 d gestational age with the large-aggregate surfactant from alveolar washes. Large-aggregate surfactants and the pulmonary surfactant preparation increased compliances and maximal lung volumes relative to those in untreated preterm rabbits. Large-aggregate surfactants improved compliance more than did the pulmonary surfactant preparation. We conclude that ultrasound-guided single fetal corticosteroid treatment followed by postnatal surfactant improved postnatal lung function in preterm lambs. Addition of T4 did not augment corticosteroid effects. The function of the exogenous surfactant was improved in premature lamb lungs independently of the fetal treatment modality.

  4. [Pharmacological correction of central nervous system function in exposure to Coriolis acceleration].

    PubMed

    Karkishchenko, N N; Dimitriadi, N A; Molchanovskiĭ, V V

    1986-01-01

    Healthy volunteers with a low vestibular tolerance were exposed to Coriolis acceleration. Potassium orotate, pyracetame and riboxine were used as prophylactic measures against disorders in the function of the vestibular apparatus and higher compartments of the higher nervous system. The central nervous function was assessed with respect to the spectral power of electroencephalograms, short-term memory and mental performance. Potassium orotate given at a dose of 40 mg/kg body weight/day during 12-14 days as well as pyracetame given at a dose of 30 mg/kg body weight/day during 3 or 7 days increased significantly statokinetic tolerance and produced a protective effect on the central nervous function against Coriolis acceleration.

  5. Modulation of leg joint function to produce emulated acceleration during walking and running in humans

    PubMed Central

    Raiteri, Brent J.

    2017-01-01

    Understanding how humans adapt gait mechanics for a wide variety of locomotor tasks is important for inspiring the design of robotic, prosthetic and wearable assistive devices. We aimed to elicit the mechanical adjustments made to leg joint functions that are required to generate accelerative walking and running, using metrics with direct relevance to device design. Twelve healthy male participants completed constant speed (CS) walking and running and emulated acceleration (ACC) trials on an instrumented treadmill. External force and motion capture data were combined in an inverse dynamics analysis. Ankle, knee and hip joint mechanics were described and compared using angles, moments, powers and normalized functional indexes that described each joint as relatively more: spring, motor, damper or strut-like. To accelerate using a walking gait, the ankle joint was switched from predominantly spring-like to motor-like, while the hip joint was maintained as a motor, with an increase in hip motor-like function. Accelerating while running involved no change in the primary function of any leg joint, but involved high levels of spring and motor-like function at the hip and ankle joints. Mechanical adjustments for ACC walking were achieved primarily via altered limb positioning, but ACC running needed greater joint moments.

  6. Aquaporin 5 Polymorphisms and Rate of Lung Function Decline in Chronic Obstructive Pulmonary Disease

    PubMed Central

    Hansel, Nadia N.; Sidhaye, Venkataramana; Rafaels, Nicholas M.; Gao, Li; Gao, Peisong; Williams, Renaldo; Connett, John E.; Beaty, Terri H.; Mathias, Rasika A.; Wise, Robert A.; King, Landon S.; Barnes, Kathleen C.

    2010-01-01

    Rationale Aquaporin-5 (AQP5) can cause mucus overproduction and lower lung function. Genetic variants in the AQP5 gene might be associated with rate of lung function decline in chronic obstructive pulmonary disease (COPD). Methods Five single nucleotide polymorphisms (SNPs) in AQP5 were genotyped in 429 European American individuals with COPD randomly selected from the NHLBI Lung Health Study. Mean annual decline in FEV1 % predicted, assessed over five years, was calculated as a linear regression slope, adjusting for potential covariates and stratified by smoking status. Constructs containing the wildtype allele and risk allele of the coding SNP N228K were generated using site-directed mutagenesis, and transfected into HBE-16 (human bronchial epithelial cell line). AQP5 abundance and localization were assessed by immunoblots and confocal immunofluoresence under control, shear stress and cigarette smoke extract (CSE 10%) exposed conditions to test for differential expression or localization. Results Among continuous smokers, three of the five SNPs tested showed significant associations (0.02>P>0.004) with rate of lung function decline; no associations were observed among the group of intermittent or former smokers. Haplotype tests revealed multiple association signals (0.012>P>0.0008) consistent with the single-SNP results. In HBE16 cells, shear stress and CSE led to a decrease in AQP5 abundance in the wild-type, but not in the N228K AQP5 plasmid. Conclusions Polymorphisms in AQP5 were associated with rate of lung function decline in continuous smokers with COPD. A missense mutation modulates AQP-5 expression in response to cigarette smoke extract and shear stress. These results suggest that AQP5 may be an important candidate gene for COPD. PMID:21151978

  7. Lung function in the absence of respiratory symptoms in overweight children and adolescents*

    PubMed Central

    de Assunção, Silvana Neves Ferraz; Daltro, Carla Hilário da Cunha; Boa Sorte, Ney Christian; Ribeiro, Hugo da Costa; Bastos, Maria de Lourdes; Queiroz, Cleriston Farias; Lemos, Antônio Carlos Moreira

    2014-01-01

    OBJECTIVE: To describe lung function findings in overweight children and adolescents without respiratory disease. METHODS: This was a cross-sectional study involving male and female overweight children and adolescents in the 8-18 year age bracket, without respiratory disease. All of the participants underwent anthropometric assessment, chest X-ray, pulse oximetry, spirometry, and lung volume measurements. Individuals with respiratory disease were excluded, as were those who were smokers, those with abnormal chest X-rays, and those with an SpO2 = 92%. Waist circumference was measured in centimeters. The body mass index-for-age Z score for boys and girls was used in order to classify the individuals as overweight, obese, or severely obese. Lung function variables were expressed in percentage of the predicted value and were correlated with the anthropometric indices. RESULTS: We included 59 individuals (30 males and 29 females). The mean age was 11.7 ± 2.7 years. Lung function was normal in 21 individuals (35.6%). Of the 38 remaining individuals, 19 (32.2%), 15 (25.4%), and 4 (6.7%) presented with obstructive, restrictive, and mixed ventilatory disorder, respectively. The bronchodilator response was positive in 15 individuals (25.4%), and TLC measurements revealed that all of the individuals with reduced VC had restrictive ventilatory disorder. There were significant negative correlations between the anthropometric indices and the Tiffeneau index in the individuals with mixed ventilatory disorder. CONCLUSIONS: Lung function was abnormal in approximately 65% of the individuals evaluated here, all of whom were overweight. Obstructive ventilatory disorder and positive bronchodilator response predominated. PMID:24831397

  8. Influence of Radiofrequency Ablation of Lung Cancer on Pulmonary Function

    SciTech Connect

    Tada, Akihiro Hiraki, Takao; Iguchi, Toshihiro; Gobara, Hideo; Mimura, Hidefumi; Toyooka, Shinichi; Kiura, Katsuyuki; Tsuda, Toshihide; Mitsuhashi, Toshiharu; Kanazawa, Susumu

    2012-08-15

    Purpose: The purpose of this study was to evaluate altered pulmonary function retrospectively after RFA. Methods: This retrospective study comprised 41 ablation sessions for 39 patients (22 men and 17 women; mean age, 64.8 years). Vital capacity (VC) and forced expiratory volume in 1 s (FEV{sub 1}) at 1 and 3 months after RFA were compared with the baseline (i.e., values before RFA). To evaluate the factors that influenced impaired pulmonary function, univariate analysis was performed by using multiple variables. If two or more variables were indicated as statistically significant by univariate analysis, these variables were subjected to multivariate analysis to identify independent factors. Results: The mean VC and FEV{sub 1} before RFA and 1 and 3 months after RFA were 3.04 and 2.24 l, 2.79 and 2.11 l, and 2.85 and 2.13 l, respectively. The values at 1 and 3 months were significantly lower than the baseline. Severe pleuritis after RFA was identified as the independent factor influencing impaired VC at 1 month (P = 0.003). For impaired FEV{sub 1} at 1 month, only severe pleuritis (P = 0.01) was statistically significant by univariate analysis. At 3 months, severe pleuritis (VC, P = 0.019; FEV{sub 1}, P = 0.003) and an ablated parenchymal volume {>=}20 cm{sup 3} (VC, P = 0.047; FEV{sub 1}, P = 0.038) were independent factors for impaired VC and FEV{sub 1}. Conclusions: Pulmonary function decreased after RFA. RFA-induced severe pleuritis and ablation of a large volume of marginal parenchyma were associated with impaired pulmonary function.

  9. Air pollution and lung function among susceptible adult subjects: a panel study

    PubMed Central

    Lagorio, Susanna; Forastiere, Francesco; Pistelli, Riccardo; Iavarone, Ivano; Michelozzi, Paola; Fano, Valeria; Marconi, Achille; Ziemacki, Giovanni; Ostro, Bart D

    2006-01-01

    Background Adverse health effects at relatively low levels of ambient air pollution have consistently been reported in the last years. We conducted a time-series panel study of subjects with chronic obstructive pulmonary disease (COPD), asthma, and ischemic heart disease (IHD) to evaluate whether daily levels of air pollutants have a measurable impact on the lung function of adult subjects with pre-existing lung or heart diseases. Methods Twenty-nine patients with COPD, asthma, or IHD underwent repeated lung function tests by supervised spirometry in two one-month surveys. Daily samples of coarse (PM10–2.5) and fine (PM2.5) particulate matter were collected by means of dichotomous samplers, and the dust was gravimetrically analyzed. The particulate content of selected metals (cadmium, chrome, iron, nickel, lead, platinum, vanadium, and zinc) was determined by atomic absorption spectrometry. Ambient concentrations of nitrogen dioxide (NO2), carbon monoxide (CO), ozone (O3), and sulphur dioxide (SO2) were obtained from the regional air-quality monitoring network. The relationships between concentrations of air pollutants and lung function parameters were analyzed by generalized estimating equations (GEE) for panel data. Results Decrements in lung function indices (FVC and/or FEV1) associated with increasing concentrations of PM2.5, NO2 and some metals (especially zinc and iron) were observed in COPD cases. Among the asthmatics, NO2 was associated with a decrease in FEV1. No association between average ambient concentrations of any air pollutant and lung function was observed among IHD cases. Conclusion This study suggests that the short-term negative impact of exposure to air pollutants on respiratory volume and flow is limited to individuals with already impaired respiratory function. The fine fraction of ambient PM seems responsible for the observed effects among COPD cases, with zinc and iron having a potential role via oxidative stress. The respiratory function

  10. Accelerated remyelination during inflammatory demyelination prevents axonal loss and improves functional recovery

    PubMed Central

    Mei, Feng; Lehmann-Horn, Klaus; Shen, Yun-An A; Rankin, Kelsey A; Stebbins, Karin J; Lorrain, Daniel S; Pekarek, Kara; A Sagan, Sharon; Xiao, Lan; Teuscher, Cory; von Büdingen, H-Christian; Wess, Jürgen; Lawrence, J Josh; Green, Ari J; Fancy, Stephen PJ; Zamvil, Scott S; Chan, Jonah R

    2016-01-01

    Demyelination in MS disrupts nerve signals and contributes to axon degeneration. While remyelination promises to restore lost function, it remains unclear whether remyelination will prevent axonal loss. Inflammatory demyelination is accompanied by significant neuronal loss in the experimental autoimmune encephalomyelitis (EAE) mouse model and evidence for remyelination in this model is complicated by ongoing inflammation, degeneration and possible remyelination. Demonstrating the functional significance of remyelination necessitates selectively altering the timing of remyelination relative to inflammation and degeneration. We demonstrate accelerated remyelination after EAE induction by direct lineage analysis and hypothesize that newly formed myelin remains stable at the height of inflammation due in part to the absence of MOG expression in immature myelin. Oligodendroglial-specific genetic ablation of the M1 muscarinic receptor, a potent negative regulator of oligodendrocyte differentiation and myelination, results in accelerated remyelination, preventing axonal loss and improving functional recovery. Together our findings demonstrate that accelerated remyelination supports axonal integrity and neuronal function after inflammatory demyelination. DOI: http://dx.doi.org/10.7554/eLife.18246.001 PMID:27671734

  11. Serum p53 antibody detection in patients with impaired lung function

    PubMed Central

    2013-01-01

    Background TP53 gene mutations can lead to the expression of a dysfunctional protein that in turn may enable genetically unstable cells to survive and change into malignant cells. Mutant p53 accumulates early in cells and can precociously induce circulating anti-p53 antibodies (p53Abs); in fact, p53 overexpression has been observed in pre-neoplastic lesions, such as bronchial dysplasia, and p53Abs have been found in patients with Chronic Obstructive Pulmonary Disease, before the diagnosis of lung and other tobacco-related tumors. Methods A large prospective study was carried out, enrolling non-smokers, ex-smokers and smokers with or without the impairment of lung function, to analyze the incidence of serum p53Abs and the correlation with clinicopathologic features, in particular smoking habits and impairment of lung function, in order to investigate their possible role as early markers of the onset of lung cancer or other cancers. The p53Ab levels were evaluated by a specific ELISA in 675 subjects. Results Data showed that significant levels of serum p53Abs were present in 35 subjects (5.2%); no difference was observed in the presence of p53Abs with regard to age and gender, while p53Abs correlated with the number of cigarettes smoked per day and packs-year. Furthermore, serum p53Abs were associated with the worst lung function impairment. The median p53Ab level in positive subjects was 3.5 units/ml (range 1.2 to 65.3 units/ml). Only fifteen positive subjects participated in the follow-up, again resulting positive for serum p53Abs, and no evidence of cancer was found in these patients. Conclusion The presence of serum p53Abs was found to be associated with smoking level and lung function impairment, both risk factors of cancer development. However, in our study we have not observed the occurrence of lung cancer or other cancers in the follow-up of positive subjects, therefore we cannot directly correlate the presence of serum p53Abs with cancer risk. PMID:23384026

  12. SUSD2 is frequently downregulated and functions as a tumor suppressor in RCC and lung cancer.

    PubMed

    Cheng, Yingying; Wang, Xiaolin; Wang, Pingzhang; Li, Ting; Hu, Fengzhan; Liu, Qiang; Yang, Fan; Wang, Jun; Xu, Tao; Han, Wenling

    2016-07-01

    Sushi domain containing 2 (SUSD2) is type I membrane protein containing domains inherent to adhesion molecules. There have been few reported studies on SUSD2, and they have mainly focused on breast cancer, colon cancer, and HeLa cells. However, the expression and function of SUSD2 in other cancers remain unclear. In the present study, we conducted an integrated bioinformatics analysis based on the array data from the GEO database and found a significant downregulation of SUSD2 in renal cell carcinoma (RCC) and lung cancer. Western blotting and quantitative RT-PCR (qRT-PCR) confirmed that SUSD2 was frequently decreased in RCC and lung cancer tissues compared with the corresponding levels in normal adjacent tissues. The restoration of SUSD2 expression inhibited the proliferation and clonogenicity of RCC and lung cancer cells, whereas the knockdown of SUSD2 promoted A549 cell growth. Our findings suggested that SUSD2 functions as a tumor suppressor gene (TSG) in RCC and lung cancer.

  13. Cardiopulmonary function and morphologic changes in beagle dogs after multiple lung lavages

    SciTech Connect

    Muggenburg, B.A.; Mauderly, J.L.; Halliwell, W.H.; Slauson, D.O.

    1980-03-01

    This study evaluated the long-term biomedical risks of multiple, massive saline lung lavage using dogs. Risks were assessed using clinical examinations of cardiopulmonary function, thoracic radiographs, auscultation of the chest, body temperature, and hematologic values. Thirty-six dogs given 10 lavages over a 49-day period had no gross lesions at time of necropsy 7 days after the last lavage. Six dogs, followed with clinical examinations after each of 10 lung lavages, had no detectable effects from the lavage except for elevated body temperature and bronchial breathing at 24 hr after some procedures. No gross lesions were found at sacrifice 28 days after the last lavage. The only histologic lesions found were those also found in unlavaged control dogs. Six dogs that were lavaged 10 or more times had normal pulmonary function values for 4 yr after the last lung lavage. No chronic sequelae were found in healthy beagle dogs given 10 or more lung lavages suggesting a minimal long-term risk associated with these procedures.

  14. Normalization of Lung Function Following Treatment of Secondary Usual Interstitial Pneumonia: A Case Report

    PubMed Central

    Hohberger, Laurie A; Montero-Arias, Felicia; Roden, Anja C; Vassallo, Robert

    2015-01-01

    Usual interstitial pneumonia (UIP) is the most common idiopathic interstitial pneumonia (IIP) and is associated with a poor prognosis and poor responsiveness to immunosuppressive therapy. We present a case of a woman with steroid-responsive biopsy-proven UIP with significant and sustained improvement in pulmonary function. A female in her 40s presented following a one-year history of progressive dyspnea, a 20 lb weight loss, and fatigue. Imaging of the chest with computed tomography (CT) showed bibasilar subpleural reticular opacities and minimal peripheral honeycombing. Comprehensive connective tissue disease (CTD) antibody testing was negative. Pulmonary function testing showed moderate impairment with reduction in forced vital capacity (FVC, 69% predicted), forced expiratory volume in one second (FEV1 73% predicted), and diffusing capacity for carbon monoxide (DLCO, 52% predicted). Surgical lung biopsy showed UIP with prominent inflammatory infiltrates. Following treatment with prednisone and azathioprine, the patient’s symptoms resolved, while objective pulmonary function testing showed normalization of lung function, which is sustained at >4 years of follow-up. Improvement in lung function following immunosuppressive therapy is distinctly uncommon in either idiopathic or secondary UIP. This report suggests that occasionally, patients with secondary UIP occurring in the context of otherwise undefinable autoimmune clinical syndromes may be responsive to immunosuppressive therapy. PMID:25922588

  15. How should we measure function in patients with chronic heart and lung disease?

    PubMed

    Guyatt, G H; Thompson, P J; Berman, L B; Sullivan, M J; Townsend, M; Jones, N L; Pugsley, S O

    1985-01-01

    To elucidate the characteristics of measures of function in patients with chronic heart failure and chronic lung disease we administered four functional status questionnaires, a 6-min walk test and a cycle ergometer exercise test, to 43 patients limited in their day to day activities as a result of their underlying heart or lung disease. Correlations between these measures were calculated using Spearman's rank order correlation coefficient. The walk test correlated well with the cycle ergometer (r = 0.579), and almost as well with the four functional status questionnaires (r = 0.473-0.590) as the questionnaires did with one another (0.423-0.729). On the other hand, correlations between cycle ergometer results and the questionnaires was in each case 0.295 or lower, and none of these correlations reached statistical significance. These results suggest that exercise capacity in the laboratory can be differentiated from functional exercise capacity (the ability to undertake physically demanding activities of daily living) and that the walk test provides a good measure of function in patients with heart and lung disease.

  16. Lung function and respiratory symptoms among female hairdressers in Palestine: a 5-year prospective study

    PubMed Central

    Nemer, Maysaa; Kristensen, Petter; Nijem, Khaldoun; Bjertness, Espen; Skare, Øivind; Skogstad, Marit

    2015-01-01

    Objectives Hairdressers are exposed to chemicals at the workplace which are known to cause respiratory symptoms and asthma. This study aimed to examine changes in self-reported respiratory symptoms over 5 years, as well as to examine the lung function decline and determine whether it is within the expected range, to assess the dropout rate and reasons for leaving the profession, and to examine the associations between occupational factors and lung function changes at follow-up. Design Prospective study. Setting Female hairdressing salons in Hebron city, Palestine. Participants 170 female hairdressers who participated in a baseline survey in 2008 were followed up in 2013. A total of 161 participants participated in 2013. Outcome measures Change in reported respiratory symptoms and change in lung function over follow-up. Dropout from the profession and reasons for it. Differences between current and former hairdressers in respiratory symptoms and lung function at follow-up. Ambient air ammonia levels in 13 salons. Results Current hairdressers reported more respiratory symptoms in 2013 compared with baseline. Former hairdressers reported fewer symptoms at follow-up. At follow-up, current hairdressers showed a significant decrease in forced vital capacity of 35 mL/year (95% CI 26 to 44 mL/year) and of 31 mL/year (95% CI 25 to 36 mL/year) for forced expiratory volume in 1 s (FEV1). 28 (16%) of the hairdressers quit the job during the 5-year follow-up, 8 (28%) because of health problems. Hairdressers who had been working for 4 years or more at baseline showed a stronger decline in FEV1 compared with those who worked less than 4 years (difference 13, 95% CI 1 to 25). Conclusions Current hairdressers developed more respiratory symptoms and larger lung function decline than former hairdressers during follow-up. Few hairdressers left their profession because of respiratory health problems. Working for more years is associated with lung function decline among

  17. Early Changes in Clinical, Functional, and Laboratory Biomarkers in Workers at Risk of Indium Lung Disease

    PubMed Central

    Cummings, Kristin J.; Virji, M. Abbas; Trapnell, Bruce C.; Carey, Brenna; Healey, Terrance; Kreiss, Kathleen

    2015-01-01

    Rationale Occupational exposure to indium compounds, including indium–tin oxide, can result in potentially fatal indium lung disease. However, the early effects of exposure on the lungs are not well understood. Objectives To determine the relationship between short-term occupational exposures to indium compounds and the development of early lung abnormalities. Methods Among indium–tin oxide production and reclamation facility workers, we measured plasma indium, respiratory symptoms, pulmonary function, chest computed tomography, and serum biomarkers of lung disease. Relationships between plasma indium concentration and health outcome variables were evaluated using restricted cubic spline and linear regression models. Measurements and Main Results Eighty-seven (93%) of 94 indium–tin oxide facility workers (median tenure, 2 yr; median plasma indium, 1.0 μg/l) participated in the study. Spirometric abnormalities were not increased compared with the general population, and few subjects had radiographic evidence of alveolar proteinosis (n = 0), fibrosis (n = 2), or emphysema (n = 4). However, in internal comparisons, participants with plasma indium concentrations ≥1.0 μg/l had more dyspnea, lower mean FEV1 and FVC, and higher median serum Krebs von den Lungen-6 and surfactant protein-D levels. Spline regression demonstrated nonlinear exposure response, with significant differences occurring at plasma indium concentrations as low as 1.0 μg/l compared with the reference. Associations between health outcomes and the natural log of plasma indium concentration were evident in linear regression models. Associations were not explained by age, smoking status, facility tenure, or prior occupational exposures. Conclusions In indium–tin oxide facility workers with short-term, low-level exposure, plasma indium concentrations lower than previously reported were associated with lung symptoms, decreased spirometric parameters, and increased serum biomarkers of lung

  18. Accelerating self-consistent field convergence with the augmented Roothaan–Hall energy function

    PubMed Central

    Hu, Xiangqian; Yang, Weitao

    2010-01-01

    Based on Pulay’s direct inversion iterative subspace (DIIS) approach, we present a method to accelerate self-consistent field (SCF) convergence. In this method, the quadratic augmented Roothaan–Hall (ARH) energy function, proposed recently by Høst and co-workers [J. Chem. Phys. 129, 124106 (2008)], is used as the object of minimization for obtaining the linear coefficients of Fock matrices within DIIS. This differs from the traditional DIIS of Pulay, which uses an object function derived from the commutator of the density and Fock matrices. Our results show that the present algorithm, abbreviated ADIIS, is more robust and efficient than the energy-DIIS (EDIIS) approach. In particular, several examples demonstrate that the combination of ADIIS and DIIS (“ADIIS+DIIS”) is highly reliable and efficient in accelerating SCF convergence. PMID:20136307

  19. [The results of experimental study of six-hour heart-lung preservation by autoperfusion method--its evaluation of optimal conditions and lung function after preservation].

    PubMed

    Matsuoka, M; Makino, S; Hattori, R; Imura, M; Higashi, K; Morimoto, T; Yada, I; Namikawa, S; Yuasa, H; Kusagawa, M

    1989-04-01

    Up to date, it has been reported that the maintenance of ideal function of the preserved lungs were much more difficult than that of the hearts in heart-lung preservation. In this communication the authors have reported the results of experimental study for optimal conditions for preserving better function of the lungs by autoperfusion method by means of heart-lung preparation using 43 dogs. In this study the conditions of the preservation were fixed as following: perfusing blood temperature 29 degrees C, blood flow 30 ml/kg/min., FiO2 30%, FiCO2 5%, tidal volume 15 ml/kg, ventilation rate 10/min., and PEEP 5 cmH2O. Glucose-Insulin-Potassium (0.03 gm., 0.05 U., 0.02 mEq/kg/hr. respectively) were administered continuously by an infusion pump. The results showed that extravascular lung water contents after 6 hours of preservation was 0.79 (mean) +/- 0.01 (SD), which was increased only 1% over than the control group: 0.78 +/- 0.01. There was no significant difference of static lung compliance in two groups: the preserved group was 0.47 +/- 0.02 ml/gm.cmH2O compared to 0.51 +/- 0.06 in the control group. These results suggest that the autoperfusion method on our preserving conditions seems to be very promising and very effective to keep much better condition of the lungs in heart-lung preservation.

  20. Obesity and diabetes as accelerators of functional decline: can lifestyle interventions maintain functional status in high risk older adults?

    PubMed

    Anton, Stephen D; Karabetian, Christy; Naugle, Kelly; Buford, Thomas W

    2013-09-01

    Obesity and diabetes are known risk factors for the development of physical disability among older adults. With the number of seniors with these conditions rising worldwide, the prevention and treatment of physical disability in these persons have become a major public health challenge. Sarcopenia, the progressive loss of muscle mass and strength, has been identified as a common pathway associated with the initial onset and progression of physical disability among older adults. A growing body of evidence suggests that metabolic dysregulation associated with obesity and diabetes accelerates the progression of sarcopenia, and subsequently functional decline in older adults. The focus of this brief review is on the contributions of obesity and diabetes in accelerating sarcopenia and functional decline among older adults. We also briefly discuss the underexplored interaction between obesity and diabetes that may further accelerate sarcopenia and place obese older adults with diabetes at particularly high risk of disability. Finally, we review findings from studies that have specifically tested the efficacy of lifestyle-based interventions in maintaining the functional status of older persons with obesity and/or diabetes.

  1. Dust exposure, respiratory symptoms, and longitudinal decline of lung function in young coal miners.

    PubMed Central

    Carta, P; Aru, G; Barbieri, M T; Avataneo, G; Casula, D

    1996-01-01

    OBJECTIVES: To study the role of dust exposure on incidence of respiratory symptoms and decline of lung function in young coal miners. METHODS: The loss of lung function (forced vital capacity (FVC), forced expiratory volume in one second (FEV1), forced expiratory flow (MEF), carbon monoxide transfer factor (TLCO)) with time and the incidence of respiratory symptoms in 909 Sardinian coal miners (followed up between 1983 and 1993 with seven separate surveys) has been compared with the past and current individual exposures to respirable mixed coal dust. Multiple linear and logistic regression models were used simultaneously controlling for age, smoking, past occupational exposures, and other relevant covariates. RESULTS: According to the relatively low dust exposures experienced during the follow up few abnormal chest x ray films were detected. In the cross sectional analysis of initial data, significant associations between individual cumulative exposure to dust, decrements in FEV1 and MEFs, and increasing prevalence of respiratory symptoms were detected after allowing for the covariates included in the model. The yearly decline of FVC, FEV1, and single breath carbon monoxide transfer factor (TLCO/VA) was still significantly related to the individual exposure to dust experienced during the follow up, even after allowing for age, smoking, initial cumulative exposure to dust, and initial level of each functional variable. In logistic models, dust exposure was a significant predictor of the onset of respiratory symptoms besides age and smoking. CONCLUSIONS: The results show that even moderate exposures to mixed coal dust, as in our study, significantly affect lung function and incidence of symptoms of underground miners. Although the frequency of chest x ray examination might be fixed at every three or four years, yearly measurements of lung function (spirometry, MEFs, and TLCO) are recommended for evaluation of the respiratory risk from the coal mine environment to

  2. Variation in lung function is associated with worse clinical outcomes in cystic fibrosis

    PubMed Central

    Heinzmann-Filho, João Paulo; Pinto, Leonardo Araujo; Marostica, Paulo José Cauduro; Donadio, Márcio Vinícius Fagundes

    2015-01-01

    ABSTRACT OBJECTIVE: To determine whether the variation in lung function over one year is associated with worse clinical outcomes, as well as with a decline in lung function in the following years, in patients with cystic fibrosis (CF). METHODS: This was a retrospective study involving CF patients (4-19 years of age), evaluated over a three-year period. We evaluated demographic characteristics, chronic Pseudomonas aeruginosa infection, antibiotic use, hospitalization, six-minute walk distance (6MWD), and lung function. The inclusion criterion was having undergone pulmonary function testing at least three times in the first year and at least once in each of the next two years. RESULTS: We evaluated 35 CF patients. The variation in FEV1 in the first year (ΔFEV1) was greater among those who, in the third year, showed reduced FEV1, had a below-average 6MWD, or were hospitalized than among those with normal FEV1, normal 6MWD, or no hospital admissions, in that same year (p < 0.05), although no such difference was found for antibiotic use in the third year. Subjects showing a ΔFEV1 ≥ 10% also showed a greater decline in FEV1 over the two subsequent years (p = 0.04). The ΔFEV1 also showed an inverse correlation with absolute FEV1 in the third year (r = −0.340, p = 0.04) and with the rate of FEV1 decline (r = −0.52, p = 0.001). Linear regression identified ΔFEV1 as a predictor of FEV1 decline (coefficient of determination, 0.27). CONCLUSIONS: Significant variation in lung function over one year seems to be associated with a higher subsequent rate of FEV1 decline and worse clinical outcomes in CF patients. Short-term ΔFEV1 might prove useful as a predictor of CF progression in clinical practice. PMID:26785959

  3. Relation of fetal growth to adult lung function in south India

    PubMed Central

    Stein, C. E.; Kumaran, K.; Fall, C. H.; Shaheen, S. O.; Osmond, C.; Barker, D. J.

    1997-01-01

    BACKGROUND: Follow up studies in Britain have shown that low rates of fetal growth are followed by reduced lung function in adult life, independent of smoking and social class. It is suggested that fetal adaptations to undernutrition in utero result in permanent changes in lung structure, which in turn lead to chronic airflow obstruction. India has high rates of intrauterine growth retardation, but no study has examined the association between fetal growth and adult lung function in Indian people. We have related size at birth to lung function in an urban Indian population aged 38-59 years. METHODS: Two hundred and eighty six men and women born in one hospital in Mysore City, South India, during 1934-1953 were traced by a house-to-house survey of the city. Their mean forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) were measured using a turbine spirometer. These measurements were linked to their size at birth, recorded at the time. RESULTS: In both men and women mean FEV1 fell with decreasing birthweight. Adjusted for age and height, it fell by 0.09 litres with each pound (454 g) decrease in birthweight in men (95% confidence interval (CI) 0.01 to 0.16) and by 0.06 (95% CI -0.01 to 0.13) in women. Likewise, mean FVC fell by 0.11 litres (95% CI 0.02 to 0.19) with each pound decrease in birthweight in men, and by 0.08 litres (95% CI 0.002 to 0.16) in women. FEV1 and FVC were lower in men who smoked, but the associations with size at birth were independent of smoking. Small head circumference at birth was associated with a low FEV1/FVC ratio in men which may reflect restriction in airway growth in early gestation. CONCLUSION: This is further evidence that adult lung function is "programmed" in fetal life. Smoking may be particularly detrimental to the lung function of populations already disadvantaged by poor rates of fetal growth. 


 PMID:9404378

  4. The respiratory health and lung function of Anglo-American children in a smelter town

    SciTech Connect

    Dodge, R.

    1983-02-01

    Cooper smelters are large, usually isolated, sources of air pollution. Arizona has several such plants on the periphery of small communities. The smelters emit predominantly sulfur oxides and particulates, and the residents of these communities intermittently are exposed to high concentrations (24-h sulfur dioxide (SO2) . 250 to 500 micrograms/m3) of smelter smoke but little other pollution. This study compared the respiratory health of Anglo-American school children who lived in one smelter community with children living in another small community in Arizona that was free of smelter air pollution. The prevalence of cough, as determined by questionnaire, was 25.6% in the smelter town children and 14.3% in the nonsmelter town children (p less than 0.05). Pulmonary function at the study onset was equal in the two groups. Over the course of the 4 yr of study, lung function growth (measured as actual forced expiratory volume in one second (FEV1) after 4 yr of study minus predicted FEV1) was also equal in the smelter town and nonsmelter town children. These results suggest that children in smelter communities have slightly more cough when compared with children living in other communities, but no differences in initial lung function or lung function at yearly testing over the period of the study.

  5. Center of Mass Acceleration Feedback Control for Standing by Functional Neuromuscular Stimulation – a Simulation Study

    PubMed Central

    Audu, Musa L.; Kirsch, Robert F.; Triolo, Ronald J.

    2013-01-01

    The potential efficacy of total body center of mass (COM) acceleration for feedback control of standing balance by functional neuromuscular stimulation (FNS) following spinal cord injury (SCI) was investigated. COM acceleration may be a viable alternative to conventional joint kinematics due to its rapid responsiveness, focal representation of COM dynamics, and ease of measurement. A computational procedure was developed using an anatomically-realistic, three-dimensional, bipedal biomechanical model to determine optimal patterns of muscle excitations to produce targeted effects upon COM acceleration from erect stance. The procedure was verified with electromyographic data collected from standing able-bodied subjects undergoing systematic perturbations. Using 16 muscle groups targeted by existing implantable neuroprostheses, data were generated to train an artificial neural network (ANN)-based controller in simulation. During forward simulations, proportional feedback of COM acceleration drove the ANN to produce muscle excitation patterns countering the effects of applied perturbations. Feedback gains were optimized to minimize upper extremity (UE) loading required to stabilize against disturbances. Compared to the clinical case of maximum constant excitation, the controller reduced UE loading by 43% in resisting external perturbations and by 51% during simulated one-arm reaching. Future work includes performance assessment against expected measurement errors and developing user-specific control systems. PMID:22773529

  6. [Interpretation and use of routine pulmonary function tests: Spirometry, static lung volumes, lung diffusion, arterial blood gas, methacholine challenge test and 6-minute walk test].

    PubMed

    Bokov, P; Delclaux, C

    2016-02-01

    Resting pulmonary function tests (PFT) include the assessment of ventilatory capacity: spirometry (forced expiratory flows and mobilisable volumes) and static volume assessment, notably using body plethysmography. Spirometry allows the potential definition of obstructive defect, while static volume assessment allows the potential definition of restrictive defect (decrease in total lung capacity) and thoracic hyperinflation (increase in static volumes). It must be kept in mind that this evaluation is incomplete and that an assessment of ventilatory demand is often warranted, especially when facing dyspnoea: evaluation of arterial blood gas (searching for respiratory insufficiency) and measurement of the transfer coefficient of the lung, allowing with the measurement of alveolar volume to calculate the diffusing capacity of the lung for CO (DLCO: assessment of alveolar-capillary wall and capillary blood volume). All these pulmonary function tests have been the subject of an Americano-European Task force (standardisation of lung function testing) published in 2005, and translated in French in 2007. Interpretative strategies for lung function tests have been recommended, which define abnormal lung function tests using the 5th and 95th percentiles of predicted values (lower and upper limits of normal values). Thus, these recommendations need to be implemented in all pulmonary function test units. A methacholine challenge test will only be performed in the presence of an intermediate pre-test probability for asthma (diagnostic uncertainty), which is an infrequent setting. The most convenient exertional test is the 6-minute walk test that allows the assessment of walking performance, the search for arterial desaturation and the quantification of dyspnoea complaint.

  7. Measuring lung function using sound waves: role of the forced oscillation technique and impulse oscillometry system.

    PubMed

    Brashier, Bill; Salvi, Sundeep

    2015-03-01

    Measuring lung function is an important component in the decision making process for patients with obstructive airways disease (OAD). Not only does it help in arriving at a specific diagnosis, but it also helps in evaluating severity so that appropriate pharmacotherapy can be instituted, it helps determine prognosis and it helps evaluate response to therapy. Spirometry is currently the most commonly performed lung function test in clinical practice and is considered to be the gold standard diagnostic test for asthma and COPD. However, spirometry is not an easy test to perform because the forceful expiratory and inspiratory manoeuvres require good patient co-operation. Children aged <5 years, elderly people and those with physical and cognitive limitations cannot perform spirometry easily.

  8. Phase 2 Study of Accelerated Hypofractionated Thoracic Radiation Therapy and Concurrent Chemotherapy in Patients With Limited-Stage Small-Cell Lung Cancer

    SciTech Connect

    Xia, Bing; Hong, Ling-Zhi; Cai, Xu-Wei; Zhu, Zheng-Fei; Liu, Qi; Zhao, Kuai-Le; Fan, Min; Mao, Jing-Fang; Yang, Huan-Jun; Wu, Kai-Liang; Fu, Xiao-Long

    2015-03-01

    Purpose: To prospectively investigate the efficacy and toxicity of accelerated hypofractionated thoracic radiation therapy (HypoTRT) combined with concurrent chemotherapy in the treatment of limited-stage small-cell lung cancer (LS-SCLC), with the hypothesis that both high radiation dose and short radiation time are important in this setting. Methods and Materials: Patients with previously untreated LS-SCLC, Eastern Cooperative Oncology Group performance status of 0 to 2, and adequate organ function were eligible. HypoTRT of 55 Gy at 2.5 Gy per fraction over 30 days was given on the first day of the second or third cycle of chemotherapy. An etoposide/cisplatin regimen was given to 4 to 6 cycles. Patients who had a good response to initial treatment were offered prophylactic cranial irradiation. The primary endpoint was the 2-year progression-free survival rate. Results: Fifty-nine patients were enrolled from July 2007 through February 2012 (median age, 58 years; 86% male). The 2-year progression-free survival rate was 49.0% (95% confidence interval [CI] 35.3%-62.7%). Median survival time was 28.5 months (95% CI 9.0-48.0 months); the 2-year overall survival rate was 58.2% (95% CI 44.5%-71.9%). The 2-year local control rate was 76.4% (95% CI 63.7%-89.1%). The severe hematologic toxicities (grade 3 or 4) were leukopenia (32%), neutropenia (25%), and thrombocytopenia (15%). Acute esophagitis and pneumonitis of grade ≥3 occurred in 25% and 10% of the patients, respectively. Thirty-eight patients (64%) received prophylactic cranial irradiation. Conclusion: Our study showed that HypoTRT of 55 Gy at 2.5 Gy per fraction daily concurrently with etoposide/cisplatin chemotherapy has favorable survival and acceptable toxicity. This radiation schedule deserves further investigation in LS-SCLC.

  9. Divergent Functions of Toll-like Receptors during Bacterial Lung Infections

    PubMed Central

    Baral, Pankaj; Batra, Sanjay; Zemans, Rachel L.; Downey, Gregory P.

    2014-01-01

    Lower respiratory tract infections caused by bacteria are a major cause of death in humans irrespective of sex, race, or geography. Indeed, accumulated data indicate greater mortality and morbidity due to these infections than cancer, malaria, or HIV infection. Successful recognition of, followed by an appropriate response to, bacterial pathogens in the lungs is crucial for effective pulmonary host defense. Although the early recruitment and activation of neutrophils in the lungs is key in the response against invading microbial pathogens, other sentinels, such as alveolar macrophages, epithelial cells, dendritic cells, and CD4+ T cells, also contribute to the elimination of the bacterial burden. Pattern recognition receptors, such as Toll-like receptors (TLRs) and nucleotide-binding oligomerization domain–like receptors, are important for recognizing and responding to microbes during pulmonary infections. However, bacterial pathogens have acquired crafty evasive strategies to circumvent the pattern recognition receptor response and thus establish infection. Increased understanding of the function of TLRs and evasive mechanisms used by pathogens during pulmonary infection will deepen our knowledge of immunopathogenesis and is crucial for developing effective therapeutic and/or prophylactic measures. This review summarizes current knowledge of the multiple roles of TLRs in bacterial lung infections and highlights the mechanisms used by pathogens to modulate or interfere with TLR signaling in the lungs. PMID:25033332

  10. Divergent functions of Toll-like receptors during bacterial lung infections.

    PubMed

    Baral, Pankaj; Batra, Sanjay; Zemans, Rachel L; Downey, Gregory P; Jeyaseelan, Samithamby

    2014-10-01

    Lower respiratory tract infections caused by bacteria are a major cause of death in humans irrespective of sex, race, or geography. Indeed, accumulated data indicate greater mortality and morbidity due to these infections than cancer, malaria, or HIV infection. Successful recognition of, followed by an appropriate response to, bacterial pathogens in the lungs is crucial for effective pulmonary host defense. Although the early recruitment and activation of neutrophils in the lungs is key in the response against invading microbial pathogens, other sentinels, such as alveolar macrophages, epithelial cells, dendritic cells, and CD4(+) T cells, also contribute to the elimination of the bacterial burden. Pattern recognition receptors, such as Toll-like receptors (TLRs) and nucleotide-binding oligomerization domain-like receptors, are important for recognizing and responding to microbes during pulmonary infections. However, bacterial pathogens have acquired crafty evasive strategies to circumvent the pattern recognition receptor response and thus establish infection. Increased understanding of the function of TLRs and evasive mechanisms used by pathogens during pulmonary infection will deepen our knowledge of immunopathogenesis and is crucial for developing effective therapeutic and/or prophylactic measures. This review summarizes current knowledge of the multiple roles of TLRs in bacterial lung infections and highlights the mechanisms used by pathogens to modulate or interfere with TLR signaling in the lungs.

  11. Thoracic dust exposure is associated with lung function decline in cement production workers

    PubMed Central

    Notø, Hilde; Eduard, Wijnand; Skogstad, Marit; Fell, Anne Kristin; Thomassen, Yngvar; Skare, Øivind; Bergamaschi, Antonio; Pietroiusti, Antonio; Abderhalden, Rolf; Kongerud, Johny; Kjuus, Helge

    2016-01-01

    We hypothesised that exposure to workplace aerosols may lead to lung function impairment among cement production workers. Our study included 4966 workers in 24 cement production plants. Based on 6111 thoracic aerosol samples and information from questionnaires we estimated arithmetic mean exposure levels by plant and job type. Dynamic lung volumes were assessed by repeated spirometry testing during a mean follow-up time of 3.5 years (range 0.7–4.6 years). The outcomes considered were yearly change of dynamic lung volumes divided by the standing height squared or percentage of predicted values. Statistical modelling was performed using mixed model regression. Individual exposure was classified into quintile levels limited at 0.09, 0.89, 1.56, 2.25, 3.36, and 14.6 mg·m−3, using the lowest quintile as the reference. Employees that worked in administration were included as a second comparison group. Exposure was associated with a reduction in forced expiratory volume in 1 s (FEV1), forced expiratory volume in 6 s and forced vital capacity. For FEV1 % predicted a yearly excess decline of 0.84 percentage points was found in the highest exposure quintile compared with the lowest. Exposure at the higher levels found in this study may lead to a decline in dynamic lung volumes. Exposure reduction is therefore warranted. PMID:27103386

  12. Trajectories of Microbial Community Function in Response to Accelerated Remediation of Subsurface Metal Contaminants

    SciTech Connect

    Firestone, Mary

    2015-01-14

    Objectives of proposed research were to; Determine if the trajectories of microbial community composition and function following organic carbon amendment can be related to, and predicted by, key environmental determinants; Assess the relative importance of the characteristics of the indigenous microbial community, sediment, groundwater, and concentration of organic carbon amendment as the major determinants of microbial community functional response and bioremediation capacity; and Provide a fundamental understanding of the microbial community ecology underlying subsurface metal remediation requisite to successful application of accelerated remediation and long-term stewardship of DOE-IFC sites.

  13. Birth weight, childhood lower respiratory tract infection, and adult lung function

    PubMed Central

    Shaheen, S; Sterne, J; Tucker, J; Florey, C

    1998-01-01

    BACKGROUND—Historical cohort studies in England have found that impaired fetal growth and lower respiratory tract infections in early childhood are associated with lower levels of lung function in late adult life. These relations are investigated in a similar study in Scotland.
METHODS—In 1985-86 a follow up study was carried out of 1070 children who had been born in St Andrew's from 1921 to 1935 and followed from birth to 14 years of age by the Mackenzie Institute for Medical Research. Recorded information included birth weight and respiratory illnesses. The lung function of 239 of these individuals was measured.
RESULTS—There was no association between birth weight and lung function. Pneumonia before two years of age was associated with a difference in mean forced expiratory volume in one second (FEV1) of −0.39 litres (95% confidence interval (CI) −0.67, −0.11; p = 0.007) and in mean forced vital capacity (FVC) of −0.60 litres (95% CI −0.92, −0.28; p<0.001), after controlling for age, sex, height, smoking, type of spirometer, and other illnesses before two years. Similar reductions were seen in men and women. Bronchitis before two years was associated with smaller deficits in FEV1 and FVC. Asthma or wheeze at two years and older and cough after five years were also associated with a reduction in FEV1.
CONCLUSIONS—The relation between impaired fetal growth and lower lung function in late adult life seen in previous studies was not confirmed in this cohort. The deficits in FEV1 and FVC associated with pneumonia and bronchitis in the first two years of life are consistent with a causal relation.

 PMID:9797752

  14. Lung function changes in coke oven workers during 12 years of follow up

    PubMed Central

    Wu, J; Griffiths, D; Kreis, I; Darling, C

    2004-01-01

    Aims: To investigate the effect of exposure to coke oven emissions on the lung function of coke oven workers. Methods: The study population, followed from 1978 and 1990, was 580 male workers with at least two sets of lung function measurements (FVC, FEV1, FEV1/FVC, and FEF25–75%). An annual rate of change (time slope) for age and height adjusted lung function index was estimated for each subject. This "time slope" was then treated as the response variable in a weighted multiple regression analysis with selected predictors. Results: For all 580 subjects, each year of working in the "operation" group (the most exposed) was found to increase the FVC decline by around 0.7 ml/year (95% CI 0.1 to 1.3 ml/year). After the exclusion of 111 subjects without detailed work history, the above finding was confirmed and each year of exposure in "operation" was also found to increase the FEV1 decline by around 0.8 ml/year (95% CI 0.1 to 1.4 ml/year). Conclusions: These findings are consistent with the results of previous cross-sectional studies. Work duration in the most exposed position in the coke ovens was associated with increased annual decline for FVC and FEV1. The estimated effect of one year of work exposure in "operation" is equivalent, in terms of the reduction in lung function, to an estimated 2.1 pack-years of smoking for FVC and 1.2 pack-years of smoking for FEV1. PMID:15258275

  15. Associations between antioxidants and all-cause mortality among US adults with obstructive lung function

    PubMed Central

    Ford, Earl S.; Li, Chaoyang; Cunningham, Timothy J.; Croft, Janet B.

    2015-01-01

    Chronic obstructive pulmonary disease is characterised by oxidative stress, but little is known about the associations between antioxidant status and all-cause mortality in adults with this disease. The objective of the present study was to examine the prospective associations between concentrations of α- and β-carotene, β-cryptoxanthin, lutein/zeaxanthin, lycopene, Se, vitamin C and α-tocopherol and all-cause mortality among US adults with obstructive lung function. Data collected from 1492 adults aged 20–79 years with obstructive lung function in the National Health and Nutrition Examination Survey III (1988–94) were used. Through 2006, 629 deaths were identified during a median follow-up period of 14 years. After adjustment for demographic variables, the concentrations of the following antioxidants modelled as continuous variables were found to be inversely associated with all-cause mortality among adults with obstructive lung function: α-carotene (P=0.037); β-carotene (P=0.022); cryptoxanthin (P=0.022); lutein/zeaxanthin (P=0.004); total carotenoids (P=0.001); vitamin C (P<0.001). In maximally adjusted models, only the concentrations of lycopene (P=0.013) and vitamin C (P=0.046) were found to be significantly and inversely associated with all-cause mortality. No effect modification by sex was detected, but the association between lutein/zeaxanthin concentrations and all-cause mortality varied by smoking status (Pinteraction = 0.048). The concentrations of lycopene and vitamin C were inversely associated with all-cause mortality in this cohort of adults with obstructive lung function. PMID:25315508

  16. CDH13 gene-by-PM10 interaction effect on lung function decline in Korean men.

    PubMed

    Kim, Hyun-Jin; Min, Jin-Young; Min, Kyoung-Bok; Seo, Yong-Seok; Sung, Joohon; Yun, Jae Moon; Kwon, Hyuktae; Cho, Belong; Park, Jin-Ho; Kim, Jong-Il

    2017-02-01

    Lung function can be influenced by genetic factors, which may explain individual differences in susceptibility to the effects of air pollution. This study investigated whether the effect of particulate matter with an aerodynamic diameter ≤10 μm (PM10) on lung function is modified by Cadherin 13 (CDH13) genetic variants in Korean men. This study included a total of 1827 men who were recruited from two health check-up centers, and the annual average PM10 concentrations were used. A total of 200 single-nucleotide polymorphisms (SNPs) of the CDH13 gene were selected for this study. We found that a SNP in CHD13 intron, rs1862830, had the strongest associations with both forced expiratory volume in 1 s (FEV1) (pint = 1.90 × 10(-4)) and forced vital capacity (FVC) (pint = 1.88 × 10(-3)) by interacting with PM10 in a recessive model. A stratified association analysis according to this SNP showed that PM10 in the AG or GG genotype group was not significantly associated with either FEV1 or FVC, whereas in homozygous risk-allele carriers (AA), FEV1 and FVC decreased significantly (by 3.8% and 3.1%, respectively) per 10 μg/m(3) of increase in PM10 concentration. This pattern was also reproducible in the independent subgroups that were classified according to recruitment site. The present study replicated the CDH13 gene-by-PM10 interaction effect on lung function at the gene level, revealing that a genetic variant of CDH13 modified the relationship between PM10 and lung function decline in Korean men.

  17. Relationship between exhaled NO, respiratory symptoms, lung function, bronchial hyperresponsiveness, and blood eosinophilia in school children

    PubMed Central

    Steerenberg, P; Janssen, N; de Meer, G; Fischer, P; Nierkens, S; van Loveren, H; Opperhuizen, A; Brunekreef, B; van Amsterdam, J G C

    2003-01-01

    Methods: Levels of eNO in a sample of 450 children aged 7–12 years out of a total sample of 2504 school children living in different urban areas near motorways were determined. The aim of this cross-sectional study was to explore the relationship between eNO, impairment of lung function (PEF, FVC, FEV1 and MMEF), bronchial hyperresponsiveness (BHR), and blood eosinophilia in children with and without atopy as assessed by skin prick testing. Results: Regression analysis showed that wheezing and nasal discharge and conjunctivitis that had occurred during the previous 12 months were positively associated with eNO levels in atopic children (relative increase of 1.48 and 1.41, respectively; p<0.05) but not in non-atopic children. Similarly, BHR and the number of blood eosinophils per ml were positively associated with eNO levels in atopic children (relative increase of 1.55 and 2.29, respectively; p<0.05) but not in non-atopic children. The lung function indices PEF, FVC, FEV1 and MMEF were not associated with eNO levels. Conclusions: In addition to conventional lung function tests and symptom questionnaires, eNO is a suitable measure of airway inflammation and its application may reinforce the power of epidemiological surveys on respiratory health. PMID:12612304

  18. Preclinical anatomical, molecular, and functional imaging of the lung with multiple modalities.

    PubMed

    Gammon, Seth T; Foje, Nathan; Brewer, Elizabeth M; Owers, Elizabeth; Downs, Charles A; Budde, Matthew D; Leevy, W Matthew; Helms, My N

    2014-05-15

    In vivo imaging is an important tool for preclinical studies of lung function and disease. The widespread availability of multimodal animal imaging systems and the rapid rate of diagnostic contrast agent development have empowered researchers to noninvasively study lung function and pulmonary disorders. Investigators can identify, track, and quantify biological processes over time. In this review, we highlight the fundamental principles of bioluminescence, fluorescence, planar X-ray, X-ray computed tomography, magnetic resonance imaging, and nuclear imaging modalities (such as positron emission tomography and single photon emission computed tomography) that have been successfully employed for the study of lung function and pulmonary disorders in a preclinical setting. The major principles, benefits, and applications of each imaging modality and technology are reviewed. Limitations and the future prospective of multimodal imaging in pulmonary physiology are also discussed. In vivo imaging bridges molecular biological studies, drug design and discovery, and the imaging field with modern medical practice, and, as such, will continue to be a mainstay in biomedical research.

  19. Association of Lung Function, Chest Radiographs and Clinical Features in Infants with Cystic Fibrosis

    PubMed Central

    Rosenfeld, Margaret; Farrell, Philip M.; Kloster, Margaret; Swanson, Jonathan O.; Vu, Thuy; Brumback, Lyndia; Acton, James D.; Castile, Robert G.; Colin, Andrew A.; Conrad, Carol K.; Hart, Meeghan A.; Kerby, Gwendolyn S.; Hiatt, Peter W.; Mogayzel, Peter J.; Johnson, Robin C.; Davis, Stephanie D.

    2013-01-01

    Background The optimal strategy for monitoring cystic fibrosis (CF) lung disease in infancy remains unclear. Objective To describe longitudinal associations between infant pulmonary function tests (iPFTs), chest radiograph (CXR) scores and other characteristics. Methods CF patients ≤ 24 months old were enrolled in a 10-center study evaluating iPFTs 4 times over a year. CXRs ~1 year apart were scored with the Wisconsin and Brasfield systems. Associations of iPFT parameters with clinical characteristics were evaluated with mixed effects models. Results The 100 participants contributed 246 acceptable flow/volume (FEV0.5, FEF75) and 303 acceptable functional residual capacity (FRC) measurements and 171 CXRs. Both Brasfield and Wisconsin CXR scores worsened significantly over the 1 year interval. Worse Wisconsin CXR scores and S. aureus were both associated with hyperinflation (significantly increased FRC) but not with diminished FEV0.5 or FEF75. Parent-reported cough was associated with significantly diminished FEF75 but not with hyperinflation. Conclusions In this infant cohort in whom we previously reported worsening in average lung function, CXR scores also worsened over a year. The significant associations detected between both Wisconsin CXR score and S. aureus and hyperinflation, as well as between cough and diminished flows, reinforce the ability of iPFTs and CXRs to detect early CF lung disease. PMID:23722613

  20. Lung Function, Airway Inflammation, and Polycyclic Aromatic Hydrocarbons Exposure in Mexican Schoolchildren

    PubMed Central

    Barraza-Villarreal, Albino; Escamilla-Nuñez, Maria Consuelo; Schilmann, Astrid; Hernandez-Cadena, Leticia; Li, Zheng; Romanoff, Lovisa; Sjödin, Andreas; Del Río-Navarro, Blanca Estela; Díaz-Sanchez, David; Díaz-Barriga, Fernando; Sly, Peter; Romieu, Isabelle

    2015-01-01

    Objective To determine the association of exposure to polycyclic aromatic hydrocarbons (PAHs) with lung function and pH of exhaled breath condensate (EBC) in Mexican schoolchildren. Methods A pilot study was performed in a subsample of 64 schoolchildren from Mexico City. Lung function and pH of EBC were measured and metabolites of PAHs in urine samples were determined. The association was analyzed using robust regression models. Results A 10% increase in the concentrations of 2-hydroxyfluorene was significantly negatively associated with forced expiratory volume in 1 second (−11.2 mL, 95% CI: −22.2 to −0.02), forced vital capacity (−11.6 mL, 95% CI: −22.9 to −0.2), and pH of EBC (−0.035, 95% CI: −0.066 to −0.005). Conclusion Biomarkers of PAHs exposure were inversely associated with lung function and decrease of ph of EBC as a marker of airway inflammation in Mexican schoolchildren. PMID:24500378

  1. Western red cedar dust exposure and lung function: a dose-response relationship.

    PubMed

    Noertjojo, H K; Dimich-Ward, H; Peelen, S; Dittrick, M; Kennedy, S M; Chan-Yeung, M

    1996-10-01

    The relationship between levels of cumulative red cedar dust exposure and decline in lung function was explored in an 11-yr follow-up study of 243 sawmill workers who participated in at least two occasions. We also studied 140 office workers in a similar manner as control subjects. Workers with asthma were excluded from the analysis. During the period of the study, 916 personal and 216 area samples of dust were collected from the sawmill. Cumulative wood dust exposure was calculated for each sawmill worker according to the duration and exposure in each job, based on the geometric mean of all dust measurements for that job. Average daily dust exposure was calculated by dividing the total cumulative exposure by the number of days of work. Workers were divided into low-, medium-, and high-exposure groups with mean daily level of exposure of < 0.2, 0.2 to 0.4, and > 0.4 mg/m3, respectively. Sawmill workers had significantly greater declines in FEV1 and FVC compared with office workers adjusted for age, smoking, and initial lung function. A dose-response relationship was observed between the level of exposure and the annual decline in FVC. We conclude that exposure to Western red cedar dust is associated with a greater decline in lung function which may lead to development of chronic airflow limitation.

  2. X-ray findings, lung function, and respiratory symptoms in black South African vermiculite workers

    SciTech Connect

    Hessel, P.A.; Sluis-Cremer, G.K.

    1989-01-01

    Health effects have been documented among American vermiculite workers who mined and processed vermiculite contaminated with amphibole asbestos, viz., tremolite-actinolite. Workers mining and processing South Africa vermiculite (N = 172), which contains very little asbestos, underwent x-ray examination and lung function testing and completed a respiratory symptom questionnaire. The vermiculite workers were compared with other workers involved in the mining or refining of copper. Only two of the vermiculite workers showed evidence of small opacities of 1/0 or more (according to the ILO 1980 classification); lung function was comparable with the other groups of workers, and there was no excess of respiratory symptoms among the vermiculite workers. It is concluded that workers exposed to vermiculite that is minimally contaminated with asbestos are probably not at risk for pneumoconiosis, lung function impairment, or respiratory symptoms. It is likely that the health effects observed in other studies of vermiculite workers are the result of concomitant asbestos exposure. A risk of mesothelioma caused by the fiber content of the vermiculite cannot be excluded by this study.

  3. The influence of lung function on exercise capacity in patients with type 2 diabetes.

    PubMed

    Kitahara, Yoshihiro; Hattori, Noboru; Yokoyama, Akihito; Yamane, Kiminori; Sekikawa, Kiyokazu; Inamizu, Tsutomu; Kohno, Nobuoki

    2010-03-01

    Patients with type 2 diabetes have impaired exercise capacity. While numerous factors are known to contribute to impaired exercise capacity, the role of lung function remains unclear. We conducted the present study to investigate the influence of lung function on exercise capacity in patients with type 2 diabetes. Cardiopulmonary exercise testing was carried out in 31 male patients with type 2 diabetes without diabetic complications or cardiopulmonary diseases. Patients with abnormal spirometry results such as a percentage of predicted forced vital capacity (%FVC) < 80% and/or a ratio of forced expiratory volume in one second (FEV1) to FVC (FEV1/FVC) < 70% were excluded from the study. We used the percentage of predicted maximal oxygen uptake (%VO2max) as an index of exercise capacity. The correlations between %VO2max and lung function and other factors known to be associated with impaired exercise capacity were then assessed. Univariate analysis revealed %VO2max correlated significantly with percentage of predicted FEV1 (%FEV1), duration of type 2 diabetes, regular exercise habits, and systolic and diastolic blood pressures. In a multivariate analysis, %FEV1 and regular exercise habits were found to be independent determinants of %VO2max. A mild reduction in %FEV1, which may be a complication of diabetes, is associated with impaired exercise capacity in patients with type 2 diabetes. When evaluating spirometric values in patients with type 2 diabetes, a reduction in %FEV1 should be noted even when both %FVC and FEV1/FVC are within normal limits.

  4. Discrepancies between lung function and asthma control: asthma perception and association with demographics and anxiety.

    PubMed

    Steele, Ashton M; Meuret, Alicia E; Millard, Mark W; Ritz, Thomas

    2012-01-01

    Understanding asthma symptom perception is necessary for reducing unnecessary costs both for asthma sufferers and society and will contribute to improving asthma management. The primary aim of this study was to develop and test a standardized method for classification of asthma perceiver categories into under-, normal, and overperceiver groups based on the comparison between self-report and lung function components of asthma control. Additionally, the degree to which demographic variables and anxiety contributed to the classification of patients into perceiver groups was examined. Patients underwent methacholine or reversibility testing to confirm asthma diagnosis. Next, participants completed lung function testing over 3 days before their next appointment. Finally, patients filled out demographic and self-report measures including the Asthma Control Test (ACT). Each self-report category of control assessed by the ACT (interference, shortness of breath, nighttime awakenings, rescue inhaler usage, and a composite total score) was compared with lung function measurements using a modified version of the asthma risk grid. Using the modified asthma risk grid to determine perceiver categorization, this sample included 14 underperceivers, 29 normal perceivers, and 36 overperceivers. A discriminant analysis was performed that indicated that a majority of underperceivers were characterized by being African American and having low asthma-specific anxiety. Normal perceivers in this sample tended to be older. Overperceivers tended to be female. Our findings encourage further research using the reported method of classifying asthma patients into perceiver categories.

  5. Changes in lung function after working with the shotcrete lining method under compressed air conditions.

    PubMed Central

    Kessel, R; Redl, M; Mauermayer, R; Praml, G J

    1989-01-01

    Shotcrete techniques under compressed air are increasingly applied in the construction of tunnels. Up to now little is known about the influence of shotcrete dusts on the function of the lung. The lung function of 30 miners working with shotcrete under compressed air (before and after one shift) was measured. They carried personal air samplers to assess the total dust exposure. Long term effects were studied on a second group of 29 individuals exposed to shotcrete dusts and compressed air for two years. A significant increase of airway resistance and a significant decrease of some flow-volume parameters were found after one workshift. These changes partially correlate close to the dust exposure. After two years exposure a significant decrease of mean expiratory flow (MEF)50 and MEF25 was found. These results point to damage in the small airways and emphasise the major role of the lung function test--including the flow-volume manoeuvre for the medical examination of the workers. Additionally, they should carry filter masks. Images PMID:2923823

  6. Changes in lung function after working with the shotcrete lining method under compressed air conditions.

    PubMed

    Kessel, R; Redl, M; Mauermayer, R; Praml, G J

    1989-02-01

    Shotcrete techniques under compressed air are increasingly applied in the construction of tunnels. Up to now little is known about the influence of shotcrete dusts on the function of the lung. The lung function of 30 miners working with shotcrete under compressed air (before and after one shift) was measured. They carried personal air samplers to assess the total dust exposure. Long term effects were studied on a second group of 29 individuals exposed to shotcrete dusts and compressed air for two years. A significant increase of airway resistance and a significant decrease of some flow-volume parameters were found after one workshift. These changes partially correlate close to the dust exposure. After two years exposure a significant decrease of mean expiratory flow (MEF)50 and MEF25 was found. These results point to damage in the small airways and emphasise the major role of the lung function test--including the flow-volume manoeuvre for the medical examination of the workers. Additionally, they should carry filter masks.

  7. Air Pollution–Associated Changes in Lung Function among Asthmatic Children in Detroit

    PubMed Central

    Lewis, Toby C.; Robins, Thomas G.; Dvonch, J. Timothy; Keeler, Gerald J.; Yip, Fuyuen Y.; Mentz, Graciela B.; Lin, Xihong; Parker, Edith A.; Israel, Barbara A.; Gonzalez, Linda; Hill, Yolanda

    2005-01-01

    In a longitudinal cohort study of primary-school–age children with asthma in Detroit, Michigan, we examined relationships between lung function and ambient levels of particulate matter ≤ 10 μm and ≤ 2.5 μm in diameter (PM10 and PM2.5) and ozone at varying lag intervals using generalized estimating equations. Models considered effect modification by maintenance corticosteroid (CS) use and by the presence of an upper respiratory infection (URI) as recorded in a daily diary among 86 children who participated in six 2-week seasonal assessments from winter 2001 through spring 2002. Participants were predominantly African American from families with low income, and > 75% were categorized as having persistent asthma. In both single-pollutant and two-pollutant models, many regressions demonstrated associations between higher exposure to ambient pollutants and poorer lung function (increased diurnal variability and decreased lowest daily values for forced expiratory volume in 1 sec) among children using CSs but not among those not using CSs, and among children reporting URI symptoms but not among those who did not report URIs. Our findings suggest that levels of air pollutants in Detroit, which are above the current National Ambient Air Quality Standards, adversely affect lung function of susceptible asthmatic children. PMID:16079081

  8. COPD Patients with Exertional Desaturation Are at a Higher Risk of Rapid Decline in Lung Function

    PubMed Central

    Kim, Changhwan; Park, Yong Bum; Park, So Young; Park, Sunghoon; Kim, Cheol-Hong; Park, Sang Myeon; Lee, Myung-Goo; Hyun, In-Gyu; Jung, Ki-Suck

    2014-01-01

    Purpose A recent study demonstrated that exertional desaturation is a predictor of rapid decline in lung function in patients with chronic obstructive pulmonary disease (COPD); however, the study was limited by its method used to detect exertional desaturation. The main purpose of this study was to explore whether exertional desaturation assessed using nadir oxygen saturation (SpO2) during the 6-minute walk test (6MWT) can predict rapid lung function decline in patients with COPD. Materials and Methods A retrospective analysis was performed on 57 patients with moderate to very severe COPD who underwent the 6MWT. Exertional desaturation was defined as a nadir SpO2 of <90% during the 6MWT. Rapid decline was defined as an annual rate of decline in forced expiratory volume in 1 second (FEV1) ≥50 mL. Patients were divided into rapid decliner (n=26) and non-rapid decliner (n=31) groups. Results A statistically significant difference in exertional desaturation was observed between rapid decliners and non-rapid decliners (17 vs. 8, p=0.003). No differences were found between the groups for age, smoking status, BODE index, and FEV1. Multivariate analysis showed that exertional desaturation was a significant independent predictor of rapid decline in patients with COPD (relative risk, 6.8; 95% CI, 1.8 to 25.4; p=0.004). Conclusion This study supports that exertional desaturation is a predictor of rapid lung function decline in male patients with COPD. PMID:24719141

  9. Obesity-induced oxidative stress, accelerated functional decline with age and increased mortality in mice

    PubMed Central

    Zhang, Yiqiang; Fischer, Kathleen E.; Soto, Vanessa; Liu, Yuhong; Sosnowska, Danuta; Richardson, Arlan; Salmon, Adam B.

    2015-01-01

    Obesity is a serious chronic disease that increases the risk of numerous co-morbidities including metabolic syndrome, cardiovascular disease and cancer as well as increases risk of mortality leading some to suggest this represents accelerated aging. Obesity is associated with significant increases in oxidative stress in vivo and, despite the well-explored relationship between oxidative stress and aging, the role this plays in the increased mortality of obese subjects remains an unanswered question. Here, we addressed this by undertaking a comprehensive, longitudinal study of a group of high fat-fed obese mice and assessed both their changes in oxidative stress and in their performance in physiological assays known to decline with aging. In female C57BL/6J mice fed a high-fat diet starting in adulthood, mortality was significantly increased in high fat-fed mice as was oxidative damage in vivo. High fat-feeding significantly accelerated the decline in performance in several assays, including activity, gait, and rotarod. However, we also found that obesity had little effect on other markers and actually improved performance in grip strength, a marker of muscular function. Together, this first comprehensive assessment of longitudinal functional changes in high fat-fed mice suggests that obesity may induce segmental acceleration of some of the aging process. PMID:25558793

  10. Correction of dispersion and the betatron functions in the CEBAF accelerator

    SciTech Connect

    Lebedev, V.A.; Bickley, M.; Schaffner, S.; Zeijts, J. van; Krafft, G.A.; Watson, C.

    1996-10-01

    During the commissioning of the CEBAF accelerator, correction of dispersion and momentum compaction, and, to a lesser extent, transverse transfer matrices were essential for robust operation. With changing machine conditions, repeated correction was found necessary. To speed the diagnostic process the authors developed a method which allows one to rapidly track the machine optics. The method is based on measuring the propagation of 30 Hz modulated betatron oscillations downstream of a point of perturbation. Compared to the usual methods of dispersion or difference orbit measurement, synchronous detection of the beam displacement, as measured by beam position monitors, offers significantly improved speed and accuracy of the measurements. The beam optics of the accelerator was altered to decrease lattice sensitivity at critical points and to simplify control of the betatron function match. The calculation of the Courant-Snyder invariant from signals of each pair of nearby beam position monitors has allowed one to perform on-line measurement and correction of the lattice properties.

  11. Leptin Matures Aspects of Lung Structure and Function in the Ovine Fetus.

    PubMed

    De Blasio, Miles J; Boije, Maria; Kempster, Sarah L; Smith, Gordon C S; Charnock-Jones, D Stephen; Denyer, Alice; Hughes, Alexandra; Wooding, F B Peter; Blache, Dominique; Fowden, Abigail L; Forhead, Alison J

    2016-01-01

    In human and ovine fetuses, glucocorticoids stimulate leptin secretion, although the extent to which leptin mediates the maturational effects of glucocorticoids on pulmonary development is unclear. This study investigated the effects of leptin administration on indices of lung structure and function before birth. Chronically catheterized singleton sheep fetuses were infused iv for 5 days with either saline or recombinant ovine leptin (0.5 mg/kg · d leptin (LEP), 0.5 LEP or 1.0 mg/kg · d, 1.0 LEP) from 125 days of gestation (term ∼145 d). Over the infusion, leptin administration increased plasma leptin, but not cortisol, concentrations. On the fifth day of infusion, 0.5 LEP reduced alveolar wall thickness and increased the volume at closing pressure of the pressure-volume deflation curve, interalveolar septal elastin content, secondary septal crest density, and the mRNA abundance of the leptin receptor (Ob-R) and surfactant protein (SP) B. Neither treatment influenced static lung compliance, maximal lung volume at 40 cmH2O, lung compartment volumes, alveolar surface area, pulmonary glycogen, protein content of the long form signaling Ob-Rb or phosphorylated signal transducers and activators of transcription-3, or mRNA levels of SP-A, C, or D, elastin, vascular endothelial growth factor-A, the vascular endothelial growth factor receptor 2, angiotensin-converting enzyme, peroxisome proliferator-activated receptor γ, or parathyroid hormone-related peptide. Leptin administration in the ovine fetus during late gestation promotes aspects of lung maturation, including up-regulation of SP-B.

  12. Targeted Type 2 Alveolar Cell Depletion. A Dynamic Functional Model for Lung Injury Repair

    PubMed Central

    Garcia, Orquidea; Hiatt, Michael J.; Lundin, Amber; Lee, Jooeun; Reddy, Raghava; Navarro, Sonia; Kikuchi, Alex

    2016-01-01

    Type 2 alveolar epithelial cells (AEC2) are regarded as the progenitor population of the alveolus responsible for injury repair and homeostatic maintenance. Depletion of this population is hypothesized to underlie various lung pathologies. Current models of lung injury rely on either uncontrolled, nonspecific destruction of alveolar epithelia or on targeted, nontitratable levels of fixed AEC2 ablation. We hypothesized that discrete levels of AEC2 ablation would trigger stereotypical and informative patterns of repair. To this end, we created a transgenic mouse model in which the surfactant protein-C promoter drives expression of a mutant SR39TK herpes simplex virus-1 thymidine kinase specifically in AEC2. Because of the sensitivity of SR39TK, low doses of ganciclovir can be administered to these animals to induce dose-dependent AEC2 depletion ranging from mild (50%) to lethal (82%) levels. We demonstrate that specific levels of AEC2 depletion cause altered expression patterns of apoptosis and repair proteins in surviving AEC2 as well as distinct changes in distal lung morphology, pulmonary function, collagen deposition, and expression of remodeling proteins in whole lung that persist for up to 60 days. We believe SPCTK mice demonstrate the utility of cell-specific expression of the SR39TK transgene for exerting fine control of target cell depletion. Our data demonstrate, for the first time, that specific levels of type 2 alveolar epithelial cell depletion produce characteristic injury repair outcomes. Most importantly, use of these mice will contribute to a better understanding of the role of AEC2 in the initiation of, and response to, lung injury. PMID:26203800

  13. Poor Baseline Pulmonary Function May Not Increase the Risk of Radiation-Induced Lung Toxicity

    SciTech Connect

    Wang, Jingbo; Cao, Jianzhong; Yuan, Shuanghu; Arenberg, Douglas; Stanton, Paul; Tatro, Daniel; Ten Haken, Randall K.; Kong, Feng-Ming

    2013-03-01

    Purpose: Poor pulmonary function (PF) is often considered a contraindication to definitive radiation therapy for lung cancer. This study investigated whether baseline PF was associated with radiation-induced lung toxicity (RILT) in patients with non-small cell lung cancer (NSCLC) receiving conformal radiation therapy (CRT). Methods and Materials: NSCLC patients treated with CRT and tested for PF at baseline were eligible. Baseline predicted values of forced expiratory volume in 1 sec (FEV1), forced vital capacity (FVC), and diffusion capacity of lung for carbon monoxide (DLCO) were analyzed. Additional factors included age, gender, smoking status, Karnofsky performance status, coexisting chronic obstructive pulmonary disease (COPD), tumor location, histology, concurrent chemotherapy, radiation dose, and mean lung dose (MLD) were evaluated for RILT. The primary endpoint was symptomatic RILT (SRILT), including grade ≥2 radiation pneumonitis and fibrosis. Results: There was a total of 260 patients, and SRILT occurred in 58 (22.3%) of them. Mean FEV1 values for SRILT and non-SRILT patients were 71.7% and 65.9% (P=.077). Under univariate analysis, risk of SRILT increased with MLD (P=.008), the absence of COPD (P=.047), and FEV1 (P=.077). Age (65 split) and MLD were significantly associated with SRILT in multivariate analysis. The addition of FEV1 and age with the MLD-based model slightly improved the predictability of SRILT (area under curve from 0.63-0.70, P=.088). Conclusions: Poor baseline PF does not increase the risk of SRILT, and combining FEV1, age, and MLD may improve the predictive ability.

  14. Individualized prediction of lung-function decline in chronic obstructive pulmonary disease

    PubMed Central

    Zafari, Zafar; Sin, Don D.; Postma, Dirkje S.; Löfdahl, Claes-Göran; Vonk, Judith; Bryan, Stirling; Lam, Stephen; Tammemagi, C. Martin; Khakban, Rahman; Man, S.F. Paul; Tashkin, Donald; Wise, Robert A.; Connett, John E.; McManus, Bruce; Ng, Raymond; Hollander, Zsuszanna; Sadatsafavi, Mohsen

    2016-01-01

    Background: The rate of lung-function decline in chronic obstructive pulmonary disease (COPD) varies substantially among individuals. We sought to develop and validate an individualized prediction model for forced expiratory volume at 1 second (FEV1) in current smokers with mild-to-moderate COPD. Methods: Using data from a large long-term clinical trial (the Lung Health Study), we derived mixed-effects regression models to predict future FEV1 values over 11 years according to clinical traits. We modelled heterogeneity by allowing regression coefficients to vary across individuals. Two independent cohorts with COPD were used for validating the equations. Results: We used data from 5594 patients (mean age 48.4 yr, 63% men, mean baseline FEV1 2.75 L) to create the individualized prediction equations. There was significant between-individual variability in the rate of FEV1 decline, with the interval for the annual rate of decline that contained 95% of individuals being −124 to −15 mL/yr for smokers and −83 to 15 mL/yr for sustained quitters. Clinical variables in the final model explained 88% of variation around follow-up FEV1. The C statistic for predicting severity grades was 0.90. Prediction equations performed robustly in the 2 external data sets. Interpretation: A substantial part of individual variation in FEV1 decline can be explained by easily measured clinical variables. The model developed in this work can be used for prediction of future lung health in patients with mild-to-moderate COPD. Trial registration: Lung Health Study — ClinicalTrials.gov, no. NCT00000568; Pan-Canadian Early Detection of Lung Cancer Study — ClinicalTrials.gov, no. NCT00751660 PMID:27486205

  15. Continued artificial selection for running endurance in rats is associated with improved lung function.

    PubMed

    Kirkton, Scott D; Howlett, Richard A; Gonzalez, Norberto C; Giuliano, Patrick G; Britton, Steven L; Koch, Lauren G; Wagner, Harrieth E; Wagner, Peter D

    2009-06-01

    Previous studies found that selection for endurance running in untrained rats produced distinct high (HCR) and low (LCR) capacity runners. Furthermore, despite weighing 14% less, 7th generation HCR rats achieved the same absolute maximal oxygen consumption (Vo(2max)) as LCR due to muscle adaptations that improved oxygen extraction and use. However, there were no differences in cardiopulmonary function after seven generations of selection. If selection for increased endurance capacity continued, we hypothesized that due to the serial nature of oxygen delivery enhanced cardiopulmonary function would be required. In the present study, generation 15 rats selected for high and low endurance running capacity showed differences in pulmonary function. HCR, now 25% lighter than LCR, reached a 12% higher absolute Vo(2max) than LCR, P < 0.05 (49% higher Vo(2max)/kg). Despite the 25% difference in body size, both lung volume (at 20 cmH(2)O airway pressure) and exercise diffusing capacity were similar in HCR and LCR. Lung volume of LCR lay on published mammalian allometrical relationships while that of HCR lay above that line. Alveolar ventilation at Vo(2max) was 30% higher, P < 0.05 (78% higher, per kg), arterial Pco(2) was 4.5 mmHg (17%) lower, P < 0.05, while total pulmonary vascular resistance was (insignificantly) 5% lower (30% lower, per kg) in HCR. The smaller mass of HCR animals was due mostly to a smaller body frame rather than to a lower fat mass. These findings show that by generation 15, lung size in smaller HCR rats is not reduced in concert with their smaller body size, but has remained similar to that of LCR, supporting the hypothesis that continued selection for increased endurance capacity requires relatively larger lungs, supporting greater ventilation, gas exchange, and pulmonary vascular conductance.

  16. Calf Lung Surfactant Recovers Surface Functionality After Exposure to Aerosols Containing Polymeric Particles

    PubMed Central

    Farnoud, Amir M.

    2016-01-01

    Abstract Background: Recent studies have shown that colloidal particles can disrupt the interfacial properties of lung surfactant and thus key functional abilities of lung surfactant. However, the mechanisms underlying the interactions between aerosols and surfactant films remain poorly understood, as our ability to expose films to particles via the aerosol route has been limited. The aim of this study was to develop a method to reproducibly apply aerosols with a quantifiable particle dose on lung surfactant films and investigate particle-induced changes to the interfacial properties of the surfactant under conditions that more closely mimic those in vivo. Methods: Films of DPPC and Infasurf® were exposed to aerosols containing polystyrene particles generated using a Dry Powder Insufflator™. The dose of particles deposited on surfactant films was determined via light absorbance. The interfacial properties of the surfactant were studied using a Langmuir-Wilhelmy balance during surfactant compression to film collapse and cycles of surface compression and expansion at a fast cycling rate within a small surface area range. Results: Exposure of surfactant films to aerosols led to reproducible dosing of particles on the films. In film collapse experiments, particle deposition led to slight changes in collapse surface pressure and surface area of both surfactants. However, longer interaction times between particles and Infasurf® films resulted in time-dependent inhibition of surfactant function. When limited to lung relevant surface pressures, particles reduced the maximum surface pressure that could be achieved. This inhibitory effect persisted for all compression-expansion cycles in DPPC, but normal surfactant behavior was restored in Infasurf® films after five cycles. Conclusions: The observation that Infasurf® was able to quickly restore its function after exposure to aerosols under conditions that better mimicked those in vivo suggests that particle

  17. A prospective cohort study among new Chinese coal miners: the early pattern of lung function change

    PubMed Central

    Wang, M; Wu, Z; Du, Q; Petsonk, E; Peng, K; Li, Y; Li, S; Han, G; Atffield, M

    2005-01-01

    Aims: To investigate the early pattern of longitudinal change in forced expiratory volume in 1 second (FEV1) among new Chinese coal miners, and the relation between coal mine dust exposure and the decline of lung function. Methods: The early pattern of lung function changes in 317 newly hired Chinese underground coal miners was compared to 132 referents. This three year prospective cohort study involved a pre-employment and 15 follow up health surveys, including a questionnaire and spirometry tests. Twice a month, total and respirable dust area sampling was done. The authors used a two stage analysis and a linear mixed effects model approach to analyse the longitudinal spirometry data, and to investigate the changes in FEV1 over time, controlling for age, height, pack years of smoking, mean respirable dust concentration, the room temperature during testing, and the groupxtime interaction terms. Results: FEV1 change over time in new miners is non-linear. New miners experience initial rapid FEV1 declines, primarily during the first year of mining, little change during the second year, and partial recovery during the third year. Both linear and quadratic time trends in FEV1 change are highly significant. Smoking miners lost more FEV1 than non-smokers. Referents, all age less than 20 years, showed continued lung growth, whereas the miners who were under age 20 exhibited a decline in FEV1. Conclusion: Dust and smoking affect lung function in young, newly hired Chinese coal miners. FEV1 change over the first three years of employment is non-linear. The findings have implications for both methods and interpretation of medical screening in coal mining and other dusty work: during the first several years of employment more frequent testing may be desirable, and caution is required in interpreting early FEV1 declines. PMID:16234407

  18. Diesel exhaust modulates ozone-induced lung function decrements in healthy human volunteers

    PubMed Central

    2014-01-01

    The potential effects of combinations of dilute whole diesel exhaust (DE) and ozone (O3), each a common component of ambient airborne pollutant mixtures, on lung function were examined. Healthy young human volunteers were exposed for 2 hr to pollutants while exercising (~50 L/min) intermittently on two consecutive days. Day 1 exposures were either to filtered air, DE (300 μg/m3), O3 (0.300 ppm), or the combination of both pollutants. On Day 2 all exposures were to O3 (0.300 ppm), and Day 3 served as a followup observation day. Lung function was assessed by spirometry just prior to, immediately after, and up to 4 hr post-exposure on each exposure day. Functional pulmonary responses to the pollutants were also characterized based on stratification by glutathione S-transferase mu 1 (GSTM1) genotype. On Day 1, exposure to air or DE did not change FEV1 or FVC in the subject population (n = 15). The co-exposure to O3 and DE decreased FEV1 (17.6%) to a greater extent than O3 alone (9.9%). To test for synergistic exposure effects, i.e., in a greater than additive fashion, FEV1 changes post individual O3 and DE exposures were summed together and compared to the combined DE and O3 exposure; the p value was 0.057. On Day 2, subjects who received DE exposure on Day 1 had a larger FEV1 decrement (14.7%) immediately after the O3 exposure than the individuals’ matched response following a Day 1 air exposure (10.9%). GSTM1 genotype did not affect the magnitude of lung function changes in a significant fashion. These data suggest that altered respiratory responses to the combination of O3 and DE exposure can be observed showing a greater than additive manner. In addition, O3-induced lung function decrements are greater with a prior exposure to DE compared to a prior exposure to filtered air. Based on the joint occurrence of these pollutants in the ambient environment, the potential exists for interactions in more than an additive fashion affecting lung physiological

  19. Short-Term Exposure to Air Pollution and Lung Function in the Framingham Heart Study

    PubMed Central

    Ljungman, Petter L.; Wilker, Elissa H.; Gold, Diane R.; Schwartz, Joel D.; Koutrakis, Petros; Washko, George R.; O’Connor, George T.; Mittleman, Murray A.

    2013-01-01

    Rationale: Short-term exposure to ambient air pollution has been associated with lower lung function. Few studies have examined whether these associations are detectable at relatively low levels of pollution within current U.S. Environmental Protection Agency (EPA) standards. Objectives: To examine exposure to ambient air pollutants within EPA standards and lung function in a large cohort study. Methods: We included 3,262 participants of the Framingham Offspring and Third Generation cohorts living within 40 km of the Harvard Supersite monitor in Boston, Massachusetts (5,358 examinations, 1995–2011) who were not current smokers, with previous-day pollutant levels in compliance with EPA standards. We compared lung function (FEV1 and FVC) after previous-day exposure to particulate matter less than 2.5 μm in diameter (PM2.5), nitrogen dioxide (NO2), and ozone (O3) in the “moderate” range of the EPA Air Quality Index to exposure in the “good” range. We also examined linear relationships between moving averages of pollutant concentrations 1, 2, 3, 5, and 7 days before spirometry and lung function. Measurements and Main Results: Exposure to pollutant concentrations in the “moderate” range of the EPA Air Quality Index was associated with a 20.1-ml lower FEV1 for PM2.5 (95% confidence interval [CI], −33.4, −6.9), a 30.6-ml lower FEV1 for NO2 (95% CI, −60.9, −0.2), and a 55.7-ml lower FEV1 for O3 (95% CI, −100.7, −10.8) compared with the “good” range. The 1- and 2-day moving averages of PM2.5, NO2, and O3 before testing were negatively associated with FEV1 and FVC. Conclusions: Short-term exposure to PM2.5, NO2, and O3 within current EPA standards was associated with lower lung function in this cohort of adults. PMID:24200465

  20. Exhaled nitric oxide levels and lung function changes of underground coal miners in Newcastle, Australia.

    PubMed

    Liu, Xiaohui; Salter, Amy; Thomas, Paul; Leigh, James; Wang, He

    2010-01-01

    The possibility of exhaled nitric oxide (eNO) in combination with lung function as a marker of airway inflammation produced by coal mining exposure was determined presuming that workers exposed to airborne hazards would possess different concentrations of eNO and decreased lung function indices, relative to control subjects recruited from the same area. The effect of smoking was also considered. A study (exposed) group comprising 186 male subjects (aged 19-58 yr) was recruited from Newcastle coal mining companies with 86 male subjects (aged 20-64 yr) from the same area, but working outside of the coal mining location, serving as controls. The parameters examined were eNO, lung function, and variables derived from an interview-administered questionnaire survey. After adjustment for age, body weight, and smoking status, no significant differences between exposed coal mining workers and controls were found for various lung function parameters. However, the exposed group was shown to have significantly lower concentrations of eNO. In the exposed group, forced expiratory volume in 1 s (FEV(1)), forced vital capacity (FVC), and FEV(1) (%) predicted were found to be significantly different between nonsmokers and smokers. The concentrations of eNO were not significantly different between smoking and nonsmokers within the exposed group. The consideration of nonsmokers alone showed that eNO was significantly lower in the exposed group compared to the control group. The consideration of smokers alone found that eNO was significantly lower in exposed subjects. In the exposed group, no significant association was detected between eNO levels and underground work duration but a significant negative association was shown between eNO and age. Data suggest that exposure to airborne hazards in coal mining is not significantly associated with lung function changes but is correlated with decreased eNO concentrations in exposed workers. While underground work duration was not found to

  1. The Diabetic Lung - A New Target Organ?

    PubMed Central

    Pitocco, Dario; Fuso, Leonello; Conte, Emanuele G.; Zaccardi, Francesco; Condoluci, Carola; Scavone, Giuseppe; Incalzi, Raffaele Antonelli; Ghirlanda, Giovanni

    2012-01-01

    Several abnormalities of the respiratory function have been reported in patients with type 1 and type 2 diabetes. These abnormalities concern lung volume, pulmonary diffusing capacity, control of ventilation, bronchomotor tone, and neuroadrenergic bronchial innervation. Many hypotheses have emerged, and characteristic histological changes have been described in the "diabetic lung", which could explain this abnormal respiratory function. Given the specific abnormalities in diabetic patients, the lung could thus be considered as a target organ in diabetes. Although the practical implications of these functional changes are mild, the presence of an associated acute or chronic pulmonary and/or cardiac disease could determine severe respiratory derangements in diabetic patients. Another clinical consequence of the pulmonary involvement in diabetes is the accelerated decline in respiratory function. The rate of decline in respiratory function in diabetics has been found to be two-to-three times faster than in normal non-smoking subjects, as reported in longitudinal studies. This finding, together with the presence of anatomical and biological changes similar to those described in the aging lung, indicates that the "diabetic lung" could even be considered a model of accelerated aging. This review describes and analyses the current insight into the relationship of diabetes and lung disease, and suggests intensifying research into the lung as a possible target organ in diabetes. PMID:22972442

  2. Effects of etomidate and propofol on immune function in patients with lung adenocarcinoma

    PubMed Central

    Liu, Jiapeng; Dong, Wei; Wang, Tao; Liu, Liang; Zhan, Long; Shi, Yifei; Han, Jiange

    2016-01-01

    Objective: To investigate the effects of etomidate and propofol on immune function in patients with lung adenocarcinoma. Methods: Sixty patients who were scheduled for lung cancer surgery under general anesthesia were studied. The patients were randomly divided into an etomidate total intravenous anesthesia group (group E) and a propofol total intravenous anesthesia group (group P), with 30 cases in each group. Results: Within group comparison: The percentage of CD4+ in the two groups was significantly reduced at 24 hours post-operation (T2) compared with the percentage before surgery, whereas the percentage of CD8+ was higher at T2. Between group comparison: The CD4+ percentage of group E was higher than that of group P (P < 0.05) at T2, whereas the CD8+ percentage was lower than that of group P (P < 0.05) at T1. Conclusion: Using etomidate for anesthesia has less of an effect on immune function in patients with lung adenocarcinoma. PMID:28078046

  3. Plasma gelsolin improves lung host defense against pneumonia by enhancing macrophage NOS3 function.

    PubMed

    Yang, Zhiping; Chiou, Terry Ting-Yu; Stossel, Thomas P; Kobzik, Lester

    2015-07-01

    Plasma gelsolin (pGSN) functions as part of the "extracellular actin-scavenging system," but its potential to improve host defense against infection has not been studied. In a mouse model of primary pneumococcal pneumonia, recombinant human pGSN (rhu-pGSN) caused enhanced bacterial clearance, reduced acute inflammation, and improved survival. In vitro, rhu-pGSN rapidly improved lung macrophage uptake and killing of bacteria (Streptococcus pneumoniae, Escherichia coli, and Francisella tularensis). pGSN triggers activating phosphorylation (Ser(1177)) of macrophage nitric oxide synthase type III (NOS3), an enzyme with important bactericidal functions in lung macrophages. rhu-pGSN failed to enhance bacterial killing by NOS3(-/-) macrophages in vitro or bacterial clearance in NOS3(-/-) mice in vivo. Prophylaxis with immunomodulators may be especially relevant for patients at risk for secondary bacterial pneumonia, e.g., after influenza. Treatment of mice with pGSN challenged with pneumococci on postinfluenza day 7 (the peak of enhanced susceptibility to secondary infection) caused a ∼15-fold improvement in bacterial clearance, reduced acute neutrophilic inflammation, and markedly improved survival, even without antibiotic therapy. pGSN is a potential immunomodulator for improving lung host defense against primary and secondary bacterial pneumonia.

  4. Functional and cytometric examination of different human lung epithelial cell types as drug transport barriers

    PubMed Central

    Min, Kyoung Ah; Rosania, Gus R.; Kim, Chong-Kook; Shin, Meong Cheol

    2016-01-01

    To develop inhaled medications, various cell culture models have been used to examine the transcellular transport or cellular uptake properties of small molecules. For the reproducible high throughput screening of the inhaled drug candidates, a further verification of cell architectures as drug transport barriers can contribute to establishing appropriate in vitro cell models. In the present study, side-by-side experiments were performed to compare the structure and transport function of three lung epithelial cells (Calu-3, normal human bronchial primary cells (NHBE), and NL-20). The cells were cultured on the nucleopore membranes in the air-liquid interface (ALI) culture conditions, with cell culture medium in the basolateral side only, starting from day 1. In transport assays, paracellular transport across all three types of cells appeared to be markedly different with the NHBE or Calu-3 cells, showing low paracellular permeability and high TEER values, while the NL-20 cells showed high paracellular permeability and low TEER. Quantitative image analysis of the confocal microscope sections further confirmed that the Calu-3 cells formed intact cell monolayers in contrast to the NHBE and NL-20 cells with multilayers. Among three lung epithelial cell types, the Calu-3 cell cultures under the ALI condition showed optimal cytometric features for mimicking the biophysical characteristics of in vivo airway epithelium. Therefore, the Calu-3 cell monolayers could be used as functional cell barriers for the lung-targeted drug transport studies. PMID:26746641

  5. Lung function impact from working in the pre-revolution Libyan quarry industry.

    PubMed

    Draid, Marwan M; Ben-Elhaj, Khaled M; Ali, Ashraf M; Schmid, Kendra K; Gibbs, Shawn G

    2015-05-07

    The purpose of this study was to determine the lung impact from working within the Libyan quarry industry, and if the length of work impacted the degree of degradation. Eighty three workers from eight silica quarries in the Nafusa Mountains of Libya opted to participate. These quarries were working the upper cretaceous geological structure. Eighty-five individuals who lived in Gharyan City with no affiliation to quarry operations participated as controls. Spirometry variables evaluated were Forced Vital Capacity (FVC), Forced Expiratory Volume at 1.0 second (FEV1), FVC/FEV1 and Peak Expiratory Flow (PEF). Control and exposed groups had no differences in terms of height, weight, or smoking status (p = 0.18, 0.20, 0.98, respectively). Prior to adjustment for other variables, FVC, FEV1, and PEF are all significantly lower in the exposed group (p = 0.003, 0.009, 0.03, respectively). After adjustment for age, height, weight, and smoking status, there remain significant differences between the control and exposed groups for FVC, FEV1, and PEF. This analysis demonstrated that exposure to quarry dust has a detrimental effect on lung function, and that pre-revolution Libyan quarry workers were being exposed. This study shows that any exposure is harmful, as the reduction in lung function was not significantly associated with years of exposure.

  6. Carboxyl-terminal modulator protein induces apoptosis by regulating mitochondrial function in lung cancer cells.

    PubMed

    Hwang, Soon-Kyung; Minai-Tehrani, Arash; Yu, Kyeong-Nam; Chang, Seung-Hee; Kim, Ji-Eun; Lee, Kee-Ho; Park, Jongsun; Beck, George R; Cho, Myung-Haing

    2012-05-01

    Serine/threonine protein kinase B (PKB/Akt) is involved in cell survival and growth. Carboxyl-terminal modulator protein (CTMP), a novel Akt binding partner, prevents Akt activation at the plasma membrane in response to various stimuli, and thus possesses a tumor suppressor-like function. In a previous study, we have demonstrated that CTMP inhibits tumor progression by facilitating apoptosis in a mouse lung cancer model. However, the precise mechanism of CTMP-induced apoptosis remains to be elucidated. The present study was performed to examine the role of CTMP in mitochondrial-mediated apoptosis and regulation of mitochondrial function in human lung carcinoma cells. Our results showed that CTMP altered mitochondrial morphology and caused the release of cytochrome c by inhibiting OPA1 expression. Additionally, CTMP facilitated mitochondrial-mediated apoptosis by inhibiting heat-shock protein 27 and preventing cytochrome c interaction with Apaf-1. Our data suggest that CTMP may therefore play a critical role in mitochondrial-mediated apoptosis in lung cancer cells.

  7. Lung Function Impact from Working in the Pre-Revolution Libyan Quarry Industry

    PubMed Central

    Draid, Marwan M.; Ben-Elhaj, Khaled M.; Ali, Ashraf M.; Schmid, Kendra K.; Gibbs, Shawn G.

    2015-01-01

    The purpose of this study was to determine the lung impact from working within the Libyan quarry industry, and if the length of work impacted the degree of degradation. Eighty three workers from eight silica quarries in the Nafusa Mountains of Libya opted to participate. These quarries were working the upper cretaceous geological structure. Eighty-five individuals who lived in Gharyan City with no affiliation to quarry operations participated as controls. Spirometry variables evaluated were Forced Vital Capacity (FVC), Forced Expiratory Volume at 1.0 second (FEV1), FVC/FEV1 and Peak Expiratory Flow (PEF). Control and exposed groups had no differences in terms of height, weight, or smoking status (p = 0.18, 0.20, 0.98, respectively). Prior to adjustment for other variables, FVC, FEV1, and PEF are all significantly lower in the exposed group (p = 0.003, 0.009, 0.03, respectively). After adjustment for age, height, weight, and smoking status, there remain significant differences between the control and exposed groups for FVC, FEV1, and PEF. This analysis demonstrated that exposure to quarry dust has a detrimental effect on lung function, and that pre-revolution Libyan quarry workers were being exposed. This study shows that any exposure is harmful, as the reduction in lung function was not significantly associated with years of exposure. PMID:25961801

  8. The impact of recurrent acute chest syndrome on the lung function of young adults with sickle cell disease.

    PubMed

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

    2010-12-01

    The aim of this study was to assess the impact of recurrent acute chest syndrome (ACS) episodes on the lung function of young adults with sickle cell disease (SCD). Our prospective study included 80 SCD adults [26 with recurrent acute chest syndrome (ACS)] and 80 ethnically matched controls aged between 18 and 28 years. Lung function (spirometry and lung volumes) was measured and the results were expressed as the percentage predicted for height. Bronchial hyperresponsiveness (BHR) was assessed by the response to either a bronchodilator or an exercise challenge. The adults with recurrent ACS (two or more ACS episodes) had lower median forced vital capacity (74 vs. 83%, p = 0.03), forced expiratory volume in 1 s (79 vs. 90%, p < 0.03), and total lung capacity (69 vs. 81%, p = 0.04) than SCD adults who had one or no ACS episodes. The greater the number of ACS episodes, the greater the reduction in lung function (p = 0.001). The adults with SCD had lower median forced vital capacity (81 vs. 106%), forced expiratory volume in 1 s (85 vs. 107%), and total lung capacity (80 vs. 87%) than the controls (p < 0.001). Similar numbers in each group had BHR (p = 0.2). The prevalence of restrictive ventilatory defect in the patients with SCD was almost double that of the controls (p = 0.004). Young adults with SCD have worse lung function than ethnically matched controls, particularly if they have suffered recurrent ACS episodes.

  9. Functional Gene Correction for Cystic Fibrosis in Lung Epithelial Cells Generated From Patient iPSCs

    PubMed Central

    Firth, Amy L; Menon, Tushar; Parker, Gregory S; Qualls, Susan J; Lewis, Benjamin M; Ke, Eugene; Dargitz, Carl T; Wright, Rebecca; Khanna, Ajai; Gage, Fred H; Verma, Inder M

    2015-01-01

    SUMMARY Lung disease is a major cause of death in the USA, with current therapeutic approaches only serving to manage symptoms. The most common chronic and life-threatening genetic disease of the lung is Cystic fibrosis (CF) caused by mutations in the cystic fibrosis transmembrane regulator (CFTR). We have generated induced pluripotent stem cells (iPSC) from CF patients carrying a homozygous deletion of F508 in the CFTR gene, which results in defective processing of CFTR to the cell membrane. This mutation was precisely corrected using CRISPR to target corrective sequences to the endogenous CFTR genomic locus, in combination with a completely excisable selection system which significantly improved the efficiency of this correction. The corrected iPSC were subsequently differentiated to mature airway epithelial cells where recovery of normal CFTR expression and function was demonstrated. This isogenic iPSC-based model system for CF could be adapted for the development of new therapeutic approaches. PMID:26299960

  10. Functional anatomy of the lungs of the green lizard, Lacerta viridis.

    PubMed

    Meban, C

    1978-02-01

    The gas-exchange area in the lung of Lacerta viridis has been studied by light microscopy and electron microscopy. The interior of the lung in this species is partitioned into air sacs by radially disposed septa. The surfaces of each septum are covered by a continuous epithelium, the cells of which are termed 'pneumonocytes'. Deep to the epithelium there is a close-meshed plexus of capillaries. The middle layer of the septum contains smooth muscle and fibrous tissue. Two varieties of pneumonocytes can be identified. The type I cells are squamous and give off attenuated sheets of cytoplasm which spread widely over the septal surface; these sheets contain few organelles. The type II cells are more compact and possess many organelles; their osmiophilic inclusion bodies are especially conspicuous. The pulmonary capillaries of Lacerta are evaginated into the air sacs and often display marked attenuation of their endothelium. The possible functional significance of these features is discussed.

  11. Structure and Function of the Mucus Clearance System of the Lung

    PubMed Central

    Button, Brenda M.; Button, Brian

    2013-01-01

    In cystic fibrosis (CF), a defect in ion transport results in thick and dehydrated airway mucus, which is difficult to clear, making such patients prone to chronic inflammation and bacterial infections. Physiotherapy using a variety of airway clearance techniques (ACTs) represents a key treatment regime by helping clear the airways of thickened, adhered, mucus and, thus, reducing the impact of lung infections and improving lung function. This article aims to bridge the gap between our understanding of the physiological effects of mechanical stresses elicited by ACTs on airway epithelia and the reported effectiveness of ACTs in CF patients. In the first part of this review, the effects of mechanical stress on airway epithelia are discussed in relation to changes in ion transport and stimulation in airway surface layer hydration. The second half is devoted to detailing the most commonly used ACTs to stimulate the removal of mucus from the airways of patients with CF. PMID:23751214

  12. Relation between dust exposure and lung function in miners and ex-miners.

    PubMed Central

    Soutar, C A; Hurley, J F

    1986-01-01

    A sample of men working in the British coal industry in the 1950s has been followed up and examined 22 years later. The relations between lung function and individual cumulative exposure to respirable dust have been studied in 1867 men who were still working in the industry at the time of follow up and 2192 men who had left. Levels of forced expired volume in one second (FEV1), forced vital capacity (FVC), and FEV1/FVC ratio at follow up were found to be inversely related to exposure to respirable dust after allowing for other factors, even in men without pneumoconiosis. The magnitude of this estimated effect was equivalent to a loss of 228 ml FEV1 in response to an exposure of 300 gh/m3, a moderately high exposure for this group. Ex-miners aged under 65 had worse lung function than miners on average, suggesting that ill health had encouraged some of these men to leave the industry. Whereas a more severe response to dust exposure among ex-miners under 65 was suggested, this difference could easily have arisen by chance. The presence of symptoms of chronic bronchitis was associated with reduced levels of lung function, however, and, additionally, ex-miners under 65 with chronic bronchitis showed a more severe response of the FVC to dust exposure than miners without these symptoms. Among these ex-miners with chronic bronchitis a small group of men who had taken other jobs showed a much more severe effect of dust exposure on their lung function than the average, likely in heavily exposed men to contribute importantly to disability. Men in this group who had given up smoking showed and even more severe effect of dust exposure, equivalent to a loss of 940 ml FEV1 in response to an exposure of 300 gh/m3. These results indicate that exposure to respirable dust can occasionally cause severe respiratory impairment in the absence of progressive massive fibrosis. Dust exposure was related to a parallel reduction of FEV1 and FVC, implying that the pathology of dust induced

  13. Effect of surfactant on regional lung function in an experimental model of respiratory distress syndrome in rabbit.

    PubMed

    Bayat, Sam; Porra, Liisa; Broche, Ludovic; Albu, Gergely; Malaspinas, Iliona; Doras, Camille; Strengell, Satu; Peták, Ferenc; Habre, Walid

    2015-08-01

    We assessed the changes in regional lung function following instillation of surfactant in a model of respiratory distress syndrome (RDS) induced by whole lung lavage and mechanical ventilation in eight anaesthetized, paralyzed, and mechanically ventilated New Zealand White rabbits. Regional specific ventilation (sV̇) was measured by K-edge subtraction synchrotron computed tomography during xenon washin. Lung regions were classified as poorly aerated (PA), normally aerated (NA), or hyperinflated (HI) based on regional density. A functional category was defined within each class based on sV̇ distribution (High, Normal, and Low). Airway resistance (Raw), respiratory tissue damping (G), and elastance (H) were measured by forced oscillation technique at low frequencies before and after whole lung saline lavage-induced (100 ml/kg) RDS, and 5 and 45 min after intratracheal instillation of beractant (75 mg/kg). Surfactant instillation improved Raw, G, and H (P < 0.05 each), and gas exchange and decreased atelectasis (P < 0.001). It also significantly improved lung aeration and ventilation in atelectatic lung regions. However, in regions that had remained normally aerated after lavage, it decreased regional aeration and increased sV̇ (P < 0.001) and sV̇ heterogeneity. Although surfactant treatment improved both central airway and tissue mechanics and improved regional lung function of initially poorly aerated and atelectatic lung, it deteriorated regional lung function when local aeration was normal prior to administration. Local mechanical and functional heterogeneity can potentially contribute to the worsening of RDS and gas exchange. These data underscore the need for reassessing the benefits of routine prophylactic vs. continuous positive airway pressure and early "rescue" surfactant therapy in very immature infants.

  14. In utero and early childhood exposure to arsenic decreases lung function in children

    PubMed Central

    Recio-Vega, Rogelio; Gonzalez-Cortes, Tania; Olivas-Calderon, Edgar; Lantz, R. Clark; Gandolfi, A. Jay; Gonzalez-De Alba, Cesar

    2016-01-01

    Background The lung is a target organ for adverse health outcomes following exposure to arsenic. Several studies have reported a high prevalence of respiratory symptoms and diseases in subjects highly exposed to arsenic through drinking water, however, most studies to date has been performed in exposed adults, with little information on respiratory effects in children. The objective of the study was to evaluate the association between urinary levels of arsenic and its metabolites with lung function in children exposed in utero and in early childhood to high arsenic levels through drinking water. Methods A total of 358 healthy children were included in our study. Individual exposure was assessed based on urinary concentration of inorganic arsenic. Lung function was assessed by spirometry. Results Participants were exposed since pregnancy until early childhood to an average water As concentration of 152.13 μg/L. The mean urinary arsenic level registered in the studied subjects was 141.2 μg/L and only 16.7% had a urinary concentration below the national concern level. Forced vital capacity was significantly decreased in the studied population and it was negatively associated with the percent of inorganic arsenic. More than 57% of the subjects had a restrictive spirometric pattern. The urinary As level was higher in those children with restrictive lung patterns when compared with the levels registered in subjects with normal spirometric patterns. Conclusion Exposure to arsenic through drinking water during in utero and early life was associated with a decrease in FVC and with a restrictive spirometric pattern in the children evaluated. PMID:25131850

  15. Exercise tolerance, lung function abnormalities, anemia, and cardiothoracic ratio in sickle cell patients.

    PubMed

    van Beers, Eduard J; van der Plas, Mart N; Nur, Erfan; Bogaard, Harm-Jan; van Steenwijk, Reindert P; Biemond, Bart J; Bresser, Paul

    2014-08-01

    Many patients with sickle cell disease (SCD) have a reduced exercise capacity and abnormal lung function. Cardiopulmonary exercise testing (CPET) can identify causes of exercise limitation. Forty-four consecutive SCD patients (27 HbSS, 11 HbSC, and 6 HbS-beta thalassemia) with a median age (interquartile range) of 26 (21-41) years underwent pulmonary function tests, CPET, chest x-ray, and echocardiography to further characterize exercise limitation in SCD. Peak oxygen uptake (V'O2 -peak), expressing maximum exercise capacity, was decreased in 83% of the studied patients. V'O2 -peak correlated with hemoglobin levels (R = 0.440, P = 0.005), forced vital capacity (FVC) (R = 0.717, P < 0.0001). Cardiothoracic ratio on chest x-ray inversely correlated with FVC (R = -0.637, P < 0.001). According to criteria for exercise limitation, the patients were limited in exercise capacity due to anemia (n = 17), cardiovascular dysfunction (n = 2), musculoskeletal function (n = 10), pulmonary ventilatory abnormalities (n = 1), pulmonary vascular exercise limitation (n = 1), and poor effort (n = 3). In the present study we demonstrate that anemia is the most important determinant of reduced exercise tolerance observed in SCD patients without signs of pulmonary hypertension. We found a strong correlation between various parameters of lung volume and cardiothoracic ratio and we hypothesize that cardiomegaly and relative small chest size may be important causes of the impairment in pulmonary function, that is, reduced long volumes and diffusion capacity, in SCD. Taking into account anthropomorphic differences between SCD patients and controls could help to interpret lung function studies in SCD better.

  16. Joint effects of smoking and sedentary lifestyle on lung function in African Americans: the Jackson Heart Study cohort.

    PubMed

    Campbell Jenkins, Brenda W; Sarpong, Daniel F; Addison, Clifton; White, Monique S; Hickson, Demarc A; White, Wendy; Burchfiel, Cecil

    2014-01-28

    This study examined: (a) differences in lung function between current and non current smokers who had sedentary lifestyles and non sedentary lifestyles and (b) the mediating effect of sedentary lifestyle on the association between smoking and lung function in African Americans. Sedentary lifestyle was defined as the lowest quartile of the total physical activity score. The results of linear and logistic regression analyses revealed that non smokers with non sedentary lifestyles had the highest level of lung function, and smokers with sedentary lifestyles had the lowest level. The female non-smokers with sedentary lifestyles had a significantly higher FEV1% predicted and FVC% predicted than smokers with non sedentary lifestyles (93.3% vs. 88.6%; p = 0.0102 and 92.1% vs. 86.9%; p = 0.0055 respectively). FEV1/FVC ratio for men was higher in non smokers with sedentary lifestyles than in smokers with non sedentary lifestyles (80.9 vs. 78.1; p = 0.0048). Though smoking is inversely associated with lung function, it seems to have a more deleterious effect than sedentary lifestyle on lung function. Physically active smokers had higher lung function than their non physically active counterparts.

  17. Functional imaging of murine hearts using accelerated self-gated UTE cine MRI.

    PubMed

    Motaal, Abdallah G; Noorman, Nils; de Graaf, Wolter L; Hoerr, Verena; Florack, Luc M J; Nicolay, Klaas; Strijkers, Gustav J

    2015-01-01

    We introduce a fast protocol for ultra-short echo time (UTE) Cine magnetic resonance imaging (MRI) of the beating murine heart. The sequence involves a self-gated UTE with golden-angle radial acquisition and compressed sensing reconstruction. The self-gated acquisition is performed asynchronously with the heartbeat, resulting in a randomly undersampled kt-space that facilitates compressed sensing reconstruction. The sequence was tested in 4 healthy rats and 4 rats with chronic myocardial infarction, approximately 2 months after surgery. As a control, a non-accelerated self-gated multi-slice FLASH sequence with an echo time (TE) of 2.76 ms, 4.5 signal averages, a matrix of 192 × 192, and an acquisition time of 2 min 34 s per slice was used to obtain Cine MRI with 15 frames per heartbeat. Non-accelerated UTE MRI was performed with TE = 0.29 ms, a reconstruction matrix of 192 × 192, and an acquisition time of 3 min 47 s per slice for 3.5 averages. Accelerated imaging with 2×, 4× and 5× undersampled kt-space data was performed with 1 min, 30 and 15 s acquisitions, respectively. UTE Cine images up to 5× undersampled kt-space data could be successfully reconstructed using a compressed sensing algorithm. In contrast to the FLASH Cine images, flow artifacts in the UTE images were nearly absent due to the short echo time, simplifying segmentation of the left ventricular (LV) lumen. LV functional parameters derived from the control and the accelerated Cine movies were statistically identical.

  18. Ground Test of the Urine Processing Assembly for Accelerations and Transfer Functions

    NASA Technical Reports Server (NTRS)

    Houston, Janice; Almond, Deborah F. (Technical Monitor)

    2001-01-01

    This viewgraph presentation gives an overview of the ground test of the urine processing assembly for accelerations and transfer functions. Details are given on the test setup, test data, data analysis, analytical results, and microgravity assessment. The conclusions of the tests include the following: (1) the single input/multiple output method is useful if the data is acquired by tri-axial accelerometers and inputs can be considered uncorrelated; (2) tying coherence with the matrix yields higher confidence in results; (3) the WRS#2 rack ORUs need to be isolated; (4) and future work includes a plan for characterizing performance of isolation materials.

  19. Potentially Functional Polymorphisms in POU5F1 Gene Are Associated with the Risk of Lung Cancer in Han Chinese.

    PubMed

    Niu, Rui; Wang, Yuzhuo; Zhu, Meng; Wen, Yifan; Sun, Jie; Shen, Wei; Cheng, Yang; Zhang, Jiahui; Jin, Guangfu; Ma, Hongxia; Hu, Zhibin; Shen, Hongbing; Dai, Juncheng

    2015-01-01

    POU5F1 is a key regulator of self-renewal and differentiation in embryonic stem cells and may be associated with initiation, promotion, and progression in cancer. We hypothesized that functional polymorphisms in POU5F1 may play an important role in modifying the lung cancer risk. To test this hypothesis, we conducted a case-control study to explore the association between 17 potentially functional SNPs in POU5F1 gene and the lung cancer risk in 1,341 incident lung cancer cases and 1,982 healthy controls in a Chinese population. We found that variant alleles of rs887468 and rs3130457 were significantly associated with increased risk of lung cancer after multiple comparison (OR = 1.29, 95% CI: 1.11-1.51, P fdr = 0.017 for rs887468; OR = 1.29, 95% CI: 1.10-1.51, P fdr = 0.034 for rs3130457, resp.). In addition, we detected a significant interaction between rs887468 genotypes and smoking status on lung cancer risk (P = 0.017). Combined analysis of these 2 SNPs showed a significant allele-dosage association between the number of risk alleles and increased risk of lung cancer (P trend < 0.001). These findings indicate that potentially functional polymorphisms in POU5F1 gene may contribute to lung cancer susceptibility in a Chinese population.

  20. Dynamic tracheal occlusion improves lung morphometrics and function in the fetal lamb model of congenital diaphragmatic hernia

    PubMed Central

    Jelin, Eric B.; Etemadi, Mozziyar; Encinas, Jose; Schecter, Samuel C.; Chapin, Cheryl; Wu, Jianfeng; Guevara-Gallardo, Salvador; Nijagal, Amar; Gonzales, Kelly D.; Ferrier, William T.; Roy, Shuvo; Miniati, Doug

    2011-01-01

    Background Congenital diaphragmatic hernia (CDH) is associated with significant neonatal morbidity and mortality. Although prenatal complete tracheal occlusion (cTO) causes hypoplastic CDH lungs to enlarge, improved lung function has not been demonstrated. Furthermore, cTO interferes with the dynamic pressure change and fluid flow associated with fetal breathing. Purpose To assess a novel dynamic tracheal occlusion (dTO) device that preserves pressure changes and fluid flow. Methods In this pilot study, CDH was created in fetal lambs at 65 days gestational age (GA). At 110 days GA, a cTO device (n=3) or a dTO device (n=4) was placed in the fetal trachea. At 135 days GA, lambs were delivered and resuscitated. Unoperated lamb co-twins (n=5), sham thoracotomy lambs (n=2), and untreated CDH lambs (n=3) served as controls. Results Tracheal opening pressure, lung volume, lung fluid total protein, and phospholipid were significantly higher in the cTO group than in the dTO and unoperated control groups. Maximal oxygenation and lung compliance were significantly lower in the cTO group when compared to the unoperated control and dTO groups. Conclusion Preliminary results suggest that in the fetal lamb CDH model, dTO restores normal lung morphometrics and function, whereas cTO leads to enlarged but less functional lungs. PMID:21683214

  1. Potentially Functional Polymorphisms in POU5F1 Gene Are Associated with the Risk of Lung Cancer in Han Chinese

    PubMed Central

    Niu, Rui; Wang, Yuzhuo; Zhu, Meng; Wen, Yifan; Sun, Jie; Shen, Wei; Cheng, Yang; Zhang, Jiahui; Jin, Guangfu; Ma, Hongxia; Hu, Zhibin; Shen, Hongbing; Dai, Juncheng

    2015-01-01

    POU5F1 is a key regulator of self-renewal and differentiation in embryonic stem cells and may be associated with initiation, promotion, and progression in cancer. We hypothesized that functional polymorphisms in POU5F1 may play an important role in modifying the lung cancer risk. To test this hypothesis, we conducted a case-control study to explore the association between 17 potentially functional SNPs in POU5F1 gene and the lung cancer risk in 1,341 incident lung cancer cases and 1,982 healthy controls in a Chinese population. We found that variant alleles of rs887468 and rs3130457 were significantly associated with increased risk of lung cancer after multiple comparison (OR = 1.29, 95% CI: 1.11–1.51, Pfdr = 0.017 for rs887468; OR = 1.29, 95% CI: 1.10–1.51, Pfdr = 0.034 for rs3130457, resp.). In addition, we detected a significant interaction between rs887468 genotypes and smoking status on lung cancer risk (P = 0.017). Combined analysis of these 2 SNPs showed a significant allele-dosage association between the number of risk alleles and increased risk of lung cancer (Ptrend < 0.001). These findings indicate that potentially functional polymorphisms in POU5F1 gene may contribute to lung cancer susceptibility in a Chinese population. PMID:26824036

  2. Influence of donor–recipient gender mismatch on graft function and survival following lung transplantation†

    PubMed Central

    Alvarez, Antonio; Moreno, Paula; Illana, Jennifer; Espinosa, Dionisio; Baamonde, Carlos; Arango, Elisabet; Algar, Francisco Javier; Salvatierra, Angel

    2013-01-01

    OBJECTIVES In current practice, donors and recipients are not matched for gender in lung transplantation. However, some data have suggested a possible effect of gender combinations on lung transplant outcomes. We examined whether donor–recipient (D/R) gender mismatch is related to adverse outcomes after lung transplantation in terms of early and long-term graft function and survival. METHODS We reviewed 256 donors and lung transplant recipients over a 14-year period. Patients were distributed into four groups: Group A (D/R: female/female), Group B (D/R: male/male), Group C (D/R: female/male), Group D (D/R: male/female). Donor and recipient variables were compared among groups, including early graft function, 30-day mortality, freedom from bronchiolitis obliterans syndrome (BOS), and long-term survival. RESULTS Group A: 57 (22%), Group B: 99 (39%), Group C: 62 (24%), Group D: 38 (15%) transplants (P = 0.001). Donor age was 29 ± 14, 27 ± 12, 33 ± 13 and 23 ± 12 years for Groups A, B, C and D, respectively (P = 0.004). Recipient age was 31 ± 15, 44 ± 17, 42 ± 16 and 30 ± 16 years for Groups A, B, C and D, respectively (P = 0.000). PaO2/FiO2 (mmHg) 24 h post-transplant was: Group A: 276 ± 144, Group B: 297 ± 131, Group C: 344 ± 133 and Group D: 238 ± 138 (P = 0.015). Primary graft dysfunction developed in 23, 14, 17 and 21% of recipients from Groups A, B, C and D, respectively (P = 0.45). Operative mortality was 4.4, 6.5, 5.2 and 2%, for recipients from Groups A, B, C and D, respectively (P = 0.66). Freedom from BOS was 73, 59 and 36% for gender-matched transplants vs 76, 67 and 40% for gender-mismatched transplants at 3, 5 and 10 years, respectively (P = 0.618), without differences among groups. A non-significant survival benefit was observed for female recipients, irrespective of the donor gender. CONCLUSIONS Donor–recipient gender mismatch does not have a negative impact on early graft function and mortality following lung transplantation. There is a

  3. Lung function, atopy, and chronic exposure to air pollution in schoolchildren living in two cities of different air quality

    NASA Astrophysics Data System (ADS)

    Gurzau, Eugen S.; Gurzau, Anca; Muresan, Marius; Bodor, Ecaterina; Zehan, Zoe; Radulescu, Nicolae

    1993-03-01

    The question of a causative interrelation between air pollution and respiratory status has received considerable attention by the mass media in our country. Schoolchildren aged 7 to 11 living in two communities with different levels of air pollution were studied. The parents of these children filled out a health questionnaire. The prevalence of respiratory symptoms and pulmonary diseases was found to be significantly higher among children growing up in the polluted area (Tirnaveni) as compared with the low-pollution area (Dej). Lung function tests point out FEF25-75 disorders (and other lung disorders) at higher frequencies in schoolchildren living in the polluted area. Over 90% of schoolchildren living in the polluted area. Over 90% of schoolchildren with lung function disorders had a positive response to bronchodilatation. Of the schoolchildren with lung function disorders, 75.47% (p < 0,001) were atopic all of whom were sensitized to the down and house-dust.

  4. Accelerating Scientific Advancement for Pediatric Rare Lung Disease Research. Report from a National Institutes of Health-NHLBI Workshop, September 3 and 4, 2015.

    PubMed

    Young, Lisa R; Trapnell, Bruce C; Mandl, Kenneth D; Swarr, Daniel T; Wambach, Jennifer A; Blaisdell, Carol J

    2016-12-01

    Pediatric rare lung disease (PRLD) is a term that refers to a heterogeneous group of rare disorders in children. In recent years, this field has experienced significant progress marked by scientific discoveries, multicenter and interdisciplinary collaborations, and efforts of patient advocates. Although genetic mechanisms underlie many PRLDs, pathogenesis remains uncertain for many of these disorders. Furthermore, epidemiology and natural history are insufficiently defined, and therapies are limited. To develop strategies to accelerate scientific advancement for PRLD research, the NHLBI of the National Institutes of Health convened a strategic planning workshop on September 3 and 4, 2015. The workshop brought together a group of scientific experts, intramural and extramural investigators, and advocacy groups with the following objectives: (1) to discuss the current state of PRLD research; (2) to identify scientific gaps and barriers to increasing research and improving outcomes for PRLDs; (3) to identify technologies, tools, and reagents that could be leveraged to accelerate advancement of research in this field; and (4) to develop priorities for research aimed at improving patient outcomes and quality of life. This report summarizes the workshop discussion and provides specific recommendations to guide future research in PRLD.

  5. Exercise testing in severe emphysema: association with quality of life and lung function.

    PubMed

    Brown, Cynthia D; Benditt, Joshua O; Sciurba, Frank C; Lee, Shing M; Criner, Gerard J; Mosenifar, Zab; Shade, David M; Slivka, William A; Wise, Robert A

    2008-04-01

    Six-minute walk testing (6MWT) and cardiopulmonary exercise testing (CPX) are used to evaluate impairment in emphysema. However, the extent of impairment in these tests as well as the correlation of these tests with each other and lung function in advanced emphysema is not well characterized. During screening for the National Emphysema Treatment Trial, maximum ergometer CPX and 6MWT were performed in 1,218 individuals with severe COPD with an average FEV(1) of 26.9 +/- 7.1 % predicted. Predicted values for 6MWT and CPX were calculated from reference equations. Correlation coefficients and multivariable regression models were used to determine the association between lung function, quality of life (QOL) scores, and exercise measures. The two forms of exercise testing were correlated with each other (r = 0.57, p < 0.0001). However, the impairment of performance on CPX was greater than on the 6MWT (27.6 +/- 16.8 vs. 67.9 +/- 18.9 % predicted). Both exercise tests had similar correlation with measures of QOL, but maximum exercise capacity was better correlated with lung function measures than 6-minute walk distance. After adjustment, 6MWD had a slightly greater association with total SGRQ score than maximal exercise (effect size 0.37 +/- 0.04 vs. 0.25 +/- 0.03 %predicted/unit). Despite advanced emphysema, patients are able to maintain 6MWD to a greater degree than maximum exercise capacity. Moreover, the 6MWT may be a better test of functional capacity given its greater association with QOL measures whereas CPX is a better test of physiologic impairment.

  6. Bronchodilator response of advanced lung function parameters depending on COPD severity

    PubMed Central

    Jarenbäck, Linnea; Eriksson, Göran; Peterson, Stefan; Ankerst, Jaro; Bjermer, Leif; Tufvesson, Ellen

    2016-01-01

    Background COPD is defined as partly irreversible airflow obstruction. The response pattern of bronchodilators has not been followed in advanced lung function parameters. Purpose The aim of this study was to investigate bronchodilator response pattern in advanced lung function parameters in a continuous fashion along forced expiratory volume in 1 second (FEV1) percent predicted (%p) in COPD patients and controls. Patients and methods Eighty-one smokers/ex-smokers (41 controls and 40 COPD) performed spirometry, body plethysmography, impulse oscillometry and single-breath helium dilution carbon monoxide diffusion at baseline, after salbutamol inhalation and then after an additional inhalation of ipratropium. Results Most pulmonary function parameters showed a linear increase in response to decreased FEV1%p. The subjects were divided into groups of FEV1%p <65 and >65, and the findings from continuous analysis were verified. The exceptions to this linear response were inspiratory capacity (IC), forced vital capacity (FVC), FEV1/FVC and expiratory resistance (Rex), which showed a segmented response relationship to FEV1%p. IC and FVC, with break points (BP) of 57 and 58 FEV1%p respectively, showed no response above, but an incresed slope below the BP. In addition, in patients with FEV1%p <65 and >65, response of FEV1%p did not correlate to response of volume parameters. Conclusion Response of several advanced lung function parameters differs depending on patients’ baseline FEV1%p, and specifically response of volume parameters is most pronounced in COPD patients with FEV1%p <65. Volume and resistance responses do not follow the flow response measured with FEV1 and may thus be used as a complement to FEV1 reversibility to identify flow, volume and resistance responders. PMID:27932874

  7. Two-Axis Acceleration of Functional Connectivity Magnetic Resonance Imaging by Parallel Excitation of Phase-Tagged Slices and Half k-Space Acceleration

    PubMed Central

    Jesmanowicz, Andrzej; Nencka, Andrew S.; Li, Shi-Jiang

    2011-01-01

    Abstract Whole brain functional connectivity magnetic resonance imaging requires acquisition of a time course of gradient-recalled (GR) volumetric images. A method is developed to accelerate this acquisition using GR echo-planar imaging and radio frequency (RF) slice phase tagging. For N-fold acceleration, a tailored RF pulse excites N slices using a uniform-field transmit coil. This pulse is the Fourier transform of the profile for the N slices with a predetermined RF phase tag on each slice. A multichannel RF receive coil is used for detection. For n slices, there are n/N groups of slices. Signal-averaged reference images are created for each slice within each slice group for each member of the coil array and used to separate overlapping images that are simultaneously received. The time-overhead for collection of reference images is small relative to the acquisition time of a complete volumetric time course. A least-squares singular value decomposition method allows image separation on a pixel-by-pixel basis. Twofold slice acceleration is demonstrated using an eight-channel RF receive coil, with application to resting-state functional magnetic resonance imaging in the human brain. Data from six subjects at 3 T are reported. The method has been extended to half k-space acquisition, which not only provides additional acceleration, but also facilitates slice separation because of increased signal intensity of the central lines of k-space coupled with reduced susceptibility effects. PMID:22432957

  8. Computational modeling of a forward lunge: towards a better understanding of the function of the cruciate ligaments.

    PubMed

    Alkjaer, Tine; Wieland, Maja R; Andersen, Michael S; Simonsen, Erik B; Rasmussen, John

    2012-12-01

    This study investigated the function of the cruciate ligaments during a forward lunge movement. The mechanical roles of the anterior and posterior cruciate ligament (ACL, PCL) during sagittal plane movements, such as forward lunging, are unclear. A forward lunge movement contains a knee joint flexion and extension that is controlled by the quadriceps muscle. The contraction of the quadriceps can cause anterior tibial translation, which may strain the ACL at knee joint positions close to full extension. However, recent findings suggest that it is the PCL rather than the ACL which is strained during forward lunging. Thus, the purpose of the present study was to establish a musculoskeletal model of the forward lunge to computationally investigate the complete mechanical force equilibrium of the tibia during the movement to examine the loading pattern of the cruciate ligaments. A healthy female was selected from a group of healthy subjects who all performed a forward lunge on a force platform, targeting a knee flexion angle of 90°. Skin-markers were placed on anatomical landmarks on the subject and the movement was recorded by five video cameras. The three-dimensional kinematic data describing the forward lunge movement were extracted and used to develop a biomechanical model of the lunge movement. The model comprised two legs including femur, crus, rigid foot segments and the pelvis. Each leg had 35 independent muscle units, which were recruited according to a minimum fatigue criterion. This approach allowed a full understanding of the mechanical equilibrium of the knee joint, which revealed that the PCL had an important stabilizing role in the forward lunge movement. In contrast, the ACL did not have any significant mechanical function during the lunge movement. Furthermore, the results showed that m. gluteus maximus may play a role as a knee stabilizer in addition to the hamstring muscles.

  9. [The scintigraphic prediction of residual lung function after lobectomy in patients with bronchial carcinoma].

    PubMed

    Giordano, A; Calcagni, M L; Rossi, B; D'Ugo, D; Corbo, G M; Fumagalli, G; Valente, S; D'Andrea, G; Galli, G

    1995-04-01

    The scintigraphic prediction of residual pulmonary function after pneumonectomy has been validated in a number of studies while scintigraphy is not standardized in case of lobectomy. This study was aimed at investigating the accuracy of the scintigraphic prediction of post-lobectomy lung function using Wernly method. We examined 43 patients with bronchial carcinoma: 20 of them underwent pneumonectomy and 23 underwent lobectomy. The pulmonary function data (vital capacity, CV, and forced expiratory volume in one second, VEMS) predicted by quantitative lung scan were compared with those observed in the postoperative follow-up. A good correlation between predicted and observed data was obtained in both the pneumonectomized group (r = 0.77 and 0.78 for CV and VEMS, respectively; p < 0.005) and the lobectomized group (r = 0.74 and 0.79 for CV and VEMS, respectively: p < 0.005). It can be concluded that the method used for the scintigraphy prediction of post-lobectomy pulmonary function is as accurate as the post-pneumonectomy method and can be used reliably in the clinical practice.

  10. Characterization of lung inflammation and its impact on macrophage function in aging

    PubMed Central

    Canan, Cynthia H.; Gokhale, Nandan S.; Carruthers, Bridget; Lafuse, William P.; Schlesinger, Larry S.; Torrelles, Jordi B.; Turner, Joanne

    2014-01-01

    Systemic inflammation that occurs with increasing age (inflammaging) is thought to contribute to the increased susceptibility of the elderly to several disease states. The elderly are at significant risk for developing pulmonary disorders and infectious diseases, but the contribution of inflammation in the pulmonary environment has received little attention. In this study, we demonstrate that the lungs of old mice have elevated levels of proinflammatory cytokines and a resident population of highly activated pulmonary macrophages that are refractory to further activation by IFN-γ. The impact of this inflammatory state on macrophage function was determined in vitro in response to infection with M.tb. Macrophages from the lungs of old mice secreted more proinflammatory cytokines in response to M.tb infection than similar cells from young mice and also demonstrated enhanced M.tb uptake and P-L fusion. Supplementation of mouse chow with the NSAID ibuprofen led to a reversal of lung and macrophage inflammatory signatures. These data indicate that the pulmonary environment becomes inflammatory with increasing age and that this inflammatory environment can be reversed with ibuprofen. PMID:24935957

  11. Gain of Nrf2 function in non-small-cell lung cancer cells confers radioresistance.

    PubMed

    Singh, Anju; Bodas, Manish; Wakabayashi, Nobunao; Bunz, Fred; Biswal, Shyam

    2010-12-01

    Nuclear factor erythroid-2 related factor 2 (Nrf2), a redox-sensitive transcription factor, regulates the expression of antioxidant enzymes and several anti-apoptotic proteins, which confer cytoprotection against oxidative stress and apoptosis. Constitutive activation of Nrf2 in lung cancer cells promotes tumorigenicity and contributes to chemoresistance by upregulation of glutathione, thioredoxin, and the drug efflux pathways involved in detoxification of electrophiles and broad spectrum of drugs. In this study, we show that RNAi-mediated lowering of Nrf2 levels in non-small-cell lung cancer (NSCLC) cell lines (A549 and H460) led to a dramatic increase in endogenous reactive oxygen species (ROS) levels. Similarly, γ-irradiation-induced formation of protein carbonyls were significantly higher in Nrf2-depleted lung cancer cells, suggesting increased lethality of ionizing radiation in the absence of Nrf2. Radiation-induced protein oxidation in Nrf2shRNA cells correlated with reduced survival as measured by clonogenic assay. Radiation-induced cell death was abrogated by pretreatment with antioxidants such as N-acetyl-L-cysteine, glutathione, and vitamin-E, highlighting the importance of antioxidants in conferring protection against radiation injury. Using genetically-modified gain and loss of function models of Nrf2, in mouse embryonic fibroblasts, we establish that constitutive activation of Nrf2 protects against ionizing radiation toxicity and confers radioresistance. Thus, targeting Nrf2 activity in radioresistant tumors could be a promising strategy to circumvent radioresistance.

  12. Gain of Nrf2 Function in Non-Small-Cell Lung Cancer Cells Confers Radioresistance

    PubMed Central

    Singh, Anju; Bodas, Manish; Wakabayashi, Nobunao; Bunz, Fred

    2010-01-01

    Abstract Nuclear factor erythroid-2 related factor 2 (Nrf2), a redox-sensitive transcription factor, regulates the expression of antioxidant enzymes and several anti-apoptotic proteins, which confer cytoprotection against oxidative stress and apoptosis. Constitutive activation of Nrf2 in lung cancer cells promotes tumorigenicity and contributes to chemoresistance by upregulation of glutathione, thioredoxin, and the drug efflux pathways involved in detoxification of electrophiles and broad spectrum of drugs. In this study, we show that RNAi-mediated lowering of Nrf2 levels in non-small-cell lung cancer (NSCLC) cell lines (A549 and H460) led to a dramatic increase in endogenous reactive oxygen species (ROS) levels. Similarly, γ-irradiation-induced formation of protein carbonyls were significantly higher in Nrf2-depleted lung cancer cells, suggesting increased lethality of ionizing radiation in the absence of Nrf2. Radiation-induced protein oxidation in Nrf2shRNA cells correlated with reduced survival as measured by clonogenic assay. Radiation-induced cell death was abrogated by pretreatment with antioxidants such as N-acetyl-L-cysteine, glutathione, and vitamin-E, highlighting the importance of antioxidants in conferring protection against radiation injury. Using genetically-modified gain and loss of function models of Nrf2, in mouse embryonic fibroblasts, we establish that constitutive activation of Nrf2 protects against ionizing radiation toxicity and confers radioresistance. Thus, targeting Nrf2 activity in radioresistant tumors could be a promising strategy to circumvent radioresistance. Antioxid. Redox Signal. 13, 1627–1637. PMID:20446773

  13. Analysis of tidal breathing flow volume loops for automated lung-function diagnosis in infants.

    PubMed

    Leonhardt, Steffen; Ahrens, Peter; Kecman, Vojislav

    2010-08-01

    Lung-function analysis in the age group below 5 years has not yet found its way into clinical routine. One possible candidate for routine lung testing in this age group is the analysis of tidal breathing flow-volume (TBFV) loops, a technique that has not yet proven to be capable of detecting obstructive and other lung disorders at an early stage. We present a new set of mathematical features useful to analyze TBFV loops. These new features attempt to describe more complex properties of the loops, thus imitating medical judgment of the curves (e.g., "round," "triangular," etc.) in a "linguistic" manner. Furthermore, we introduce support vector machines (SVMs) as a method for automated classification of diseases. In a retrospective clinical trial on 195 spontaneously breathing infants aged 3 to 24 months, the discriminant power of individual features and the overall diagnostic performance of SVMs is investigated and compared with the results obtained with traditional Bayes' classifiers. We demonstrate that the proposed new features perform better in all examined disease groups and that depending on the disease, the classification error can be reduced by up to 50%. We conclude that TBFV loops may have a much stronger discriminant power than previously thought.

  14. Functional invariant NKT cells in pig lungs regulate the airway hyperreactivity: a potential animal model.

    PubMed

    Renukaradhya, Gourapura J; Manickam, Cordelia; Khatri, Mahesh; Rauf, Abdul; Li, Xiangming; Tsuji, Moriya; Rajashekara, Gireesh; Dwivedi, Varun

    2011-04-01

    Important roles played by invariant natural killer T (iNKT) cells in asthma pathogenesis have been demonstrated. We identified functional iNKT cells and CD1d molecules in pig lungs. Pig iNKT cells cultured in the presence of α-GalCer proliferated and secreted Th1 and Th2 cytokines. Like in other animal models, direct activation of pig lung iNKT cells using α-GalCer resulted in acute airway hyperreactivity (AHR). Clinically, acute AHR-induced pigs had increased respiratory rate, enhanced mucus secretion in the airways, fever, etc. In addition, we observed petechial hemorrhages, infiltration of CD4(+) cells, and increased Th2 cytokines in AHR-induced pig lungs. Ex vivo proliferated iNKT cells of asthma induced pigs in the presence of C-glycoside analogs of α-GalCer had predominant Th2 phenotype and secreted more of Th2 cytokine, IL-4. Thus, baby pigs may serve as a useful animal model to study iNKT cell-mediated AHR caused by various environmental and microbial CD1d-specific glycolipid antigens.

  15. Effect of plasma exchange in accelerating natalizumab clearance and restoring leukocyte function

    PubMed Central

    Khatri, B O.; Man, S; Giovannoni, G; Koo, A P.; Lee, J-C; Tucky, B; Lynn, F; Jurgensen, S; Woodworth, J; Goelz, S; Duda, P W.; Panzara, M A.; Ransohoff, R M.; Fox, R J.

    2009-01-01

    Background: Accelerating the clearance of therapeutic monoclonal antibodies (mAbs) from the body may be useful to address uncommon but serious complications from treatment, such as progressive multifocal leukoencephalopathy (PML). Treatment of PML requires immune reconstitution. Plasma exchange (PLEX) may accelerate mAb clearance, restoring the function of inhibited proteins and increasing the number or function of leukocytes entering the CNS. We evaluated the efficacy of PLEX in accelerating natalizumab (a therapy for multiple sclerosis [MS] and Crohn disease) clearance and α4-integrin desaturation. Restoration of leukocyte transmigratory capacity was evaluated using an in vitro blood–brain barrier (ivBBB). Methods: Twelve patients with MS receiving natalizumab underwent three 1.5-volume PLEX sessions over 5 or 8 days. Natalizumab concentrations and α4-integrin saturation were assessed daily throughout PLEX and three times over the subsequent 2 weeks, comparing results with the same patients the previous month. Peripheral blood mononuclear cell (PBMC) migration (induced by the chemokine CCL2) across an ivBBB was assessed in a subset of six patients with and without PLEX. Results: Serum natalizumab concentrations were reduced by a mean of 92% from baseline to 1 week after three PLEX sessions (p < 0.001). Although average α4-integrin saturation was not reduced after PLEX, it was reduced to less than 50% when natalizumab concentrations were below 1 μg/mL. PBMC transmigratory capacity increased 2.2-fold after PLEX (p < 0.006). Conclusions: Plasma exchange (PLEX) accelerated clearance of natalizumab, and at natalizumab concentrations below 1 μg/mL, desaturation of α4-integrin was observed. Also, CCL2-induced leukocyte transmigration across an in vitro blood–brain barrier was increased after PLEX. Therefore, PLEX may be effective in restoring immune effector function in natalizumab-treated patients. GLOSSARY AE = adverse event; BBB = blood–brain barrier; BW

  16. Accuracy of forced oscillation technique to assess lung function in geriatric COPD population

    PubMed Central

    Tse, Hoi Nam; Tseng, Cee Zhung Steven; Wong, King Ying; Yee, Kwok Sang; Ng, Lai Yun

    2016-01-01

    Introduction Performing lung function test in geriatric patients has never been an easy task. With well-established evidence indicating impaired small airway function and air trapping in patients with geriatric COPD, utilizing forced oscillation technique (FOT) as a supplementary tool may aid in the assessment of lung function in this population. Aims To study the use of FOT in the assessment of airflow limitation and air trapping in geriatric COPD patients. Study design A cross-sectional study in a public hospital in Hong Kong. ClinicalTrials.gov ID: NCT01553812. Methods Geriatric patients who had spirometry-diagnosed COPD were recruited, with both FOT and plethysmography performed. “Resistance” and “reactance” FOT parameters were compared to plethysmography for the assessment of air trapping and airflow limitation. Results In total, 158 COPD subjects with a mean age of 71.9±0.7 years and percentage of forced expiratory volume in 1 second of 53.4±1.7 L were recruited. FOT values had a good correlation (r=0.4–0.7) to spirometric data. In general, X values (reactance) were better than R values (resistance), showing a higher correlation with spirometric data in airflow limitation (r=0.07–0.49 vs 0.61–0.67), small airway (r=0.05–0.48 vs 0.56–0.65), and lung volume (r=0.12–0.29 vs 0.43–0.49). In addition, resonance frequency (Fres) and frequency dependence (FDep) could well identify the severe type (percentage of forced expiratory volume in 1 second <50%) of COPD with high sensitivity (0.76, 0.71) and specificity (0.72, 0.64) (area under the curve: 0.8 and 0.77, respectively). Moreover, X values could stratify different severities of air trapping, while R values could not. Conclusion FOT may act as a simple and accurate tool in the assessment of severity of airflow limitation, small and central airway function, and air trapping in patients with geriatric COPD who have difficulties performing conventional lung function test. Moreover, reactance

  17. Lung surfactant: Function and composition in the context of development and respiratory physiology.

    PubMed

    Bernhard, Wolfgang

    2016-11-01

    Lung surfactant is a complex with a unique phospholipid and protein composition. Its specific function is to reduce surface tension at the pulmonary air-liquid interface. The underlying Young-Laplace equation, applying to the surface of any geometrical structure, is the more important the smaller its radii are. It therefore applies to the alveoli and bronchioli of mature lungs, as well as to the tubules and saccules of immature lungs. Surfactant comprises 80% phosphatidylcholine (PC), of which dipalmitoyl-PC, palmitoyl-myristoyl-PC and palmitoyl-palmitoleoyl-PC together are 75%. Anionic phosphatidylglycerol and cholesterol are about 10% each, whereas surfactant proteins SP-A to -D comprise 2-5%. Maturation of the surfactant system is not essentially due to increased synthesis but to decreased turnover of specific components. Molecular differences correlate with resting respiratory rate (RR), where PC16:0/16:0 is the lower the higher RR is. PC16:0/14:0 is increased during alveolar formation, and decreases immune reactions that might impair alveolar development. In rigid bird lungs, with air-capillaries rather than alveoli, and no surface area changes during the respiratory cycle, PC16:0/16:0 is highest and PC16:0/14:0 absent. As there is no need for a surface-associated surfactant reservoir, SP-C is absent in birds as well. Airflow is lowest and particle sedimentation highest in the extrapulmonary air-sacs, rather than in the gas-exchange area. Consequently, SP-A and -D for particle opsonization are absent in bird surfactant. In essence, comparative analysis is consistent with the concept that surfactant is adapted to the physiologic needs of a given vertebrate species at a given developmental stage.

  18. Loss of Rab27 function results in abnormal lung epithelium structure in mice.

    PubMed

    Bolasco, Giulia; Tracey-White, Dhani C; Tolmachova, Tanya; Thorley, Andrew J; Tetley, Teresa D; Seabra, Miguel C; Hume, Alistair N

    2011-03-01

    Rab27 small GTPases regulate secretion and movement of lysosome-related organelles such as T cell cytolytic granules and platelet-dense granules. Previous studies indicated that Rab27a and Rab27b are expressed in the murine lung suggesting that they regulate secretory processes in the lung. Consistent with those studies, we found that Rab27a and Rab27b are expressed in cell types that contain secretory granules: alveolar epithelial type II (AEII) and Clara cells. We then used Rab27a/Rab27b double knockout (DKO) mice to examine the functional consequence of loss of Rab27 proteins in the murine lung. Light and electron microscopy revealed a number of morphological changes in lungs from DKO mice when compared with those in control animals. In aged DKO mice we observed atrophy of the bronchiolar and alveolar epithelium with reduction of cells numbers, thinning of the bronchiolar epithelium and alveolar walls, and enlargement of alveolar airspaces. In these samples we also observed increased numbers of activated foamy alveolar macrophages and granulocyte containing infiltrates together with reduction in the numbers of Clara cells and AEII cells compared with control. At the ultrastructural level we observed accumulation of cytoplasmic membranes and vesicles in Clara cells. Meanwhile, AEII cells in DKO accumulated large mature lamellar bodies and lacked immature/precursor lamellar bodies. We hypothesize that the morphological changes observed at the ultrastructural level in DKO samples result from secretory defects in AEII and Clara cells and that over time these defects lead to atrophy of the epithelium.

  19. Automated ARGET ATRP Accelerates Catalyst Optimization for the Synthesis of Thiol-Functionalized Polymers.

    PubMed

    Siegwart, Daniel J; Leiendecker, Matthias; Langer, Robert; Anderson, Daniel G

    2012-02-14

    Conventional synthesis of polymers by ATRP is relatively low throughput, involving iterative optimization of conditions in an inert atmosphere. Automated, high-throughput controlled radical polymerization was developed to accelerate catalyst optimization and production of disulfide-functionalized polymers without the need of an inert gas. Using ARGET ATRP, polymerization conditions were rapidly identified for eight different monomers, including the first ARGET ATRP of 2-(diethylamino)ethyl methacrylate and di(ethylene glycol) methyl ether methacrylate. In addition, butyl acrylate, oligo(ethylene glycol) methacrylate 300 and 475, 2-(dimethylamino)ethyl methacrylate, styrene, and methyl methacrylate were polymerized using bis(2-hydroxyethyl) disulfide bis(2-bromo-2-methylpropionate) as the initiator, tris(2-pyridylmethyl)amine as the ligand, and tin(II) 2-ethylhexanoate as the reducing agent. The catalyst and reducing agent concentration was optimized specifically for each monomer, and then a library of polymers was synthesized systematically using the optimized conditions. The disulfide-functionalized chains could be cleaved to two thiol-terminated chains upon exposure to dithiothreitol, which may have utility for the synthesis of polymer bioconjugates. Finally, we demonstrated that these new conditions translated perfectly to conventional batch polymerization. We believe the methods developed here may prove generally useful to accelerate the systematic optimization of a variety of chemical reactions and polymerizations.

  20. Triboelectric Nanogenerator Accelerates Highly Efficient Nonviral Direct Conversion and In Vivo Reprogramming of Fibroblasts to Functional Neuronal Cells.

    PubMed

    Jin, Yoonhee; Seo, Jungmok; Lee, Jung Seung; Shin, Sera; Park, Hyun-Ji; Min, Sungjin; Cheong, Eunji; Lee, Taeyoon; Cho, Seung-Woo

    2016-09-01

    Triboelectric nanogenerators (TENGs) can be an effective cell reprogramming platform for producing functional neuronal cells for therapeutic applications. Triboelectric stimulation accelerates nonviral direct conversion of functional induced neuronal cells from fibroblasts, increases the conversion efficiency, and induces highly matured neuronal phenotypes with improved electrophysiological functionalities. TENG devices may also be used for biomedical in vivo reprogramming.

  1. Assessment of Regional Lung Function with Multivolume 1H MR Imaging in Health and Obstructive Lung Disease: Comparison with 3He MR Imaging

    PubMed Central

    Quirk, James D.; Yablonskiy, Dmitriy A.; Castro, Mario; Aliverti, Andrea; Woods, Jason C.

    2014-01-01

    Purpose To introduce a method based on multivolume proton (hydrogen [1H]) magnetic resonance (MR) imaging for the regional assessment of lung ventilatory function, investigating its use in healthy volunteers and patients with obstructive lung disease and comparing the outcome with the outcome of the research standard helium 3 (3He) MR imaging. Materials and Methods The institutional review board approved the HIPAA-compliant protocol, and informed written consent was obtained from each subject. Twenty-six subjects, including healthy volunteers (n = 6) and patients with severe asthma (n = 11) and mild (n = 6) and severe (n = 3) emphysema, were imaged with a 1.5-T whole-body MR unit at four lung volumes (residual volume [RVresidual volume], functional residual capacity [FRCfunctional residual capacity], 1 L above FRCfunctional residual capacity [FRC+1 L1 L above FRC], total lung capacity [TLCtotal lung capacity]) with breath holds of 10–11 seconds, by using volumetric interpolated breath-hold examination. Each pair of volumes were registered, resulting in maps of 1H signal change between the two lung volumes. 3He MR imaging was performed at FRC+1 L1 L above FRC by using a two-dimensional gradient-echo sequence. 1H signal change and 3He signal were measured and compared in corresponding regions of interest selected in ventral, intermediate, and dorsal areas. Results In all volunteers and patients combined, proton signal difference between TLCtotal lung capacity and RVresidual volume correlated positively with 3He signal (correlation coefficient R2 = 0.64, P < .001). Lower (P < .001) but positive correlation results from 1H signal difference between FRCfunctional residual capacity and FRC+1 L1 L above FRC (R2 = 0.44, P < .001). In healthy volunteers, 1H signal changes show a higher median and interquartile range compared with patients with obstructive disease and significant differences between nondependent and dependent regions. Conclusion Findings in this study

  2. The association between ambient temperature and children's lung function in Baotou, China

    NASA Astrophysics Data System (ADS)

    Li, Shanshan; Guo, Yuming; Williams, Gail; Baker, Peter; Ye, Xiaofang; Madaniyazi, Lina; Kim, Dae-Seon; Pan, Xiaochuan

    2015-07-01

    The objective of this study is to examine the association between ambient temperature and children's lung function in Baotou, China. We recruited 315 children (8-12 years) from Baotou, China in the spring of 2004, 2005, and 2006. They performed three successive forced expiratory measurements three times daily (morning, noon, and evening) for about 5 weeks. The highest peak expiratory flow (PEF) was recorded for each session. Daily data on ambient temperature, relative humidity, and air pollution were monitored during the same period. Mixed models with a distributed lag structure were used to examine the effects of temperature on lung function while adjusting for individual characteristics and environmental factors. Low temperatures were significantly associated with decreases in PEF. The effects lasted for lag 0-2 days. For all participants, the cumulative effect estimates (lag 0-2 days) were -1.44 (-1.93, -0.94) L/min, -1.39 (-1.92, -0.86) L/min, -1.40 (-1.97, -0.82) L/min, and -1.28 (-1.69, -0.88) L/min for morning, noon, evening, and daily mean PEF, respectively, associated with 1 °C decrease in daily mean temperature. Generally, the effects of temperature were slightly stronger in boys than in girls for noon, evening, and daily mean PEF, while the effects were stronger in girls for morning PEF. PM2.5 had joint effects with temperature on children's PEF. Higher PM2.5 increased the impacts of low temperature. Low ambient temperatures are associated with lower lung function in children in Baotou, China. Preventive health policies will be required for protecting children from the cold weather.

  3. Radiological progression and lung function in silicosis: a ten year follow up study.

    PubMed Central

    Ng, T P; Chan, S L; Lam, K P

    1987-01-01

    Chest radiographs and spirometric tests were performed on 81 patients who had silicosis from two granite quarries in 1975, 73 of whom were followed up for two to 10 (mean 7.2) years. Each patient's initial and most recent chest radiographs were assessed independently by three experienced readers, and the yearly declines in forced expiratory volume in one second and forced vital capacity were estimated from two to four (mean 3.45) serial spirometric readings. Estimates of individual dust exposure were based on extensive historical data on hygiene. All but 11 patients were no longer exposed to dust by the start of follow up, but 24 (45%) of 53 patients who had simple silicosis and 11 (55%) of 20 who had the complicated disease showed radiological evidence of disease progression. In patients who had simple silicosis and showed no radiological progression the yearly declines in forced expiratory volume in one second and forced vital capacity were modest (64 ml/year and 59 ml/year, respectively), whereas significantly greater declines in lung function were seen in those who showed radiological evidence of progression (97 ml/year and 95 ml/year, respectively). In addition to radiological progression the previous average dust concentration to which patients had been exposed also influenced declines in both forced expiratory volume in one second and forced vital capacity after allowing for the effects of age, smoking, duration of exposure, history of tuberculosis, initial state of disease, and baseline lung function. The probability of radiological progression was most strongly influenced by the average dust concentration previously exposed to. The progression of simple silicosis is thus accompanied by appreciable declines in lung function and is strongly affected by previous levels of exposure to dust. PMID:3115361

  4. Effects on symptoms and lung function in humans experimentally exposed to diesel exhaust.

    PubMed Central

    Rudell, B; Ledin, M C; Hammarström, U; Stjernberg, N; Lundbäck, B; Sandström, T

    1996-01-01

    OBJECTIVES: Diesel exhaust is a common air pollutant made up of several gases, hydrocarbons, and particles. An experimental study was carried out which was designed to evaluate if a particle trap on the tail pipe of an idling diesel engine would reduce effects on symptoms and lung function caused by the diesel exhaust, compared with exposure to unfiltered exhaust. METHODS: Twelve healthy non-smoking volunteers (aged 20-37) were investigated in an exposure chamber for one hour during light work on a bicycle ergometer at 75 W. Each subject underwent three separate double blind exposures in a randomised sequence: to air and to diesel exhaust with the particle trap at the tail pipe and to unfiltered diesel exhaust. Symptoms were recorded according to the Borg scale before, every 10 minutes during, and 30 minutes after the exposure. Lung function was measured with a computerised whole body plethysmograph. RESULTS: The ceramic wall flow particle trap reduced the number of particles by 46%, whereas other compounds were relatively constant. It was shown that the most prominent symptoms during exposure to diesel exhaust were irritation of the eyes and nose and an unpleasant smell increasing during exposure. Both airway resistance (R(aw)) and specific airway resistance (SR(aw)) increased significantly during the exposures to diesel exhaust. Despite the 46% reduction in particle numbers by the trap effects on symptoms and lung function were not significantly attenuated. CONCLUSION: Exposure to diesel exhaust caused symptoms and bronchoconstriction which were not significantly reduced by a particle trap. PMID:8943829

  5. Elemental carbon exposure and lung function in school children from Mexico City.

    PubMed

    Barraza-Villarreal, A; Escamilla-Nuñez, M C; Hernández-Cadena, L; Texcalac-Sangrador, J L; Sienra-Monge, J J; Del Río-Navarro, B E; Cortez-Lugo, M; Sly, P D; Romieu, I

    2011-09-01

    Though exposure to air pollution has a detrimental effect on respiratory health, few studies have examined the association between elemental carbon exposure and lung function among schoolchildren. The aim of the present study was to present the association between short-term elemental carbon exposure and lung function in schoolchildren from Mexico City. 55 asthmatic and 40 non-asthmatic children were followed for an average of 22 weeks. A spirometry test was performed every 15 days during follow-up. Portable air samplers collected particulate matter onto Teflon filters. Gravimetric analysis was conducted and elemental carbon was quantified using transmission densitometry. The association between the main variables was analysed using linear mixed effects models. The mean ± sd of elemental carbon light absorption was 92.7 ± 54.7 Mm(-1). An increase of one interquartile range in the 24-h average of elemental carbon (100.93 Mm(-1)) was associated with a significant negative impact on forced expiratory volume in 1 s (FEV(1)) (-62.0 (95% CI -123.3- -1.2) mL) and forced expiratory flow at 25-75% of forced vital capacity (FVC) (FEF(25-75%)) (-111 (95% CI -228.3- -4.1) mL) among asthmatic children, equal to 3.3% and 5.5%, respectively; and on FEV(1) (-95.0 (95% CI -182.3- -8.5) mL) and FVC (-105.0 (95% CI -197.0- -13.7) mL) among non-asthmatic children. Exposure to elemental carbon resulted in an important negative effect on lung function in atopic schoolchildren, regardless of asthma status.

  6. A systematic review of the association between pleural plaques and changes in lung function

    PubMed Central

    Kopylev, Leonid; Christensen, Krista Yorita; Brown, James S; Cooper, Glinda S

    2015-01-01

    Objectives To conduct a systematic review of changes in lung function in relation to presence of pleural plaques in asbestos-exposed populations. Methods Database searches of PubMed and Web of Science were supplemented by review of papers’ reference lists and journals’ tables of contents. Methodological features (eg, consideration of potential confounding by smoking) of identified articles were reviewed by ≥two reviewers. Meta-analyses of 20 studies estimated a summary effect of the decrements in per cent predicted (%pred) forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) associated with presence of pleural plaques. Results Among asbestos-exposed workers, the presence of pleural plaques was associated with statistically significant decrements in FVC (4.09%pred, 95% CI 2.31 to 5.86) and FEV1 (1.99%pred, 95% CI 0.22 to 3.77). Effects of similar magnitude were seen when stratifying by imaging type (X-ray or high-resolution CT) and when excluding studies with potential methodological limitations. Undetected asbestosis was considered as an unlikely explanation of the observed decrements. Several studies provided evidence of an association between size of pleural plaques and degree of pulmonary decrease, and presence of pleural plaques and increased rate or degree of pulmonary impairment. Conclusions The presence of pleural plaques is associated with a small, but statistically significant mean difference in FVC and FEV1 in comparison to asbestos-exposed individuals without plaques or other abnormalities. From a public health perspective, small group mean decrements in lung function coupled with an increased rate of decline in lung function of the exposed population may be consequential. PMID:25504898

  7. The alveolitis of pulmonary sarcoidosis. Evaluation of natural history and alveolitis-dependent changes in lung function

    SciTech Connect

    Keogh, B.A.; Hunninghake, G.W.; Line, B.R.; Crystal, R.G.

    1983-08-01

    Current concepts of the pathogenesis of pulmonary sarcoidosis suggest that a mononuclear cell alveolitis, comprised of activated T-lymphocytes and activated alveolar macrophages, precedes and modulates the formation of granuloma and fibrosis. To evaluate the natural history of this alveolitis and determine the relationship it has to subsequent changes in lung function, 19 untreated patients with pulmonary sarcoidosis without extrapulmonary manifestations were studied with bronchoalveolar lavage, /sup 67/Ga scanning, and pulmonary function tests to evaluate lung T-cells, lung alveolar macrophages, and lung function, respectively. In patients with sarcoidosis, low intensity alveolitis (lung T-cells less than or equal to 28% of all lung effector cells and/or /sup 67/Ga scan negative) was much more common (80% of all observations) than high intensity alveolitis (lung T-cells greater than 28% and /sup 67/Ga scan positive, 20% of all observations). Conventional clinical, roentgenographic, or physiologic studies could not predict the alveolitis status. Interestingly, of the 51 alveolitis evaluations in the 19 patients, there were 24 occurrences (47%) where the alveolitis was ''split,'' i.e., /sup 67/Ga scans positive and T-cells low (39%) or /sup 67/Ga negative and T-cells high (8%). Most untreated patients with sarcoidosis without extrapulmonary symptoms may have some inflammatory processes ongoing in their alveolar structures. Overall, whenever a high intensity alveolitis episode occurred, it was followed by deterioration over the next 6 months in at least one lung function parameter. A low intensity alveolitis episode was followed by functional deterioration only 8% of the time. The alveolitis parameters (lavage and /sup 67/Ga scanning) clearly predicted prognosis. These observations should prove useful in understanding the natural history of pulmonary sarcoidosis, in staging patients with this disease, and in making rational therapy decisions.

  8. Improved Classification of Lung Cancer Using Radial Basis Function Neural Network with Affine Transforms of Voss Representation

    PubMed Central

    Adetiba, Emmanuel; Olugbara, Oludayo O.

    2015-01-01

    Lung cancer is one of the diseases responsible for a large number of cancer related death cases worldwide. The recommended standard for screening and early detection of lung cancer is the low dose computed tomography. However, many patients diagnosed die within one year, which makes it essential to find alternative approaches for screening and early detection of lung cancer. We present computational methods that can be implemented in a functional multi-genomic system for classification, screening and early detection of lung cancer victims. Samples of top ten biomarker genes previously reported to have the highest frequency of lung cancer mutations and sequences of normal biomarker genes were respectively collected from the COSMIC and NCBI databases to validate the computational methods. Experiments were performed based on the combinations of Z-curve and tetrahedron affine transforms, Histogram of Oriented Gradient (HOG), Multilayer perceptron and Gaussian Radial Basis Function (RBF) neural networks to obtain an appropriate combination of computational methods to achieve improved classification of lung cancer biomarker genes. Results show that a combination of affine transforms of Voss representation, HOG genomic features and Gaussian RBF neural network perceptibly improves classification accuracy, specificity and sensitivity of lung cancer biomarker genes as well as achieving low mean square error. PMID:26625358

  9. Lung function in North American Indian children: reference standards for spirometry, maximal expiratory flow volume curves, and peak expiratory flow.

    PubMed

    Wall, M A; Olson, D; Bonn, B A; Creelman, T; Buist, A S

    1982-02-01

    Reference standards of lung function was determined in 176 healthy North American Indian children (94 girls, 82 boys) 7 to 18 yr of age. Spirometry, maximal expiratory flow volume curves, and peak expiratory flow rate were measured using techniques and equipment recommended by the American Thoracic Society. Standing height was found to be an accurate predictor of lung function, and prediction equations for each lung function variable are presented using standing height as the independent variable. Lung volumes and expiratory flow rates in North American Indian children were similar to those previously reported for white and Mexican-American children but were greater than those in black children. In both boys and girls, lung function increased in a curvilinear fashion. Volume-adjusted maximal expiratory flow rates after expiring 50 or 75% of FVC tended to decrease in both sexes as age and height increased. Our maximal expiratory flow volume curve data suggest that as North American Indian children grow, lung volume increases at a slightly faster rate than airway size does.

  10. The Lung Function Impairment in Non-Atopic Patients With Chronic Rhinosinusitis and Its Correlation Analysis

    PubMed Central

    Zhang, Linghao; Zhang, Lu; Zhang, Chun-Hong; Fang, Xiao-Bi; Huang, Zhen-Xiao; Shi, Qing-Yuan; Wu, Li-Ping; Wu, Peng; Wang, Zhen-Zhen; Liao, Zhi-Su

    2016-01-01

    Objectives Chronic rhinosinusitis (CRS) is common disease in otorhinolaryngology and will lead to lower airway abnormality. However, the only lung function in CRS patients and associated factors have not been much studied. Methods One hundred patients with CRS with nasal polyps (CRSwNP group), 40 patients with CRS without nasal polyps (CRSsNP group), and 100 patients without CRS were enrolled. The difference in lung function was compared. Meanwhile, CRSwNP and CRSsNP group were required to undergo a bronchial provocation or dilation test. Additionally, subjective and objective outcomes were measured by the visual analogue scale (VAS), 20-item Sino-Nasal Outcome Test (SNOT-20), Lund-Mackay score, Lund-Kennedy endoscopic score. The correlation and regression methods were used to analyze the relationship between their lung function and the above parameters. Results The forced expiratory volume in 1 second (FEV1) and forced expiratory flow between 25% and 75% of forced vital capacity (FEF25-75) of CRSwNP group were significantly lower than other groups (P<0.05). On peak expiratory flow, there was no difference between three groups. In CRSwNP group, FEV1 was negatively correlated with peripheral blood eosinophil count (PBEC) and duration of disease (r=–0.348, P=0.013 and r=–0.344, P=0.014, respectively), FEF25-75 negatively with VAS, SNOT-20 (r=–0.490, P=0.028 and r=–0.478, P=0.033, respectively) in CRSsNP group. The incidence of positive bronchial provocation and dilation test was lower in CRSwNP group (10% and 0%, respectively), with both 0% in CRSsNP group. The multiple linear regression analysis indicated that change ratio of FEV1 before and after bronchial provocation or dilation test were correlated with PBEC in CRSwNP group (β=0.403, P=0.006). Conclusion CRS leading to impaired maximum ventilation and small airway is associated with the existence of nasal polyp. Lung function impairments can be reflected by PBEC, duration, VAS, and SNOT-20. In CRSw

  11. [Perioperative Pulmonary Rehabilitation for Lung Cancer Surgeries in Patients with Poor Pulmonary Function].

    PubMed

    Sano, Yuko

    2016-01-01

    To properly perform preoperative pulmonary rehabilitation is important for lung cancer surgeries in patients with poor pulmonary function such as severe chronic obstructive pulmonary disease( COPD) to prevent postoperative complications. Those programs include exercise training, pursed-lip breathing technique, activities of dairy living training and facilitating physical activities, all which are almost same as those for patients with stable COPD. Pedometer is a useful tool to lead patient's physical activities. Postoperative therapeutic programs are also important, which includes early mobilization, nutritional support, and so on.

  12. Low levels of air pollution induce changes of lung function in a panel of schoolchildren.

    PubMed

    Moshammer, H; Hutter, H-P; Hauck, H; Neuberger, M

    2006-06-01

    In search of sensitive screening parameters for assessing acute effects of ambient air pollutants in young schoolchildren, the impact of 8-h average air pollution before lung function testing was investigated by oscillatory measurements of resistance and spirometry with flow-volume loops. At a central elementary school in Linz, the capital of Upper Austria, 163 children aged 7-10 yrs underwent repeated examinations at the same time of day during 1 school year, yielding a total of 11-12 lung function tests per child. Associations to mass concentrations of particulate matter and nitrogen dioxide (NO(2)) measured continuously at a nearby monitoring station were tested, applying the Generalised Estimating Equations model. Reductions per 10 microg.m(-3) (both for particles and for NO(2)) were in the magnitude of 1% for most lung function parameters. The most sensitive indicator for acute effects of combustion-related pollutants was a change in maximal expiratory flow in small airways. NO(2) at concentrations below current standards reduced (in the multipollutant model) the forced expiratory volume in one second by 1.01%, maximal instantaneous forced flow when 50% of the forced vital capacity remains to be exhaled (MEF(50%)) by 1.99% and MEF(25%) by 1.96%. Peripheral resistance increased by 1.03% per 10 microg.m(-3) of particulate matter with a 50% cut-off aerodynamic diameter of 2.5 mum (PM(2.5)). Resistance is less influenced by the child's cooperation and should be utilised more often in environmental epidemiology when screening for early signs of small airway dysfunction from urban air pollution, but cannot replace the measurement of MEF(50%) and MEF(25%). In the basic model, the reduction of these parameters per 10 microg.m(-3) was highest for NO(2), followed by PM(1), PM(2.5) and PM(10), while exposure to coarse dust (PM(10)-PM(2.5)) did not change end-expiratory flow significantly. All acute effects of urban air pollution found on the lung function of healthy

  13. Functional divergence and convergence between the transcript network and gene network in lung adenocarcinoma

    PubMed Central

    Hsu, Min-Kung; Pan, Chia-Lin; Chen, Feng-Chi

    2016-01-01

    Introduction Alternative RNA splicing is a critical regulatory mechanism during tumorigenesis. However, previous oncological studies mainly focused on the splicing of individual genes. Whether and how transcript isoforms are coordinated to affect cellular functions remain underexplored. Also of great interest is how the splicing regulome cooperates with the transcription regulome to facilitate tumorigenesis. The answers to these questions are of fundamental importance to cancer biology. Results Here, we report a comparative study between the transcript-based network (TN) and the gene-based network (GN) derived from the transcriptomes of paired tumor–normal tissues from 77 lung adenocarcinoma patients. We demonstrate that the two networks differ significantly from each other in terms of patient clustering and the number and functions of network modules. Interestingly, the majority (89.5%) of multi-transcript genes have their transcript isoforms distributed in at least two TN modules, suggesting regulatory and functional divergences between transcript isoforms. Furthermore, TN and GN modules share onlŷ50%–60% of their biological functions. TN thus appears to constitute a regulatory layer separate from GN. Nevertheless, our results indicate that functional convergence and divergence both occur between TN and GN, implying complex interactions between the two regulatory layers. Finally, we report that the expression profiles of module members in both TN and GN shift dramatically yet concordantly during tumorigenesis. The mechanisms underlying this coordinated shifting remain unclear yet are worth further explorations. Conclusion We show that in lung adenocarcinoma, transcript isoforms per se are coordinately regulated to conduct biological functions not conveyed by the network of genes. However, the two networks may interact closely with each other by sharing the same or related biological functions. Unraveling the effects and mechanisms of such interactions will

  14. [Effects of air pollution from coal combustion on lung function in children].

    PubMed

    Wang, Hanzhang; Zhao, Chihong; Gu, Heng; Cheng, Yibin

    2003-03-01

    In order to observe effects of air pollution from burning coal on children's health, Four hundred fifty junior schoolers selected from three survey sites in Taiyuan city with different degrees air pollution were investigated using questionnairing survey and the lung function were tested. The results showed that children's pulmonary function in survey site A is lower than site B, and site B is lower than site C. The prevalence of ventilation disfunction were correlated to the types of heating, the separation of kitchen and bedroom and the pollutants concentration with logistic model. Multiple linear regression analysis showed that compared with site C, FVC and FEF50 in site A decreased by 65.80 +/- 33.35 ml and 119.27 +/- 78.74) ml respectively and, in site B, decreased (57.28 +/- 31.22) ml and (114.29 +/- 58.80) ml respectively (Model 1). FVC and FEF50 decreased by 69.10(31.50 ml and (119.79 +/- 86.82) ml respectively with one unit increase of Ln (SO2) (Model 2). FVC and FEF50 decreased by 193.50 +/- 65.55 ml and 171.69 +/- 87.11 ml respectively with one unit increase of Ln(PM10) (Model 3). It can be concluded that the air pollution from coal consumption in Taiyuan city had impact on the children's lung function.

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

    SciTech Connect

    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.

  16. Lung function and heart disease in American Indian adults with high frequency of metabolic abnormalities (from the Strong Heart Study).

    PubMed

    Yeh, Fawn; Dixon, Anne E; Best, Lyle G; Marion, Susan M; Lee, Elisa T; Ali, Tauqeer; Yeh, Jeunliang; Rhoades, Everett R; Howard, Barbara V; Devereux, Richard B

    2014-07-15

    The associations of pulmonary function with cardiovascular disease (CVD) independent of diabetes mellitus (DM) and metabolic syndrome have not been examined in a population-based setting. We examined prevalence and incidence CVD in relation to lower pulmonary function in the Strong Heart Study second examination (1993 to 1995) in 352 CVD and 2,873 non-CVD adults free of overt lung disease (mean age 60 years). Lung function was assessed by standard spirometry. Participants with metabolic syndrome or DM with or without CVD had lower pulmonary function than participants without these conditions after adjustment for hypertension, age, gender, abdominal obesity, smoking, physical activity index, and study field center. CVD participants with DM had significantly lower forced vital capacity than participants with CVD alone. Significant associations were observed between reduced pulmonary function, preclinical CVD, and prevalent CVD after adjustment for multiple CVD risk factors. During follow-up (median 13.3 years), pulmonary function did not predict CVD incidence, it predicted CVD mortality. Among 3,225 participants, 412 (298 without baseline CVD) died from CVD by the end of 2008. In models adjusted for multiple CVD risk factors, DM, metabolic syndrome, and baseline CVD, compared with highest quartile of lung function, lower lung function predicted CVD mortality (relative risk up to 1.5, 95% confidence interval 1.1 to 2.0, p<0.05). In conclusion, a population with a high prevalence of DM and metabolic syndrome and lower lung function was independently associated with prevalent clinical and preclinical CVD, and its impairment predicted CVD mortality. Additional research is needed to identify mechanisms linking metabolic abnormalities, low lung function, and CVD.

  17. Unattenuated structural and biochemical alterations in the rat lung during functional adaptation to ozone

    SciTech Connect

    Tepper, J.S.; Costa, D.L.; Lehmann, J.R.; Weber, M.F.; Hatch, G.E. )

    1989-08-01

    Acute ozone (O{sub 3}) exposure in humans produces changes in pulmonary function that attenuate with repeated exposure. This phenomenon, termed adaptation, has been produced in unanesthetized rats. Rats exposed to O3 (0, 0.35, 0.5, or 1.0 ppm) for 2.25 h for 5 consecutive days showed an increased frequency of breathing and a decreased tidal volume on Days 1 and 2 of exposure at all O{sub 3} concentrations. However, by Day 5 these breathing responses to O{sub 3} were diminished in rats exposed to 0.35 and 0.5 ppm, but not in rats exposed to 1.0 ppm. In addition, a flow limitation in smaller airways was observed after the second day of exposure to 0.5 ppm O{sub 3} that initially attenuated and then disappeared by the fifth day of exposure. In contrast to these findings, a light microscopic examination of fixed lung tissue sections from rats exposed to 0.5 ppm indicated a 5-day progressive pattern of epithelial damage and inflammation in the terminal bronchiolar region. A sustained 37% increase in lavageable protein was also observed over the course of the 5-day exposure regimen to 0.5 ppm. Lung glutathione increased initially, but it was within the control range on Days 4 and 5. Lung ascorbate was significantly elevated above control levels on Days 3 and 5. These data suggest that attenuation of the pulmonary function response to O{sub 3} occurs in laboratory rats with repeated exposure while biochemical and morphologic aspects of the tissue response continue to progress.

  18. Effector genomics accelerates discovery and functional profiling of potato disease resistance and phytophthora infestans avirulence genes.

    PubMed

    Vleeshouwers, Vivianne G A A; Rietman, Hendrik; Krenek, Pavel; Champouret, Nicolas; Young, Carolyn; Oh, Sang-Keun; Wang, Miqia; Bouwmeester, Klaas; Vosman, Ben; Visser, Richard G F; Jacobsen, Evert; Govers, Francine; Kamoun, Sophien; Van der Vossen, Edwin A G

    2008-08-06

    Potato is the world's fourth largest food crop yet it continues to endure late blight, a devastating disease caused by the Irish famine pathogen Phytophthora infestans. Breeding broad-spectrum disease resistance (R) genes into potato (Solanum tuberosum) is the best strategy for genetically managing late blight but current approaches are slow and inefficient. We used a repertoire of effector genes predicted computationally from the P. infestans genome to accelerate the identification, functional characterization, and cloning of potentially broad-spectrum R genes. An initial set of 54 effectors containing a signal peptide and a RXLR motif was profiled for activation of innate immunity (avirulence or Avr activity) on wild Solanum species and tentative Avr candidates were identified. The RXLR effector family IpiO induced hypersensitive responses (HR) in S. stoloniferum, S. papita and the more distantly related S. bulbocastanum, the source of the R gene Rpi-blb1. Genetic studies with S. stoloniferum showed cosegregation of resistance to P. infestans and response to IpiO. Transient co-expression of IpiO with Rpi-blb1 in a heterologous Nicotiana benthamiana system identified IpiO as Avr-blb1. A candidate gene approach led to the rapid cloning of S. stoloniferum Rpi-sto1 and S. papita Rpi-pta1, which are functionally equivalent to Rpi-blb1. Our findings indicate that effector genomics enables discovery and functional profiling of late blight R genes and Avr genes at an unprecedented rate and promises to accelerate the engineering of late blight resistant potato varieties.

  19. Effector Genomics Accelerates Discovery and Functional Profiling of Potato Disease Resistance and Phytophthora Infestans Avirulence Genes

    PubMed Central

    Vleeshouwers, Vivianne G. A. A.; Rietman, Hendrik; Krenek, Pavel; Champouret, Nicolas; Young, Carolyn; Oh, Sang-Keun; Wang, Miqia; Bouwmeester, Klaas; Vosman, Ben; Visser, Richard G. F.; Jacobsen, Evert; Govers, Francine; Kamoun, Sophien; Van der Vossen, Edwin A. G.

    2008-01-01

    Potato is the world's fourth largest food crop yet it continues to endure late blight, a devastating disease caused by the Irish famine pathogen Phytophthora infestans. Breeding broad-spectrum disease resistance (R) genes into potato (Solanum tuberosum) is the best strategy for genetically managing late blight but current approaches are slow and inefficient. We used a repertoire of effector genes predicted computationally from the P. infestans genome to accelerate the identification, functional characterization, and cloning of potentially broad-spectrum R genes. An initial set of 54 effectors containing a signal peptide and a RXLR motif was profiled for activation of innate immunity (avirulence or Avr activity) on wild Solanum species and tentative Avr candidates were identified. The RXLR effector family IpiO induced hypersensitive responses (HR) in S. stoloniferum, S. papita and the more distantly related S. bulbocastanum, the source of the R gene Rpi-blb1. Genetic studies with S. stoloniferum showed cosegregation of resistance to P. infestans and response to IpiO. Transient co-expression of IpiO with Rpi-blb1 in a heterologous Nicotiana benthamiana system identified IpiO as Avr-blb1. A candidate gene approach led to the rapid cloning of S. stoloniferum Rpi-sto1 and S. papita Rpi-pta1, which are functionally equivalent to Rpi-blb1. Our findings indicate that effector genomics enables discovery and functional profiling of late blight R genes and Avr genes at an unprecedented rate and promises to accelerate the engineering of late blight resistant potato varieties. PMID:18682852

  20. Combined Effects of in Utero and Adolescent Tobacco Smoke Exposure on Lung Function in C57Bl/6J Mice

    PubMed Central

    Drummond, David; Baravalle-Einaudi, Mélissa; Lezmi, Guillaume; Vibhushan, Shamila; Franco-Montoya, Marie-Laure; Hadchouel, Alice; Boczkowski, Jorge; Delacourt, Christophe

    2016-01-01

    Background: Fetal determinants of airway function, such as in utero exposure to maternal cigarette smoke (CS), may create a predisposition to adult airflow obstruction and chronic obstructive pulmonary disease (COPD) in adulthood. It has been suggested that active smoking in adolescence and preexisting airflow obstruction have synergistic deleterious effects. Objective: We used a mouse model to investigate whether there is a synergistic effect of exposure to CS in utero and during adolescence on lung function. Methods: Female C57Bl/6J mice were exposed to CS or to filtered room air during pregnancy. Exposure to CS began 2 weeks before mating and continued until delivery. After birth, the pups were not exposed to CS until day 21 (D21). Between D21 and D49, corresponding to “adolescence,” litters were randomized for an additional 4 weeks of exposure to CS. Lung morphometry, lung mechanics, and the expression of genes involved in senescence were evaluated in different subsets of mice on D21 and D49. Results: In utero exposure to CS induced significant lung function impairment by D21. CS exposure between D21 and D49 induced significant functional impairment only in mice exposed to CS prenatally. On D49, no difference was observed between subgroups in terms of lung p53, p16, p21, and Bax mRNA levels. Conclusions: Our findings suggest that prenatal and adolescent CS exposure have a synergistic effect on lung function in mice. The combined effect did not appear to be a consequence of early pulmonary senescence. Citation: Drummond D, Baravalle-Einaudi M, Lezmi G, Vibhushan S, Franco-Montoya ML, Hadchouel A, Boczkowski J, Delacourt C. 2017. Combined effects of in utero and adolescent tobacco smoke exposure on lung function in C57Bl/6J mice. Environ Health Perspect 125:392–399; http://dx.doi.org/10.1289/EHP54 PMID:27814244

  1. Lung Volume Reduction following Recurrent Pneumonia: An Unusual Finding in a COPD Patient

    PubMed Central

    Diaz, Philip T.

    2017-01-01

    Chronic Obstructive Pulmonary Disease (COPD) is a progressive disease. Frequent pneumonias and exacerbations are known to accelerate its progression. We present a case of severe emphysema whose lung function paradoxically improved following recurrent pneumonia, without lung volume reduction surgery (LVRS). A 54-year-old female with severe COPD presented for LVRS evaluation. She was not a candidate for the surgery because of the unsuitable anatomic distribution of her emphysema. The patient experienced recurrent pneumonia over the years but her lung function and oxygen requirement showed marked improvement. Follow-up imaging studies showed decreased lung volumes and focal fibrotic changes. We believe that the improvement in her lung function overtime is the reflection of lung volume reduction as a result of parenchymal remodeling due to repeated lung infection. These findings seen in our patient contribute important information for the continued effort in developing nonsurgical lung volume reduction techniques. PMID:28373884

  2. Attenuated hypothalamic-pituitary-adrenal axis functioning predicts accelerated pubertal development in girls 1 year later.

    PubMed

    Saxbe, Darby E; Negriff, Sonya; Susman, Elizabeth J; Trickett, Penelope K

    2015-08-01

    Accelerated pubertal development has been linked to adverse early environments and may heighten subsequent mental and physical health risks. Hypothalamic-pituitary-adrenal axis functioning has been posited as a mechanism whereby stress may affect pubertal development, but the literature lacks prospective tests of this mechanism. The current study assessed 277 youth (M = 10.84 years, SD = 1.14), 138 boys and 139 girls, who reported on their pubertal development and underwent the Trier Social Stress Test for Children at baseline and returned to the laboratory approximately 1 year later (M = 1.12 years, range = 0.59-1.98 years). For girls, lower cortisol area under the curve (with respect to ground) at Time 1 predicted more advanced pubertal development at Time 2, controlling for Time 1 pubertal development. This association persisted after additional covariates including age, body mass index, race, and maltreatment history were introduced, and was driven by adrenal rather than gonadal development. Cortisol was not linked to boys' subsequent pubertal development, and no interaction by gender or by maltreatment appeared. These results suggest that attenuated cortisol, reported in other studies of children exposed to early adversity, may contribute to accelerated pubertal tempo in girls.

  3. Commissioning of helium injector for coupled radio frequency quadrupole and separated function radio frequency quadrupole accelerator.

    PubMed

    Peng, Shixiang; Chen, Jia; Ren, Haitao; Zhao, Jie; Xu, Yuan; Zhang, Tao; Zhang, Ailing; Xia, Wenlong; Gao, Shuli; Wang, Zhi; Luo, Yuting; Guo, Zhiyu; Chen, Jia'er

    2014-02-01

    A project to study a new type of acceleration structure has been launched at Peking University, in which a traditional radio frequency quadrupole (RFQ) and a separated function radio frequency quadrupole are coupled in one cavity to accelerate the He+ beam. A helium injector for this project is developed. The injector consists of a 2.45 GHz permanent magnet electron cyclotron resonance ion source and a 1.16 m long low energy beam transport (LEBT). The commissioning of this injector was carried out and an onsite test was held in June 2013. A 14 mA He+ beam with the energy of 30 keV has been delivered to the end of the LEBT, where a diaphragm with the diameter of 7 mm is located. The position of the diaphragm corresponds to the entrance of the RFQ electrodes. The beam emittance and fraction were measured after the 7 mm diaphragm. Its rms emittance is about 0.14 π mm mrad and the fraction of He+ is about 99%.

  4. Commissioning of helium injector for coupled radio frequency quadrupole and separated function radio frequency quadrupole accelerator

    SciTech Connect

    Peng, Shixiang Chen, Jia; Ren, Haitao; Zhao, Jie; Xu, Yuan; Zhang, Tao; Xia, Wenlong; Gao, Shuli; Wang, Zhi; Luo, Yuting; Guo, Zhiyu; Zhang, Ailing; Chen, Jia'er

    2014-02-15

    A project to study a new type of acceleration structure has been launched at Peking University, in which a traditional radio frequency quadrupole (RFQ) and a separated function radio frequency quadrupole are coupled in one cavity to accelerate the He+ beam. A helium injector for this project is developed. The injector consists of a 2.45 GHz permanent magnet electron cyclotron resonance ion source and a 1.16 m long low energy beam transport (LEBT). The commissioning of this injector was carried out and an onsite test was held in June 2013. A 14 mA He+ beam with the energy of 30 keV has been delivered to the end of the LEBT, where a diaphragm with the diameter of 7 mm is located. The position of the diaphragm corresponds to the entrance of the RFQ electrodes. The beam emittance and fraction were measured after the 7 mm diaphragm. Its rms emittance is about 0.14 π mm mrad and the fraction of He+ is about 99%.

  5. Basis function repetitive and feedback control with application to a particle accelerator

    NASA Astrophysics Data System (ADS)

    Akogyeram, Raphael Akuete

    2002-09-01

    The thesis addresses three problem areas within repetitive control. Firstly, it addresses issues concerning the ability of repetitive control and feedback control systems to eliminate periodic disturbances occurring above the Nyquist frequency of the hardware. Methods are developed for decomposing and unfolding notch filter or comb filter feedback control so that disturbances above Nyquist frequency can be canceled. Phenomena affecting final error levels are discussed, including error in unfolding, coarseness of zero-order hold cancellation, and waterbed effects in the feedback control system frequency response for different sample rates. Secondly, matched basis function repetitive control laws are developed for batch mode and real time implementation to converge to zero tracking error in the presence of periodic disturbances. For both control methods, conditions are given that guarantee asymptotic and monotonic convergence. Stability tests are formulated to examine stability when the period of a disturbance is not an integer number of sample times, and when there are multiple unrelated periods whose common period is too long to use. Thirdly, an understanding is developed of the optimum division of labor between the objectives accomplished by feedback and the objectives accomplished by repetitive control action. Some experimental results of the particle accelerator testbed at Thomas Jefferson National Accelerator Facility, Newport News, Virginia, are reported.

  6. A Phase I Study of Chemoradiotherapy With Use of Involved-Field Conformal Radiotherapy and Accelerated Hyperfractionation for Stage III Non-Small Cell Lung Cancer: WJTOG 3305

    SciTech Connect

    Tada, Takuhito; Chiba, Yasutaka; Tsujino, Kayoko; Fukuda, Haruyuki; Nishimura, Yasumasa; Kokubo, Masaki; Negoro, Shunichi; Kudoh, Shinzoh; Fukuoka, Masahiro; Nakagawa, Kazuhiko; Nakanishi, Yoichi

    2012-05-01

    Purpose: A Phase I study to determine a recommended dose of thoracic radiotherapy using accelerated hyperfractionation for unresectable non-small-cell lung cancer was conducted. Methods and Materials: Patients with unresectable Stage III non-small-cell lung cancer were treated intravenously with carboplatin (area under the concentration curve 2) and paclitaxel (40 mg/m{sup 2}) on Days 1, 8, 15, and 22 with concurrent twice-daily thoracic radiotherapy (1.5 Gy per fraction) beginning on Day 1 followed by two cycles of consolidation chemotherapy using carboplatin (area under the concentration curve 5) and paclitaxel (200 mg/m{sup 2}). Total doses were 54 Gy in 36 fractions, 60 Gy in 40 fractions, 66 Gy in 44 fractions, and 72 Gy in 48 fractions at Levels 1 to 4. The dose-limiting toxicity, defined as Grade {>=}4 esophagitis and neutropenic fever and Grade {>=}3 other nonhematologic toxicities, was monitored for 90 days. Results: Of 26 patients enrolled, 22 patients were assessable for response and toxicity. When 4 patients entered Level 4, enrollment was closed to avoid severe late toxicities. Dose-limiting toxicities occurred in 3 patients. They were Grade 3 neuropathy at Level 1 and Level 3 and Grade 3 infection at Level 1. However, the maximum tolerated dose was not reached. The median survival time was 28.6 months for all patients. Conclusions: The maximum tolerated dose was not reached, although the dose of radiation was escalated to 72 Gy in 48 fractions. However, a dose of 66 Gy in 44 fractions was adopted for this study because late toxicity data were insufficient.

  7. A systematic review of early life factors which adversely affect subsequent lung function.

    PubMed

    Kouzouna, A; Gilchrist, F J; Ball, V; Kyriacou, T; Henderson, J; Pandyan, A D; Lenney, W

    2016-09-01

    It has been known for many years that multiple early life factors can adversely affect lung function and future respiratory health. This is the first systematic review to attempt to analyse all these factors simultaneously. We adhered to strict a priori criteria for inclusion and exclusion of studies. The initial search yielded 29,351 citations of which 208 articles were reviewed in full and 25 were included in the review. This included 6 birth cohorts and 19 longitudinal population studies. The 25 studies reported the effect of 74 childhood factors (on their own or in combinations with other factors) on subsequent lung function reported as percent predicted forced expiration in one second (FEV1). The childhood factors that were associated with a significant reduction in future FEV1 could be grouped as: early infection, bronchial hyper-reactivity (BHR) / airway lability, a diagnosis of asthma, wheeze, family history of atopy or asthma, respiratory symptoms and prematurity / low birth weight. A complete mathematical model will only be possible if the raw data from all previous studies is made available. This highlights the need for increased cooperation between researchers and the need for international consensus about the outcome measures for future longitudinal studies.

  8. Cumulative exposure to dust and gases as determinants of lung function decline in tunnel construction workers

    PubMed Central

    Bakke, B; Ulvestad, B; Stewart, P; Eduard, W

    2004-01-01

    Aims: To study the relation between lung function decrease and cumulative exposure to dust and gases in tunnel construction workers. Methods: A total of 651 male construction workers (drill and blast workers, tunnel concrete workers, shotcreting operators, and tunnel boring machine workers) were followed up by spirometric measurements in 1989–2002 for an average of six years. Outdoor concrete workers, foremen, and engineers served as a low exposed referent population. Results: The between worker component of variability was considerably reduced within the job groups compared to the whole population, suggesting that the workers within job groups had similar exposure levels. The annual decrease in FEV1 in low-exposed non-smoking workers was 21 ml and 24 ml in low-exposed ever smokers. The annual decrease in FEV1 in tunnel construction workers was 20–31 ml higher than the low exposed workers depending on job group for both non-smokers and ever smokers. After adjustment for age and observation time, cumulative exposure to nitrogen dioxide showed the strongest association with a decrease in FEV1 in both non-smokers, and ever smokers. Conclusion: Cumulative exposure to nitrogen dioxide appeared to be a major risk factor for lung function decreases in these tunnel construction workers, although other agents may have contributed to the observed effect. Contact with blasting fumes should be avoided, diesel exhaust emissions should be reduced, and respiratory devices should be used to protect workers against dust and nitrogen dioxide exposure. PMID:14985522

  9. Exposure to grass pollen--but not birch pollen--affects lung function in Swedish children.

    PubMed

    Gruzieva, O; Pershagen, G; Wickman, M; Melén, E; Hallberg, J; Bellander, T; Lõhmus, M

    2015-09-01

    Allergic response to pollen is increasing worldwide, leading to high medical and social costs. However, the effect of pollen exposure on lung function has rarely been investigated. Over 1800 children in the Swedish birth cohort BAMSE were lung-function- and IgE-tested at the age of 8 and 16 years old. Daily concentrations for 9 pollen types together with measurements for ozone, NO2 , PM10 , PM2.5 were estimated for the index day as well as up to 6 days before the testing. Exposure to grass pollen during the preceding day was associated with a reduced forced expiratory volume in 8-yr-olds; -32.4 ml; 95% CI: -50.6 to -14.2, for an increase in three pollen counts/m³. Associations appeared stronger in children sensitized to pollen allergens. As the grass species flower late in the pollen season, the allergy care routines might be weakened during this period. Therefore, allergy information may need to be updated to increase awareness among grass pollen-sensitized individuals.

  10. Multi-functionalized carbon dots as theranostic nanoagent for gene delivery in lung cancer therapy.

    PubMed

    Wu, Yu-Fen; Wu, Hsi-Chin; Kuan, Chen-Hsiang; Lin, Chun-Jui; Wang, Li-Wen; Chang, Chien-Wen; Wang, Tzu-Wei

    2016-02-16

    Theranostics, an integrated therapeutic and diagnostic system, can simultaneously monitor the real-time response of therapy. Different imaging modalities can combine with a variety of therapeutic moieties in theranostic nanoagents. In this study, a multi-functionalized, integrated theranostic nanoagent based on folate-conjugated reducible polyethylenimine passivated carbon dots (fc-rPEI-Cdots) is developed and characterized. These nanoagents emit visible blue photoluminescence under 360 nm excitation and can encapsulate multiple siRNAs (EGFR and cyclin B1) followed by releasing them in intracellular reductive environment. In vitro cell culture study demonstrates that fc-rPEI-Cdots is a highly biocompatible material and a good siRNA gene delivery carrier for targeted lung cancer treatment. Moreover, fc-rPEI-Cdots/pooled siRNAs can be selectively accumulated in lung cancer cells through receptor mediated endocytosis, resulting in better gene silencing and anti-cancer effect. Combining bioimaging of carbon dots, stimulus responsive property, gene silencing strategy, and active targeting motif, this multi-functionalized, integrated theranostic nanoagent may provide a useful tool and platform to benefit clinicians adjusting therapeutic strategy and administered drug dosage in real time response by monitoring the effect and tracking the development of carcinomatous tissues in diagnostic and therapeutic aspects.

  11. Lung function, transfusion, pulmonary capillary blood volume and sickle cell disease.

    PubMed

    Lunt, Alan; McGhee, Emily; Robinson, Polly; Rees, David; Height, Susan; Greenough, Anne

    2016-02-01

    Lung function abnormalities occur in children with sickle cell disease (SCD) and may be associated with elevated pulmonary blood volume. To investigate that association, we determined whether blood transfusion in SCD children acutely increased pulmonary capillary blood volume (PCBV) and increased respiratory system resistance (Rrs5). Measurements of Rrs5 and spirometry were made before and after blood transfusion in 18 children, median age 14.2 (6.6-18.5) years. Diffusing capacity for carbon monoxide and nitric oxide were assessed to calculate the PCBV. Post transfusion, the median Rrs5 had increased from 127.4 to 141.3% predicted (p<0.0001) and pulmonary capillary blood volume from 39.7 to 64.1 ml/m2 (p<0.0001); forced expiratory volume in one second (p=0.0056) and vital capacity (p=0.0008) decreased. The increase in Rrs5 correlated with the increase in PCBV (r=0.50, p=0.0493). Increased pulmonary capillary blood volume may at least partially explain the lung function abnormalities in SCD children.

  12. Toxocariasis and lung function: relevance of a neglected infection in an urban landscape.

    PubMed

    Walsh, Michael G; Haseeb, M A

    2014-03-01

    Toxocariasis has been highlighted as a potentially important neglected infection of poverty in developed countries that experience substantive health disparities such as the United States. An association between Toxocara infection and lung function, in concert with a relatively high prevalence of infection, may mark an important mechanism by which this infection could contribute significantly to the differential morbidity across different socioeconomic groups and landscapes. To assess the potential relevance of this infection in a dense urban environment, we measured the association between forced expiratory volume in 1 second (FEV₁) and serology diagnosed Toxocara infection in a sample of US-born New York City residents. We identified a significant independent association between Toxocara infection and lung function, wherein those with previous Toxocara infection had a 236.9 mL reduced FEV₁ compared to those without Toxocara infection even after adjusting for age, sex, ethnicity, level of education, smoking status, body mass index, and pet ownership. These findings from New York City corroborate similar findings in a national sample and, while the cross-sectional data preclude a direct causal relationship, this study identifies a potentially important neglected infection in a dense urban landscape.

  13. Multi-functionalized carbon dots as theranostic nanoagent for gene delivery in lung cancer therapy

    PubMed Central

    Wu, Yu-Fen; Wu, Hsi-Chin; Kuan, Chen-Hsiang; Lin, Chun-Jui; Wang, Li-Wen; Chang, Chien-Wen; Wang, Tzu-Wei

    2016-01-01

    Theranostics, an integrated therapeutic and diagnostic system, can simultaneously monitor the real-time response of therapy. Different imaging modalities can combine with a variety of therapeutic moieties in theranostic nanoagents. In this study, a multi-functionalized, integrated theranostic nanoagent based on folate-conjugated reducible polyethylenimine passivated carbon dots (fc-rPEI-Cdots) is developed and characterized. These nanoagents emit visible blue photoluminescence under 360 nm excitation and can encapsulate multiple siRNAs (EGFR and cyclin B1) followed by releasing them in intracellular reductive environment. In vitro cell culture study demonstrates that fc-rPEI-Cdots is a highly biocompatible material and a good siRNA gene delivery carrier for targeted lung cancer treatment. Moreover, fc-rPEI-Cdots/pooled siRNAs can be selectively accumulated in lung cancer cells through receptor mediated endocytosis, resulting in better gene silencing and anti-cancer effect. Combining bioimaging of carbon dots, stimulus responsive property, gene silencing strategy, and active targeting motif, this multi-functionalized, integrated theranostic nanoagent may provide a useful tool and platform to benefit clinicians adjusting therapeutic strategy and administered drug dosage in real time response by monitoring the effect and tracking the development of carcinomatous tissues in diagnostic and therapeutic aspects. PMID:26880047

  14. Endotoxin and gender modify lung function recovery after occupational organic dust exposure: a 30 year study

    PubMed Central

    Valeri, Linda; Zhang, Feng-ying; Zheng, Bu-Yong; Mehta, Amar J.; Shi, Jing; Su, Li; Brown, Dan; Eisen, Ellen A; Christiani, David C.

    2015-01-01

    OBJECTIVES The purpose of this study is to determine the trajectory of lung function change after exposure cessation to occupational organic dust exposure, and to identify factors that modify improvement. METHODS The Shanghai Textile Worker Study is a longitudinal study of 447 cotton workers exposed to endotoxin-containing dust and 472 silk workers exposed to non-endotoxin-containing dust. Spirometry was performed at 5 year intervals. Air sampling was performed to estimate individual cumulative exposures. The effect of work cessation on FEV1 was modeled using generalized additive mixed effects models to identify the trajectory of FEV1 recovery. Linear mixed effects models incorporating interaction terms were used to identify modifiers of FEV1 recovery. Loss to follow-up was accounted for with inverse probability of censoring weights. RESULTS 74.2% of the original cohort still alive participated in 2011. Generalized additive mixed models identified a non-linear improvement in FEV1 for all workers after exposure cessation, with no plateau noted 25 years after retirement. Linear mixed effects models incorporating interaction terms identified prior endotoxin exposure (p=0.01) and male gender (p=0.002) as risk factors for impaired FEV1 improvement after exposure cessation. After adjusting for gender, smoking delayed the onset of FEV1 gain but did not affect the overall magnitude of change. CONCLUSIONS Lung function improvement after cessation of exposure to organic dust is sustained. Endotoxin exposure and male gender are risk factors for less FEV1 improvement. PMID:25666844

  15. Age and height dependence of lung clearance index and functional residual capacity.

    PubMed

    Lum, Sooky; Stocks, Janet; Stanojevic, Sanja; Wade, Angie; Robinson, Paul; Gustafsson, Per; Brown, Meghan; Aurora, Paul; Subbarao, Padmaja; Hoo, Ah-Fong; Sonnappa, Samatha

    2013-06-01

    The lung clearance index (LCI) is more sensitive than spirometry in detecting abnormal lung function in children with cystic fibrosis. LCI is thought to be independent of age, but recent evidence suggests that the upper limit of normal is higher in infants and preschool children than in older subjects. This study examines whether LCI remains independent of body size throughout childhood. Multiple-breath washout data from healthy children and adolescents were collated from three centres using the mass spectrometer system and the inert gas sulfur hexafluoride. Reference equations for LCI and functional residual capacity (FRC) were constructed using the LMS (lambda-mu-sigma) method. Data were available from 497 subjects (2 weeks to 19 years of age) tested on 659 occasions. LCI was dependent on body size, decreasing in a nonlinear pattern as height increased. Changes were particularly marked in the first 5 years of life. Height, age and sex were all independent predictors of FRC. Minimal between-centre differences allowed unified reference equations to be developed. LCI is not independent of body size. Although a constant upper normal limit would suffice for cross-sectional clinical assessments from 6 years of age, appropriate reference equations are essential for accurate interpretation of results during early childhood.

  16. Functional polyesters enable selective siRNA delivery to lung cancer over matched normal cells

    PubMed Central

    Yan, Yunfeng; Liu, Li; Xiong, Hu; Miller, Jason B.; Zhou, Kejin; Kos, Petra; Huffman, Kenneth E.; Elkassih, Sussana; Norman, John W.; Carstens, Ryan; Kim, James; Minna, John D.; Siegwart, Daniel J.

    2016-01-01

    Conventional chemotherapeutics nonselectively kill all rapidly dividing cells, which produces numerous side effects. To address this challenge, we report the discovery of functional polyesters that are capable of delivering siRNA drugs selectively to lung cancer cells and not to normal lung cells. Selective polyplex nanoparticles (NPs) were identified by high-throughput library screening on a unique pair of matched cancer/normal cell lines obtained from a single patient. Selective NPs promoted rapid endocytosis into HCC4017 cancer cells, but were arrested at the membrane of HBEC30-KT normal cells during the initial transfection period. When injected into tumor xenografts in mice, cancer-selective NPs were retained in tumors for over 1 wk, whereas nonselective NPs were cleared within hours. This translated to improved siRNA-mediated cancer cell apoptosis and significant suppression of tumor growth. Selective NPs were also able to mediate gene silencing in xenograft and orthotopic tumors via i.v. injection or aerosol inhalation, respectively. Importantly, this work highlights that different cells respond differentially to the same drug carrier, an important factor that should be considered in the design and evaluation of all NP carriers. Because no targeting ligands are required, these functional polyester NPs provide an exciting alternative approach for selective drug delivery to tumor cells that may improve efficacy and reduce adverse side effects of cancer therapies. PMID:27621434

  17. Longitudinal Lung Function Growth of Mexican Children Compared with International Studies

    PubMed Central

    Martínez-Briseño, David; Fernández-Plata, Rosario; Gochicoa-Rangel, Laura; Torre-Bouscoulet, Luis; Rojas-Martínez, Rosalba; Mendoza, Laura; García-Sancho, Cecilia; Pérez-Padilla, Rogelio

    2013-01-01

    Introduction Our aim was to compare the longitudinal lung function growth of Mexican children and adolescents with the collated spirometric reference proposed for international use and with that of Mexican-Americans from the National Health State Examination Survey III (NHANES) III study. Materials and Methods A cohort of Mexican children in third year of primary school was followed with spirometry twice a year through secondary school. Multilevel mixed-effects lineal models separated by gender were fit for the spirometric variables of 2,641 respiratory-healthy Mexican children expressed as Z-scores of tested reference equations. Impact of adjustment by sitting height on differences with Mexican-American children was observed in a subsample of 1,987 children. Results At same gender, age, and height, Mexican children had increasingly higher forced expiratory volume in 1 s (FEV1) and Forced vital capacity (FVC) than the children from the collated reference study (mean Z-score, 0.68 for FEV1 and 0.51 for FVC) and than Mexican-American children (Z-score, 0.23 for FEV1 and 0.21 for FVC) respectively. Differences with Mexican-Americans were not reduced by adjusting by sitting height. Conclusions For reasons that remain unclear, the gender-, age-, and height-adjusted lung function of children from Mexico City is higher than that reported by several international studies. PMID:24143231

  18. [Diffuse infiltrative lung disease in scleroderma. Analysis of radio-clinical and functional semiology].

    PubMed

    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.

  19. Lung function in children in relation to ethnicity, physique and socioeconomic factors.

    PubMed

    Lum, Sooky; Bountziouka, Vassiliki; Sonnappa, Samatha; Wade, Angie; Cole, Tim J; Harding, Seeromanie; Wells, Jonathan C K; Griffiths, Chris; Treleaven, Philip; Bonner, Rachel; Kirkby, Jane; Lee, Simon; Raywood, Emma; Legg, Sarah; Sears, Dave; Cottam, Philippa; Feyeraband, Colin; Stocks, Janet

    2015-12-01

    Can ethnic differences in spirometry be attributed to differences in physique and socioeconomic factors?Assessments were undertaken in 2171 London primary schoolchildren on two occasions 1 year apart, whenever possible, as part of the Size and Lung function In Children (SLIC) study. Measurements included spirometry, detailed anthropometry, three-dimensional photonic scanning for regional body shape, body composition, information on ethnic ancestry, birth and respiratory history, socioeconomic circumstances, and tobacco smoke exposure.Technically acceptable spirometry was obtained from 1901 children (mean (range) age 8.3 (5.2-11.8) years, 46% boys, 35% White, 29% Black-African origin, 24% South-Asian, 12% Other/mixed) on 2767 test occasions. After adjusting for sex, age and height, forced expiratory volume in 1 s was 1.32, 0.89 and 0.51 z-score units lower in Black-African origin, South-Asian and Other/mixed ethnicity children, respectively, when compared with White children, with similar decrements for forced vital capacity (p<0.001 for all). Although further adjustment for sitting height and chest width reduced differences attributable to ethnicity by up to 16%, significant differences persisted after adjusting for all potential determinants, including socioeconomic circumstances.Ethnic differences in spirometric lung function persist despite adjusting for a wide range of potential determinants, including body physique and socioeconomic circumstances, emphasising the need to use ethnic-specific equations when interpreting results.

  20. Occupation, chronic bronchitis, and lung function in young adults. An international study.

    PubMed

    Zock, J P; Sunyer, J; Kogevinas, M; Kromhout, H; Burney, P; Antó, J M

    2001-06-01

    We studied the relationship between occupational exposures, chronic bronchitis, and lung function in a general population survey in 14 industrialized countries, including 13,253 men and women aged 20 to 44 yr. We studied associations between occupational group, occupational exposures, bronchitis symptoms (cough and phlegm production for at least 3 mo each year), FEV(1), and nonspecific bronchial responsiveness (NSBR) separately in lifetime nonsmokers, cigarette smokers, and ex-smokers. Occupational exposure to vapors, gas, dust, or fumes, estimated with a job exposure matrix (JEM), was associated with chronic bronchitis among current smokers only (prevalence ratio (PR): 1.2 to 1.7). The interaction of occupational exposure with smoking, however, was not statistically significant (p > 0.1). Self-reported exposure was related to chronic bronchitis in all smoking groups. An increased risk for chronic bronchitis was found in agricultural, textile, paper, wood, chemical, and food processing workers, being more pronounced in smokers. Lung function and NSBR were not clearly related to occupational exposures. Findings were similar for asthmatic and nonasthmatic subjects. In conclusion, occupational exposures contributed to the occurrence of chronic (industrial) bronchitis in young adults. Fixed airflow limitation was not evident, probably due to the relatively young age of this population.

  1. Effect of artificial gravity with exercise training on lung function during head-down bed rest in humans.

    PubMed

    Guo, Yinghua; Guo, Na; Liu, Changting; Wang, Delong; Wang, Junfeng; Sun, Xiqing; Fan, Shangchun; Wang, Changyong; Yang, Changbin; Zhang, Yu; Lu, Dongyuan; Yao, Yongjie

    2013-01-01

    There is evidence to suggest that microgravity/weightlessness can induce changes in lung physiology/function. We hypothesized that microgravity, induced by head-down bed rest (HDBR), would induce changes in lung function and that exercise training with artificial gravity (AG) would prevent these changes from occurring. Twelve participants were randomly assigned to a control or AG exercise countermeasure (CM) group (n = 6 per group) and 96 h of 6° HDBR. Participants in the CM group were exposed to AG (alternating 2 min intervals of +1·0 and +2·0 G) for 30 min, twice daily, during which time ergometric exercise (40 W intensity) was performed. Pulse rate, oxygen saturation (SO(2) ) and lung function were measured and compared between groups. The CM and control groups were similar in mean age, height and weight. There were no significant within or between group differences over time in pulse rate, SO(2) , vital capacity, inspiratory capacity, tidal volume, expiratory reserve volume, inspiratory reserve volume, minute ventilation, forced vital capacity, forced expiratory volume in 1 s, peak expiratory flow, maximal expiratory flow in 25%, 50% and 75% vital capacity, forced inspiratory vital capacity, forced inspiratory volume in 1 s and maximal voluntary ventilation. Microgravity induced by 96 h of HDBR does not appear to affect lung function in humans. Further, AG with exercise training does not change lung function during 96 h of HDBR in humans.

  2. Measurement of lung function using Electrical Impedance Tomography (EIT) during mechanical ventilation

    NASA Astrophysics Data System (ADS)

    Nebuya, Satoru; Koike, Tomotaka; Imai, Hiroshi; Noshiro, Makoto; Brown, Brian H.; Soma, Kazui

    2010-04-01

    The consistency of regional lung density measurements as estimated by Electrical Impedance Tomography (EIT), in eleven patients supported by a mechanical ventilator, was validated to verify the feasibility of its use in intensive care medicine. There were significant differences in regional lung densities between the normal lung and diseased lungs associated with pneumonia, atelectasis and pleural effusion (Steel-Dwass test, p < 0.05). Temporal changes in regional lung density of patients with atelectasis were observed to be in good agreement with the results of clinical diagnosis. These results indicate that it is feasible to obtain a quantitative value for regional lung density using EIT.

  3. Whittaker functions in beam driven plasma wakefield acceleration for a plasma with a parabolic density profile

    SciTech Connect

    Golian, Y.; Dorranian, D.; Aslaninejad, M.

    2016-01-15

    A model for the interaction of charged particle beams and plasma for a linear wakefield generation in a parabolic plasma channel is presented. The density profile has the maximum on the axis. A Gaussian proton beam is employed to excite the plasma wakefield in the channel. We have built a thorough analytical model and solved the governing equations for the wakefield acceleration of a charged particle beam. The longitudinal and radial wakefields are expressed by Whittaker functions, and for certain parameters of plasma and the beam, their behaviours in longitudinal and radial directions are investigated. It is observed that the radial electric field generated by the bunch increases with the distance behind the bunch.

  4. Exposure to 9,10-phenanthrenequinone accelerates malignant progression of lung cancer cells through up-regulation of aldo-keto reductase 1B10

    SciTech Connect

    Matsunaga, Toshiyuki; Morikawa, Yoshifumi; Haga, Mariko; Endo, Satoshi; Soda, Midori; Yamamura, Keiko; El-Kabbani, Ossama; Tajima, Kazuo; Ikari, Akira; Hara, Akira

    2014-07-15

    Inhalation of 9,10-phenanthrenequinone (9,10-PQ), a major quinone in diesel exhaust, exerts fatal damage against a variety of cells involved in respiratory function. Here, we show that treatment with high concentrations of 9,10-PQ evokes apoptosis of lung cancer A549 cells through production of reactive oxygen species (ROS). In contrast, 9,10-PQ at its concentrations of 2 and 5 μM elevated the potentials for proliferation, invasion, metastasis and tumorigenesis, all of which were almost completely inhibited by addition of an antioxidant N-acetyl-L-cysteine, inferring a crucial role of ROS in the overgrowth and malignant progression of lung cancer cells. Comparison of mRNA expression levels of six aldo-keto reductases (AKRs) in the 9,10-PQ-treated cells advocated up-regulation of AKR1B10 as a major cause contributing to the lung cancer malignancy. In support of this, the elevation of invasive, metastatic and tumorigenic activities in the 9,10-PQ-treated cells was significantly abolished by the addition of a selective AKR1B10 inhibitor oleanolic acid. Intriguingly, zymographic and real-time PCR analyses revealed remarkable increases in secretion and expression, respectively, of matrix metalloproteinase 2 during the 9,10-PQ treatment, and suggested that the AKR1B10 up-regulation and resultant activation of mitogen-activated protein kinase cascade are predominant mechanisms underlying the metalloproteinase induction. In addition, HPLC analysis and cytochrome c reduction assay in in vitro 9,10-PQ reduction by AKR1B10 demonstrated that the enzyme catalyzes redox-cycling of this quinone, by which ROS are produced. Collectively, these results suggest that AKR1B10 is a key regulator involved in overgrowth and malignant progression of the lung cancer cells through ROS production due to 9,10-PQ redox-cycling. - Highlights: • 9,10-PQ promotes invasion, metastasis and tumorigenicity in lung cancer cells. • The 9,10-PQ-elicited promotion is possibly due to AKR1B10 up

  5. The innate immune function of airway epithelial cells in inflammatory lung disease

    PubMed Central

    Hiemstra, Pieter S.; McCray, Paul B.; Bals, Robert

    2016-01-01

    The airway epithelium is now considered central to the orchestration of pulmonary inflammatory and immune responses, and is also key to tissue remodelling. It acts as a first barrier in the defence against a wide range of inhaled challenges, and is critically involved in the regulation of both innate and adaptive immune responses to these challenges. Recent progress in our understanding of the developmental regulation of this tissue, the differentiation pathways, recognition of pathogens and antimicrobial responses is now exploited to help understand how epithelial cell function and dysfunction contributes to the pathogenesis of a variety of inflammatory lung diseases. In the review, advances in our knowledge of the biology of airway epithelium, as well as its role and (dys)function in asthma, COPD and cystic fibrosis, are discussed. PMID:25700381

  6. Respiratory symptoms, lung function, and nasal cellularity in Indonesian wood workers: a dose-response analysis

    PubMed Central

    Borm, P; Jetten, M; Hidayat, S; van de Burgh, N; Leunissen, P; Kant, I; Houba, R; Soeprapto, H

    2002-01-01

    Objectives: It was hypothesised that inflammation plays a dominant part in the respiratory effects of exposure to wood dust. The purpose of this study was to relate the nasal inflammatory responses of workers exposed to meranti wood dust to (a) levels of exposure, (b) respiratory symptoms and (c) respiratory function. Methods: A cross sectional study was carried out in 1997 in a woodworking plant that used mainly meranti, among 982 workers exposed to different concentrations of wood dust. Personal sampling (n=243) of inhalable dust measurements indicated mean exposure in specific jobs, and enabled classification of 930 workers in three exposure classes (<2, 2–5, and >5 mg/m3) based on job title. Questionnaires were used to screen respiratory symptoms in the entire population. Lung function was measured with two different techniques, conventional flow-volume curves and the forced oscillation technique. Nasal lavage was done to assess inflammation in the upper respiratory tract. Results: A negative trend between years of employment and most flow-volume variables was found in men, but not in women workers. Current exposure, however, was not related to spirometric outcomes, respiratory symptoms, or nasal cellularity. Some impedance variables were related to current exposure but also with better function at higher exposure. Conclusions: Exposure to meranti wood dust did not cause an inflammation in the upper respiratory tract nor an increase of respiratory symptoms or decrease of lung function. These data do not corroborate the hypothesis that inflammation plays a part in airway obstruction induced by wood dust. PMID:11983850

  7. Assessing the functional mechanical properties of bioengineered organs with emphasis on the lung.

    PubMed

    Suki, Béla

    2014-09-01

    Recently, an exciting new approach has emerged in regenerative medicine pushing the forefront of tissue engineering to create bioartificial organs. The basic idea is to create biological scaffolds made of extracellular matrix (ECM) that preserves the three-dimensional architecture of an entire organ. These scaffolds are then used as templates for functional tissue and organ reconstruction after re-seeding the structure with stem cells or appropriately differentiated cells. In order to make sure that these bioartificial organs will be able to function in the mechanical environment of the native tissue, it is imperative to fully characterize their mechanical properties and match them with those of the normal native organs. This mini-review briefly summarizes modern measurement techniques of mechanical function characterized mostly by the material or volumetric stiffness. Micro-scale and macro-scale techniques such as atomic force microscopy and the tissue strip stress-strain approach are discussed with emphasis on those that combine mechanical measurements with structural visualization. Proper micro-scale stiffness helps attachment and differentiation of cells in the bioartificial organ whereas macro-scale functionality is provided by the overall mechanical properties of the construct. Several approaches including failure mechanics are also described, which specifically probe the contributions of the main ECM components including collagen, elastin, and proteoglycans to organ level ECM function. Advantages, drawbacks, and possible pitfalls as well as interpretation of the data are given throughout. Finally, specific techniques to assess the functionality of the ECM of bioartificial lungs are separately discussed.

  8. Reduced Lung Function in a Chronic Asthma Model Is Associated with Prolonged Inflammation, but Independent of Peribronchial Fibrosis

    PubMed Central

    Koerner-Rettberg, Cordula; Doths, Sandra; Stroet, Anke; Schwarze, Jürgen

    2008-01-01

    Background In asthma, mechanisms contributing to chronicity remain to be determined. Recent models of sensitisation with prolonged airway allergen challenges reproduce typical features of chronic asthma. However, the interplay between inflammation, structural changes and lung function is poorly understood. This study was performed to delineate functional, structural and immunological airway changes after cessation of long term challenges to elucidate factors contributing to the development of prolonged lung function changes. Methodology/Principal Findings Mice sensitised systemically were consecutively challenged intranasally with ovalbumin for two or eight weeks. After the end of challenges, lung function, airway inflammation, features of airway remodelling, local T-cell cytokines and systemic ovalbumin-specific antibodies were monitored. Long term challenges resulted in airway hyperresponsiveness lasting 2 weeks and reduced baseline lung function for 6 weeks after their cessation. In contrast, these changes resolved within one week after short term challenges. Prolonged transforming growth factor beta (TGF-β)1 production and marked peribronchial fibrosis were only induced by long term challenges. Importantly, fibrosis became apparent only after the onset of lung function changes and outlasted them. Further, long term challenges led to prolonged and intense airway inflammation with marked lymphocytosis, but moderate eosinophilia, sustained IL-5 production and ovalbumin-specific IgG2a antibodies, the latter suggesting a Th1 component to the immune response. In contrast, following short term challenges airway inflammation was dominated by eosinophils and associated with a strong, but transient IL-13 response. Conclusions Prolonged lung function changes after long term allergen challenges seem to develop and resolve independently of the persistent peribronchial fibrosis. They are more closely associated with intense airway inflammation, marked lymphocytosis

  9. Exposures and cross-shift lung function declines in wildland firefighters.

    PubMed

    Gaughan, Denise M; Piacitelli, Chris A; Chen, Bean T; Law, Brandon F; Virji, M Abbas; Edwards, Nicole T; Enright, Paul L; Schwegler-Berry, Diane E; Leonard, Stephen S; Wagner, Gregory R; Kobzik, Lester; Kales, Stefanos N; Hughes, Michael D; Christiani, David C; Siegel, Paul D; Cox-Ganser, Jean M; Hoover, Mark D

    2014-01-01

    Respiratory problems are common among wildland firefighters. However, there are few studies directly linking occupational exposures to respiratory effects in this population. Our objective was to characterize wildland fire fighting occupational exposures and assess their associations with cross-shift changes in lung function. We studied 17 members of the Alpine Interagency Hotshot Crew with environmental sampling and pulmonary function testing during a large wildfire. We characterized particles by examining size distribution and mass concentration, and conducting elemental and morphological analyses. We examined associations between cross-shift lung function change and various analytes, including levoglucosan, an indicator of wood smoke from burning biomass. The levoglucosan component of the wildfire aerosol showed a predominantly bimodal size distribution: a coarse particle mode with a mass median aerodynamic diameter about 12 μm and a fine particle mode with a mass median aerodynamic diameter < 0.5 μm. Levoglucosan was found mainly in the respirable fraction and its concentration was higher for fire line construction operations than for mop-up operations. Larger cross-shift declines in forced expiratory volume in one second were associated with exposure to higher concentrations of respirable levoglucosan (p < 0.05). Paired analyses of real-time personal air sampling measurements indicated that higher carbon monoxide (CO) concentrations were correlated with higher particulate concentrations when examined by mean values, but not by individual data points. However, low CO concentrations did not provide reliable assurance of concomitantly low particulate concentrations. We conclude that inhalation of fine smoke particles is associated with acute lung function decline in some wildland firefighters. Based on short-term findings, it appears important to address possible long-term respiratory health issues for wildland firefighters. [Supplementary materials are

  10. ACTH4 -10, Substance P, and Dizolcipine (Mk-801) Accelerate Functional Recovery After Hemilabyrinthectomy in Goldfish

    PubMed Central

    Mattioli, R.; Huston, J. P.; Spieler, R. E.

    2000-01-01

    In this study, we evaluated the goldfish model of hemilabyrinthectomy for investigating potential recovery-promoting drugs. In this lesion model, the unilateral removal of the labyrinth induces a postural imbalance in response to light (Dorsal Light Reflex), from which the animals can recover over time. The behavioral effects of two neuropeptides were tested–namely, of substance P and ACTH4-10, both of which are known to promote functional recovery in several other lesion models. Furthermore, the effect of MK- 801, an antagonist of the glutamatergic NMDAreceptor subtype, was tested because this substance has also been shown to exert a neuroprotective effect. After lesion of the right labyrinth, the animals (n=12) were treated intraperitoneally daily either with vehicle (n=12), substance P (n=11), ACTH4-10 (n=12), or MK- 801 (n=12). Another group (n=11), which served as a non-lesion control, did not receive hemilabyrinthectomy or systemic injections. The lesion group, treated post-operatively with vehicle, did not recover from the postural deviation over the 24-d testing period. In contrast, all three test substances accelerated the functional recovery after unilateral labyrinthectomy. The decrease of the dorsal light reflex persisted even after cessation of drug treatment after 20d. The results indicate that using the dorsal light reflex in the model of hemilabyrinthectomy in goldfish provides a useful approach to studying the ability of potential new neurotrophic or neuroprotective drugs to promote functional recovery. PMID:11486488

  11. Role of reactive nitrogen species generated via inducible nitric oxide synthase in vesicant-induced lung injury, inflammation and altered lung functioning

    SciTech Connect

    Sunil, Vasanthi R.; Shen, Jianliang; Patel-Vayas, Kinal; Gow, Andrew J.; Laskin, Jeffrey D.; Laskin, Debra L.

    2012-05-15

    altered lung functioning.

  12. The effects of second-hand and direct exposure to tobacco smoke on asthma and lung function in adolescence.

    PubMed

    Tager, Ira B

    2008-03-01

    Cigarette smoking still is quite common in many parts of the world. In parallel, exposure to second-hand smoke continues to be common despite declines in smoking in developed countries and despite evidence of serious health effects in infants and children. This paper focuses on the effects of second-hand and direct exposure (personal smoking) on the respiratory health of adolescents, in particular effects on the occurrence of asthma and on lung function. Published data indicate that, in addition to whatever effects direct and postnatal second-hand tobacco smoke exposure have on the occurrence of asthma and impaired levels and growth of lung function in adolescents, there is an underlying alteration in the prenatal and early postnatal development of the structural and mechanical characteristics of the lung that contribute substantially to these deficits. These developmental effects may be important contributors to the future risks for impaired pulmonary function.

  13. The Ser82 RAGE Variant Affects Lung Function and Serum RAGE in Smokers and sRAGE Production In Vitro

    PubMed Central

    Miller, Suzanne; Henry, Amanda P.; Hodge, Emily; Kheirallah, Alexander K.; Billington, Charlotte K.; Rimington, Tracy L.; Bhaker, Sangita K.; Obeidat, Ma’en; Melén, Erik; Merid, Simon K.; Swan, Caroline; Gowland, Catherine; Nelson, Carl P.; Stewart, Ceri E.; Bolton, Charlotte E.; Kilty, Iain; Malarstig, Anders; Parker, Stuart G.; Moffatt, Miriam F.; Wardlaw, Andrew J.; Hall, Ian P.; Sayers, Ian

    2016-01-01

    Introduction Genome-Wide Association Studies have identified associations between lung function measures and Chronic Obstructive Pulmonary Disease (COPD) and chromosome region 6p21 containing the gene for the Advanced Glycation End Product Receptor (AGER, encoding RAGE). We aimed to (i) characterise RAGE expression in the lung, (ii) identify AGER transcripts, (iii) ascertain if SNP rs2070600 (Gly82Ser C/T) is associated with lung function and serum sRAGE levels and (iv) identify whether the Gly82Ser variant is functionally important in altering sRAGE levels in an airway epithelial cell model. Methods Immunohistochemistry was used to identify RAGE protein expression in 26 human tissues and qPCR was used to quantify AGER mRNA in lung cells. Gene expression array data was used to identify AGER expression during lung development in 38 fetal lung samples. RNA-Seq was used to identify AGER transcripts in lung cells. sRAGE levels were assessed in cells and patient serum by ELISA. BEAS2B-R1 cells were transfected to overexpress RAGE protein with either the Gly82 or Ser82 variant and sRAGE levels identified. Results Immunohistochemical assessment of 6 adult lung samples identified high RAGE expression in the alveoli of healthy adults and individuals with COPD. AGER/RAGE expression increased across developmental stages in human fetal lung at both the mRNA (38 samples) and protein levels (20 samples). Extensive AGER splicing was identified. The rs2070600T (Ser82) allele is associated with higher FEV1, FEV1/FVC and lower serum sRAGE levels in UK smokers. Using an airway epithelium model overexpressing the Gly82 or Ser82 variants we found that HMGB1 activation of the RAGE-Ser82 receptor results in lower sRAGE production. Conclusions This study provides new information regarding the expression profile and potential role of RAGE in the human lung and shows a functional role of the Gly82Ser variant. These findings advance our understanding of the potential mechanisms underlying

  14. Tumor Suppressor Function of the SEMA3B Gene in Human Lung and Renal Cancers

    PubMed Central

    Senchenko, Vera N.; Pronina, Irina V.; Khodyrev, Dmitry S.; Kudryavtseva, Anna V.; Krasnov, George S.; Gerashchenko, Ganna V.; Chashchina, Larisa I.; Kazubskaya, Tatiana P.; Kondratieva, Tatiana T.; Lerman, Michael I.; Angeloni, Debora; Braga, Eleonora A.; Kashuba, Vladimir I.

    2015-01-01

    The SEMA3B gene is located in the 3p21.3 LUCA region, which is frequently affected in different types of cancer. The objective of our study was to expand our knowledge of the SEMA3B gene as a tumor suppressor and the mechanisms of its inactivation. In this study, several experimental approaches were used: tumor growth analyses and apoptosis assays in vitro and in SCID mice, expression and methylation assays and other. With the use of the small cell lung cancer cell line U2020 we confirmed the function of SEMA3B as a tumor suppressor, and showed that the suppression can be realized through the induction of apoptosis and, possibly, associated with the inhibition of angiogenesis. In addition, for the first time, high methylation frequencies have been observed in both intronic (32-39%) and promoter (44-52%) CpG-islands in 38 non-small cell lung carcinomas, including 16 squamous cell carcinomas (SCC) and 22 adenocarcinomas (ADC), and in 83 clear cell renal cell carcinomas (ccRCC). Correlations between the methylation frequencies of the promoter and the intronic CpG-islands of SEMA3B with tumor stage and grade have been revealed for SCC, ADC and ccRCC. The association between the decrease of the SEMA3B mRNA level and hypermethylation of the promoter and the intronic CpG-islands has been estimated in renal primary tumors (P < 0.01). Using qPCR, we observed on the average 10- and 14-fold decrease of the SEMA3B mRNA level in SCC and ADC, respectively, and a 4-fold decrease in ccRCC. The frequency of this effect was high in both lung (92-95%) and renal (84%) tumor samples. Moreover, we showed a clear difference (P < 0.05) of the SEMA3B relative mRNA levels in ADC with and without lymph node metastases. We conclude that aberrant expression and methylation of SEMA3B could be suggested as markers of lung and renal cancer progression. PMID:25961819

  15. Lung function and six-minute walk test performance in individuals with sickle cell disease

    PubMed Central

    Ohara, Daniela G.; Ruas, Gualberto; Walsh, Isabel A. P.; Castro, Shamyr S.; Jamami, Mauricio

    2014-01-01

    Background Sickle Cell Disease (SCD), which is characterized by a mutation in the gene encoding beta hemoglobin, causes bodily dysfunctions such as impaired pulmonary function and reduced functional capacity. Objective To assess changes in pulmonary function and functional capacity in patients with SCD and to identify the relationships between these variables. Method We evaluated sociodemographic, anthropometric, lung function (spirometry), respiratory (manovacuometer), peripheral muscle strength (Handgrip strength - HS) and functional capacity (i.e., the six-minute walk test) parameters in 21 individuals with SCD (average age of 29±6 years). Shapiro-Wilk, paired Student's, Wilcoxon, Pearson and Spearman correlation tests were used for statistical analyses, and the significance threshold was set at p<0.05. Results A total of 47.6% of the study subjects exhibited an altered ventilation pattern, 42.8% had a restrictive ventilatory pattern (RVP) and 4.8% exhibited a mixed ventilatory pattern (MVP). The observed maximal inspiratory pressure (MIP) values were below the predicted values for women (64 cmH2O), and the maximum expiratory pressure (MEP) values, HS values and distance walked during the 6MWT were below the predicted values for both men (103 cmH2O, 39 Kgf and 447 m, respectively) and women (64 cmH2O; 27 Kgf; 405 m, respectively). Positive correlations were observed between maximum voluntary ventilation (MVV) and MEP (r=0.4; p=0.046); MVV and BMI (r=0.6; p=0.003); and between HS and MIP (r=0.7; p=0.001), MEP (r=0.6; p=0.002), MVV (r=0.5; p=0.015), distance walked in the 6MWT (r=0.4; p=0.038) and BMI (r=0.6; p=0.004). Conclusions SCD promoted changes in lung function and functional capacity, including RVPs and a reduction in the distance walked in the 6MWT when compared to the predictions. In addition, significant correlations between the variables were observed. PMID:24675916

  16. Control of Lung Defense by Mucins and Macrophages: Ancient defense mechanisms with modern functions

    PubMed Central

    Janssen, William J.; Stefanski, Adrianne L.; Bochner, Bruce S.; Evans, Christopher M.

    2016-01-01

    Due to the need to balance the requirement for efficient respiration in the face of tremendous levels of exposure to endogenous and environmental challenges, it is crucial for the lungs to maintain sustainable defense that minimizes damage caused by exposures and the detrimental effects of inflammation to delicate gas exchange surfaces. Accordingly, epithelial and macrophage defenses constitute essential 1st and 2nd lines of protection that prevent the accumulation of potentially harmful agents in the lungs, and under homeostatic conditions do so effectively without inducing inflammation. Though seemingly distinct, recent data show that epithelial and macrophage mediated defenses are linked through their shared reliance on airway mucins, in particular the polymeric mucin MUC5B. This review highlights our understanding of novel mechanisms that link mucus and macrophage defenses. The roles of phagocytosis and the effects of factors that are contained within mucus on phagocytosis, as well as newly identified roles for mucin glycoproteins in the direct regulation of leukocyte functions are discussed. The emergence of this nascent field of glycoimmunobiology sets forth a new paradigm for considering how homeostasis is maintained under healthy conditions and how it is restored in disease. PMID:27587549

  17. Radon exposure mediated changes in lung macrophage morphology and function, in vitro

    SciTech Connect

    Seed, T.M.; Niiro, G.K.; Kretz, N.D.

    1990-01-01

    Bronchopulmonary macrophages play a key role in the normal physiology of the respiratory system. Potential respiratory dysfunctions due to radon/radon daughter exposure-mediated damage of the macrophage lung cell population has been explored via in vitro technology. In this study, macrophages were isolated from lungs of normal healthy dogs by saline lavage, cultured for varying periods (0-96 h) in the presence or absence of radon gas, and assessed for radon dose-dependent changes in cell morphology and function. The in vitro culture procedure and the cell exposing system allowed for detailed alpha particle dosimetry, in relation to the assessed biological end points; i.e. (1) exposure-dependent changes in macrophage surface topography, (2) capacity to elaborate specific growth factor (CSF) essential for self maintenance, and (3) alterations in cell viability. Highlights of the morphologic assessment indicate that relatively low alpha particle doses arising from protracted radon/radon daughter exposure elicites pronounced topographic alterations of the exposed macrophage's cell surface. 27 refs., 7 figs., 1 tab.

  18. Tuberculosis associates with both airflow obstruction and low lung function: BOLD results

    PubMed Central

    Amaral, André F. S.; Coton, Sonia; Kato, Bernet; Tan, Wan C.; Studnicka, Michael; Janson, Christer; Gislason, Thorarinn; Mannino, David; Bateman, Eric D.; Buist, Sonia; Burney, Peter G. J.

    2015-01-01

    Background In small studies and cases series, a history of tuberculosis has been associated with both airflow obstruction, which is characteristic of chronic obstructive pulmonary disease, and restrictive patterns on spirometry. Objective To assess the association between a history of tuberculosis and airflow obstruction and spirometric abnormalities in adults. Methods The study was performed in adults, aged 40 and above, who took part in the multicentre cross-sectional, general population-based, Burden of Obstructive Lung Disease study, had provided acceptable post-bronchodilator spirometry measurements and information on a history of tuberculosis. The associations between a history of tuberculosis and airflow obstruction and spirometric restriction were assessed within each participating centre, and estimates combined using meta-analysis. These estimates were stratified by high and low/middle income countries, according to gross national income. Results A self-reported history of tuberculosis was associated with airflow obstruction (adjusted odds ratio = 2.51, 95% confidence interval 1.83-3.42) and spirometric restriction (adjusted odds ratio = 2.13, 95% confidence interval 1.42-3.19). Conclusion A history of tuberculosis was associated with both airflow obstruction and spirometric restriction, and should be considered as a potentially important cause of obstructive disease and low lung function, particularly where tuberculosis is common. PMID:26113680

  19. Magnetomotive optical coherence elastography for relating lung structure and function in cystic fibrosis

    NASA Astrophysics Data System (ADS)

    Chhetri, Raghav K.; Carpenter, Jerome; Superfine, Richard; Randell, Scott H.; Oldenburg, Amy L.

    2010-02-01

    Cystic fibrosis (CF) is a genetic defect in the cystic fibrosis transmembrane conductance regulator protein and is the most common life-limiting genetic condition affecting the Caucasian population. It is an autosomal recessive, monogenic inherited disorder characterized by failure of airway host defense against bacterial infection, which results in bronchiectasis, the breakdown of airway wall extracellular matrix (ECM). In this study, we show that the in vitro models consisting of human tracheo-bronchial-epithelial (hBE) cells grown on porous supports with embedded magnetic nanoparticles (MNPs) at an air-liquid interface are suitable for long term, non-invasive assessment of ECM remodeling using magnetomotive optical coherence elastography (MMOCE). The morphology of ex vivo CF and normal lung tissues using OCT and correlative study with histology is also examined. We also demonstrate a quantitative measure of normal and CF airway elasticity using MMOCE. The improved understanding of pathologic changes in CF lung structure and function and the novel method of longitudinal in vitro ECM assessment demonstrated in this study may lead to new in vivo imaging and elastography methods to monitor disease progression and treatment in cystic fibrosis.

  20. Pulmonary function tests in the preoperative evaluation of lung cancer surgery candidates. A review of guidelines.

    PubMed

    Trzaska-Sobczak, Marzena; Skoczyński, Szymon; Pierzchała, Władysław

    2014-09-01

    Before planned surgical treatment of lung cancer, the patient's respiratory system function should be evaluated. According to the current guidelines, the assessment should start with measurements of FEV1 (forced expiratory volume in 1 second) and DLco (carbon monoxide lung diffusion capacity). Pneumonectomy is possible when FEV1 and DLco are > 80% of the predicted value (p.v.). If either of these parameters is < 80%, an exercise test with VO2 max (oxygen consumption during maximal exercise) measurement should be performed. When VO2 max is < 35 % p.v. or < 10 ml/kg/min, resection is associated with high risk. If VO2 max is in the range of 35-75% p.v. or 10-20 ml/kg/min, the postoperative values of FEV1 and DLco (ppoFEV1, ppoDLco) should be determined. The exercise test with VO2 max measurement may be replaced with other tests such as the shuttle walk test and the stair climbing test. The distance covered during the shuttle walk test should be > 400 m. Patients considered for lobectomy should be able to climb 3 flights of stairs (12 m) and for pneumonectomy 5 flights of stairs (22 m).

  1. A New Green's Function for the Wake Potential Calculation of the SLAC S-band Constant Gradient Accelerating Section

    SciTech Connect

    Novokhatski, A,; /SLAC

    2012-02-17

    The behavior of the longitudinal wake fields excited by a very short bunch in the SLAC S-band constant gradient accelerating structures has been studied. Wake potential calculations were performed for a bunch length of 10 microns using the author's code to obtain a numerical solution of Maxwell's equations in the time domain. We have calculated six accelerating sections in the series (60-ft) to find the stationary solution. While analyzing the computational results we have found a new formula for the Green's function. Wake potentials, which are calculated using this Green's function are in amazingly good agreement with numerical results over a wide range of bunch lengths. The Green's function simplifies the wake potential calculations and can be easily incorporated into the tracking codes. This is very useful for beam dynamics studies of the linear accelerators of LCLS and FACET.

  2. Short-Term Effects of Fine Particulate Matter and Temperature on Lung Function among Healthy College Students in Wuhan, China

    PubMed Central

    Zhang, Yunquan; He, Mingquan; Wu, Simin; Zhu, Yaohui; Wang, Suqing; Shima, Masayuki; Tamura, Kenji; Ma, Lu

    2015-01-01

    Ambient fine particulate matter (PM) has been associated with impaired lung function, but the effect of temperature on lung function and the potential interaction effect between PM and temperature remain uncertain. To estimate the short-term effects of PM2.5 combined with temperature on lung function, we measured the daily peak expiratory flow (PEF) in a panel of 37 healthy college students in four different seasons. Meanwhile, we also monitored daily concentrations of indoor and outdoor PM2.5 (particulate matter with an aerodynamic diameter ≤2.5 μm), ambient temperature and relative humidity of the study area, where the study participants lived and attended school. Associations of air pollutants and temperature with lung function were assessed by generalized estimating equations (GEEs). A 10 μg/m3 increase of indoor PM2.5 was associated with a change of −2.09 L/min in evening PEF (95%CI: −3.73 L/min–−0.51 L/min) after adjusting for season, height, gender, temperature and relative humidity. The changes of −2.17 L/min (95%CI: −3.81 L/min– −0.52 L/min) and −2.18 L/min (95%CI: −3.96 L/min–−0.41 L/min) in evening PEF were also observed after adjusting for outdoor SO2 and NO2 measured by Environmental Monitoring Center 3 kilometers away, respectively. An increase in ambient temperature was found to be associated with a decrease in lung function and our results revealed a small but significant antagonistic interactive effect between PM2.5 and temperature. Our findings suggest that ambient PM2.5 has an acute adverse effect on lung function in young healthy adults, and that temperature also plays an important role. PMID:26184254

  3. Low-dose AgNPs reduce lung mechanical function and innate immune defense in the absence of cellular toxicity

    PubMed Central

    Botelho, Danielle J.; Leo, Bey Fen; Massa, Christopher B.; Sarkar, Srijata; Tetley, Terry D.; Chung, Kian Fan; Chen, Shu; Ryan, Mary P.; Porter, Alexandra E.; Zhang, Junfeng; Schwander, Stephan K.; Gow, Andrew J.

    2016-01-01

    Multiple studies have examined the direct cellular toxicity of silver nanoparticles (AgNPs). However, the lung is a complex biological system with multiple cell types and a lipid-rich surface fluid; therefore, organ level responses may not depend on direct cellular toxicity. We hypothesized that interaction with the lung lining is a critical determinant of organ level responses. Here, we have examined the effects of low dose intratracheal instillation of AgNPs (0.05 µg/g body weight) 20 and 110nm diameter in size, and functionalized with citrate or polyvinylpyrrolidone. Both size and functionalization were significant factors in particle aggregation and lipid interaction in vitro. One day post-intratracheal instillation lung function was assessed, and bronchoalveolar lavage (BAL) and lung tissue collected. There were no signs of overt inflammation. There was no change in surfactant protein-B content in the BAL but there was loss of surfactant protein-D with polyvinylpyrrolidone (PVP)-stabilized particles. Mechanical impedance data demonstrated a significant increase in pulmonary elastance as compared to control, greatest with 110nm PVP-stabilized particles. Seven days post-instillation of PVP-stabilized particles increased BAL cell counts, and reduced lung function was observed. These changes resolved by 21 days. Hence, AgNP-mediated alterations in the lung lining and mechanical function resolve by 21 days. Larger particles and PVP stabilization produce the largest disruptions. These studies demonstrate that low dose AgNPs elicit deficits in both mechanical and innate immune defense function, suggesting that organ level toxicity should be considered. PMID:26152688

  4. Particulate matter concentration in ambient air and its effects on lung functions among residents in the National Capital Region, India.

    PubMed

    Kesavachandran, C; Pangtey, B S; Bihari, V; Fareed, M; Pathak, M K; Srivastava, A K; Mathur, N

    2013-02-01

    The World Health Organization has estimated that air pollution is responsible for 1.4 % of all deaths and 0.8 % of disability-adjusted life years. NOIDA, located at the National Capital Region, India, was declared as one of the critically air-polluted areas by the Central Pollution Control Board of the Government of India. Studies on the relationship of reduction in lung functions of residents living in areas with higher concentrations of particulate matter (PM) in ambient air were inconclusive since the subjects of most of the studies are hospital admission cases. Very few studies, including one from India, have shown the relationship of PM concentration and its effects of lung functions in the same location. Hence, a cross-sectional study was undertaken to study the effect of particulate matter concentration in ambient air on the lung functions of residents living in a critically air-polluted area in India. PM concentrations in ambient air (PM(1,) PM(2.5)) were monitored at residential locations and identified locations with higher (NOIDA) and lower concentrations (Gurgaon). Lung function tests (FEV(1), PEFR) were conducted using a spirometer in 757 residents. Both air monitoring and lung function tests were conducted on the same day. Significant negative linear relationship exists between higher concentrations of PM(1) with reduced FEV(1) and increased concentrations of PM(2.5) with reduced PEFR and FEV(1). The study shows that reductions in lung functions (PEFR and FEV(1)) can be attributed to higher particulate matter concentrations in ambient air. Decline in airflow obstruction in subjects exposed to high PM concentrations can be attributed to the fibrogenic response and associated airway wall remodeling. The study suggests the intervention of policy makers and stake holders to take necessary steps to reduce the emissions of PM concentrations, especially PM(1,) PM(2.5), which can lead to serious respiratory health concerns in residents.

  5. Low-dose AgNPs reduce lung mechanical function and innate immune defense in the absence of cellular toxicity.

    PubMed

    Botelho, Danielle J; Leo, Bey Fen; Massa, Christopher B; Sarkar, Srijata; Tetley, Terry D; Chung, Kian Fan; Chen, Shu; Ryan, Mary P; Porter, Alexandra E; Zhang, Junfeng; Schwander, Stephan K; Gow, Andrew J

    2016-01-01

    Multiple studies have examined the direct cellular toxicity of silver nanoparticles (AgNPs). However, the lung is a complex biological system with multiple cell types and a lipid-rich surface fluid; therefore, organ level responses may not depend on direct cellular toxicity. We hypothesized that interaction with the lung lining is a critical determinant of organ level responses. Here, we have examined the effects of low dose intratracheal instillation of AgNPs (0.05 μg/g body weight) 20 and 110 nm diameter in size, and functionalized with citrate or polyvinylpyrrolidone. Both size and functionalization were significant factors in particle aggregation and lipid interaction in vitro. One day post-intratracheal instillation lung function was assessed, and bronchoalveolar lavage (BAL) and lung tissue collected. There were no signs of overt inflammation. There was no change in surfactant protein-B content in the BAL but there was loss of surfactant protein-D with polyvinylpyrrolidone (PVP)-stabilized particles. Mechanical impedance data demonstrated a significant increase in pulmonary elastance as compared to control, greatest with 110 nm PVP-stabilized particles. Seven days post-instillation of PVP-stabilized particles increased BAL cell counts, and reduced lung function was observed. These changes resolved by 21 days. Hence, AgNP-mediated alterations in the lung lining and mechanical function resolve by 21 days. Larger particles and PVP stabilization produce the largest disruptions. These studies demonstrate that low dose AgNPs elicit deficits in both mechanical and innate immune defense function, suggesting that organ level toxicity should be considered.

  6. Sleep quality and daytime function in adults with cystic fibrosis and severe lung disease.

    PubMed

    Dancey, D R; Tullis, E D; Heslegrave, R; Thornley, K; Hanly, P J

    2002-03-01

    It was hypothesized that adult cystic fibrosis (CF) patients with severe lung disease have impaired daytime function related to nocturnal hypoxaemia and sleep disruption. Nineteen CF patients (forced expiratory volume in one second 28+/-7% predicted) and 10 healthy subjects completed sleep diaries, overnight polysomnography (PSG), and assessment of daytime sleepiness and neurocognitive function. CF patients tended to report more awakenings (0.7+/-0.5 versus 0.3+/-0.2 x h(-1), p=0.08), and PSG revealed reduced sleep efficiency (71+/-25 versus 93+/-4%, p=0.004) and a higher frequency of awakenings (4.2+/-2.7 versus 2.4+/-1.4 x h(-1), p=0.06). Mean arterial oxygen saturation during sleep was lower in CF patients (84.4+/-6.8 versus 94.3+/-1.5%, p<0.0001) and was associated with reduced sleep efficiency (regression coefficient (r)=0.57, p=0.014). CF patients had short sleep latency on the multiple sleep latency test (6.7+/-3 min). The CF group reported lower levels of activation and happiness and greater levels of fatigue (p<0.01), which correlated with indices of sleep loss, such as sleep efficiency (r=0.47, p=10.05). Objective neurocognitive performance was also impaired in CF patients, reflected by lower throughput for simple addition/subtraction, serial reaction and colour-word conflict. The authors concluded that adult cystic fibrosis patients with severe lung disease have impaired neurocognitive function and daytime sleepiness, which is partly related to chronic sleep loss and nocturnal hypoxaemia.

  7. CCN1 secretion and cleavage regulate the lung epithelial cell functions after cigarette smoke.

    PubMed

    Moon, Hyung-Geun; Kim, Sang-Heon; Gao, Jinming; Quan, Taihao; Qin, Zhaoping; Osorio, Juan C; Rosas, Ivan O; Wu, Min; Tesfaigzi, Yohannes; Jin, Yang

    2014-08-15

    Despite extensive research, the pathogenesis of cigarette smoking (CS)-associated emphysema remains incompletely understood, thereby impeding development of novel therapeutics, diagnostics, and biomarkers. Here, we report a novel paradigm potentially involved in the development of epithelial death and tissue loss in CS-associated emphysema. After prolonged exposure of CS, CCN1 cleavage was detected both in vitro and in vivo. Full-length CCN1 (flCCN1) was secreted in an exosome-shuttled manner, and secreted plasmin converted flCCN1 to cleaved CCN1 (cCCN1) in extracellular matrix. Interestingly, exosome-shuttled flCCN1 facilitated the interleukin (IL)-8 and vascular endothelial growth factor (VEGF) release in response to cigarette smoke extract (CSE). Therefore, flCCN1 potentially promoted CS-induced inflammation via IL-8-mediated neutrophil recruitment and also maintained the lung homeostasis via VEGF secretion. Interestingly, cCCN1 abolished these functions. Furthermore, cCCN1 promoted protease and matrix metalloproteinase (MMP)-1 production after CSE. These effects were mainly mediated by the COOH-terminal fragments of CCN1 after cleavage. Both the decrease of VEGF and the elevation of MMPs favor the development of emphysema. cCCN1, therefore, likely contributes to the epithelial cell damage after CS. Additionally, CSE and cCCN1 both stimulated integrin-α7 expressions in lung epithelial cells. The integrin-α7 appeared to be the binding receptors of cCCN1 and, subsequently, mediated its cellular function by promoting MMP1. Consistent with our observation on the functional roles of cCCN1 in vitro, elevated cCCN1 level was found in the bronchoalveolar lavage fluid from mice with emphysematous changes after 6 mo CS exposure. Taken together, we hypothesize that cCCN1 promoted the epithelial cell death and tissue loss after prolonged CS exposure.

  8. High-Resolution Time-Frequency Spectrum-Based Lung Function Test from a Smartphone Microphone.

    PubMed

    Thap, Tharoeun; Chung, Heewon; Jeong, Changwon; Hwang, Ki-Eun; Kim, Hak-Ryul; Yoon, Kwon-Ha; Lee, Jinseok

    2016-08-17

    In this paper, a smartphone-based lung function test, developed to estimate lung function parameters using a high-resolution time-frequency spectrum from a smartphone built-in microphone is presented. A method of estimation of the forced expiratory volume in 1 s divided by forced vital capacity (FEV₁/FVC) based on the variable frequency complex demodulation method (VFCDM) is first proposed. We evaluated our proposed method on 26 subjects, including 13 healthy subjects and 13 chronic obstructive pulmonary disease (COPD) patients, by comparing with the parameters clinically obtained from pulmonary function tests (PFTs). For the healthy subjects, we found that an absolute error (AE) and a root mean squared error (RMSE) of the FEV₁/FVC ratio were 4.49% ± 3.38% and 5.54%, respectively. For the COPD patients, we found that AE and RMSE from COPD patients were 10.30% ± 10.59% and 14.48%, respectively. For both groups, we compared the results using the continuous wavelet transform (CWT) and short-time Fourier transform (STFT), and found that VFCDM was superior to CWT and STFT. Further, to estimate other parameters, including forced vital capacity (FVC), forced expiratory volume in 1 s (FEV₁), and peak expiratory flow (PEF), regression analysis was conducted to establish a linear transformation. However, the parameters FVC, FEV1, and PEF had correlation factor r values of 0.323, 0.275, and -0.257, respectively, while FEV₁/FVC had an r value of 0.814. The results obtained suggest that only the FEV1/FVC ratio can be accurately estimated from a smartphone built-in microphone. The other parameters, including FVC, FEV1, and PEF, were subjective and dependent on the subject's familiarization with the test and performance of forced exhalation toward the microphone.

  9. High-Resolution Time-Frequency Spectrum-Based Lung Function Test from a Smartphone Microphone

    PubMed Central

    Thap, Tharoeun; Chung, Heewon; Jeong, Changwon; Hwang, Ki-Eun; Kim, Hak-Ryul; Yoon, Kwon-Ha; Lee, Jinseok

    2016-01-01

    In this paper, a smartphone-based lung function test, developed to estimate lung function parameters using a high-resolution time-frequency spectrum from a smartphone built-in microphone is presented. A method of estimation of the forced expiratory volume in 1 s divided by forced vital capacity (FEV1/FVC) based on the variable frequency complex demodulation method (VFCDM) is first proposed. We evaluated our proposed method on 26 subjects, including 13 healthy subjects and 13 chronic obstructive pulmonary disease (COPD) patients, by comparing with the parameters clinically obtained from pulmonary function tests (PFTs). For the healthy subjects, we found that an absolute error (AE) and a root mean squared error (RMSE) of the FEV1/FVC ratio were 4.49% ± 3.38% and 5.54%, respectively. For the COPD patients, we found that AE and RMSE from COPD patients were 10.30% ± 10.59% and 14.48%, respectively. For both groups, we compared the results using the continuous wavelet transform (CWT) and short-time Fourier transform (STFT), and found that VFCDM was superior to CWT and STFT. Further, to estimate other parameters, including forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and peak expiratory flow (PEF), regression analysis was conducted to establish a linear transformation. However, the parameters FVC, FEV1, and PEF had correlation factor r values of 0.323, 0.275, and −0.257, respectively, while FEV1/FVC had an r value of 0.814. The results obtained suggest that only the FEV1/FVC ratio can be accurately estimated from a smartphone built-in microphone. The other parameters, including FVC, FEV1, and PEF, were subjective and dependent on the subject’s familiarization with the test and performance of forced exhalation toward the microphone. PMID:27548164

  10. Preoperative use of incentive spirometry does not affect postoperative lung function in bariatric surgery.

    PubMed

    Cattano, Davide; Altamirano, Alfonso; Vannucci, Andrea; Melnikov, Vladimir; Cone, Chelsea; Hagberg, Carin A

    2010-11-01

    Morbidly obese patients undergoing general anesthesia for laparoscopic bariatric surgery are considered at increased risk of a postoperative decrease in lung function. The purpose of this study was to determine whether a systematic use of incentive spirometry (IS) prior to surgery could help patients to preserve their respiratory function better in the postoperative period. Forty-one morbidly obese (body mass index [BMI] > 40 kg/m²) candidates for laparoscopic bariatric surgery were consented in the study. All patients were taught how to use an incentive spirometer but then were randomized blindly into 2 groups. The control group was instructed to use the incentive spirometer for 3 breaths, once per day. The treatment group was requested to use the incentive spirometer for 10 breaths, 5 times per day. Twenty experimental (mean BMI of 48.9 ± 5.67 kg/m²) and 21 control patients (mean BMI of 48.3 ± 6.96 kg/m²) were studied. The initial mean inspiratory capacity (IC) was 2155 ± 650.08 (SD) cc and 2171 ± 762.98 cc in the experimental and control groups, respectively. On the day of surgery, the mean IC was 2275 ± 777.56 cc versus 2254.76 ± 808.84 cc, respectively. On postoperative day 1, both groups experienced a significant drop of their IC, with volumes of 1458 ± 613.87 cc (t test P < 0.001) and 1557.89 ± 814.67 cc (t test P < 0.010), respectively. Our results suggest that preoperative use of the IS does not lead to significant improvements of inspiratory capacity and that it is a not a useful resource to prevent postoperative decrease in lung function.

  11. EGFR inhibition evokes innate drug resistance in lung cancer cells by preventing Akt activity and thus inactivating Ets-1 function.

    PubMed

    Phuchareon, Janyaporn; McCormick, Frank; Eisele, David W; Tetsu, Osamu

    2015-07-21

    Nonsmall cell lung cancer (NSCLC) is the leading cause of cancer death worldwide. About 14% of NSCLCs harbor mutations in epidermal growth factor receptor (EGFR). Despite remarkable progress in treatment with tyrosine kinase inhibitors (TKIs), only 5% of patients achieve tumor reduction >90%. The limited primary responses are attributed partly to drug resistance inherent in the tumor cells before therapy begins. Recent reports showed that activation of receptor tyrosine kinases (RTKs) is an important determinant of this innate drug resistance. In contrast, we demonstrate that EGFR inhibition promotes innate drug resistance despite blockade of RTK activity in NSCLC cells. EGFR TKIs decrease both the mitogen-activated protein kinase (MAPK) and Akt protein kinase pathways for a short time, after which the Ras/MAPK pathway becomes reactivated. Akt inhibition selectively blocks the transcriptional activation of Ets-1, which inhibits its target gene, dual specificity phosphatase 6 (DUSP6), a negative regulator specific for ERK1/2. As a result, ERK1/2 is activated. Furthermore, elevated c-Src stimulates Ras GTP-loading and activates Raf and MEK kinases. These observations suggest that not only ERK1/2 but also Akt activity is essential to maintain Ets-1 in an active state. Therefore, despite high levels of ERK1/2, Ets-1 target genes including DUSP6 and cyclins D1, D3, and E2 remain suppressed by Akt inhibition. Reduction of DUSP6 in combination with elevated c-Src renews activation of the Ras/MAPK pathway, which enhances cell survival by accelerating Bim protein turnover. Thus, EGFR TKIs evoke innate drug resistance by preventing Akt activity and inactivating Ets-1 function in NSCLC cells.

  12. Lung function measurements over 21 days shiftwork in steelworkers from a strandcasting department.

    PubMed Central

    Nemery, B; Van Leemputten, R; Goemaere, E; Veriter, C; Brasseur, L

    1985-01-01

    On the assumption that short term changes in lung function may reflect the potential for a long term decline the evolution of lung function indices in 25 steelworkers from a strandcasting department and in 11 comparable steelworkers not exposed to dust was investigated over an almost uninterrupted 21 day working period and over three different workshifts. The mean total dust level in the strandcasting department, assessed by personal sampling, was 11.8 mg/m3. All subjects were examined at the beginning, in the middle, and at the end of their first (day 1) morning shift (0600 to 1400), their last (day 14) afternoon shift (1400 to 2200), and their last (day 21) night shift (2200 to 0600). Indices measured were vital capacity (VC), forced expiratory volume in one second (FEV1) and in three seconds (FEV3), forced expiratory flow over the middle half of the forced vital capacity (FEF25-75), peak expiratory flow rate (PEFR), the slope of the N2 plateau (delta N2) and the closing volume (CV) of the single breath oxygen test. Differences in indices between initial values (0600 on day 1) and final values (0500 on day 21) were not significant in the control group (except delta N2 which became lower); in the casting group there were significant (p less than 0.05) decreases in FEF25-75 and FEV3, but these decreases were not significantly greater than in the control group. Lung function changes were not significant in either group over the morning shift. During the afternoon there were significant decreases in spirometric indices in the casting group, with no significant decreases in the control group, but the interactions between exposure and time were generally not significant. During the night shift, however, the decreases in FEV1 and FEF25-75 observed in the strandcasting group were significantly more pronounced than in the control group. The single breath test, which many subjects failed to perform correctly on each occasion, showed no significant changes in closing

  13. Ambient air pollution, lung function and airway responsiveness in children with asthma

    PubMed Central

    Ierodiakonou, Despo; Zanobetti, Antonella; Coull, Brent A.; Melly, Steve; Postma, Dirkje S.; Boezen, H. Marike; Vonk, Judith M.; Williams, Paul V.; Shapiro, Gail G.; McKone, Edward F.; Hallstrand, Teal S.; Koenig, Jane Q.; Schildcrout, Jonathan S.; Lumley, Thomas; Fuhlbrigge, Anne N.; Koutrakis, Petros; Schwartz, Joel; Weiss, Scott T.; Gold, Diane R

    2016-01-01

    Background Although ambient air pollution has been linked to reduced lung function in healthy children, longitudinal analyses of pollution effects in asthma are lacking. Objective To investigate pollution effects in a longitudinal asthma study and effect modification by controller medications. Methods We examined associations of lung function and methacholine responsiveness (PC20) with ozone, carbon monoxide (CO), nitrogen dioxide (NO2) and sulfur dioxide (SO2) levels in 1,003 asthmatic children participating in a 4-year clinical trial. We further investigated whether budesonide and nedocromil modified pollution effects. Daily pollutant concentrations were linked to zip/postal code of residence. Linear mixed models tested associations of within-subject pollutant concentrations with FEV1 and FVC %predicted, FEV1/FVC and PC20, adjusting for seasonality and confounders. Results Same-day and 1-week average CO levels were negatively associated with post-bronchodilator %predicted FEV1 (change(95%CI) per IQR: −0.33(−0.49, −0.16), −0.41(−0.62, −0.21), respectively) and FVC (−0.19(−0.25, −0.07), −0.25(−0.43, −0.07)). Longer-term four-month averages of CO were negatively associated with prebronchodilator %predicted FEV1 and FVC (−0.36(−0.62, −0.10), −0.21(−0.42, −0.01)). Four-month averaged CO and ozone levels were negatively associated with FEV1/FVC (p<0.05). Increased four-month average NO2 levels were associated with reduced post-bronchodilator FEV1 and FVC %predicted. Long-term exposures to SO2 were associated with reduced PC20 (%change(95%CI) per IQR:-6(-11,-1.5)). Treatment augmented the negative short-term CO effect on PC20. Conclusions Air pollution adversely influences lung function and PC20 in asthmatic children. Treatment with controller medications may not protect but worsens the CO effects on PC20. This clinical trial design evaluates modification of pollution effects by treatment without confounding by indication. PMID

  14. Glucagon-like peptide-1 (GLP-1) reduces mortality and improves lung function in a model of experimental obstructive lung disease in female mice.

    PubMed

    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 < .001). Survival proportions were significantly increased in GLP-1R agonist-treated mice (P < .01). SFTPB and SFTPA were down-regulated and the expression of inflammatory cytokines were increased in mice with obstructive lung disease, but levels were largely unaffected by GLP-1R 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.

  15. Assessment of the setup dependence of detector response functions for mega-voltage linear accelerators

    SciTech Connect

    Fox, Christopher; Simon, Tom; Simon, Bill; Dempsey, James F.; Kahler, Darren; Palta, Jatinder R.; Liu Chihray; Yan Guanghua

    2010-02-15

    Purpose: Accurate modeling of beam profiles is important for precise treatment planning dosimetry. Calculated beam profiles need to precisely replicate profiles measured during machine commissioning. Finite detector size introduces perturbations into the measured profiles, which, in turn, impact the resulting modeled profiles. The authors investigate a method for extracting the unperturbed beam profiles from those measured during linear accelerator commissioning. Methods: In-plane and cross-plane data were collected for an Elekta Synergy linac at 6 MV using ionization chambers of volume 0.01, 0.04, 0.13, and 0.65 cm{sup 3} and a diode of surface area 0.64 mm{sup 2}. The detectors were orientated with the stem perpendicular to the beam and pointing away from the gantry. Profiles were measured for a 10x10 cm{sup 2} field at depths ranging from 0.8 to 25.0 cm and SSDs from 90 to 110 cm. Shaping parameters of a Gaussian response function were obtained relative to the Edge detector. The Gaussian function was deconvolved from the measured ionization chamber data. The Edge detector profile was taken as an approximation to the true profile, to which deconvolved data were compared. Data were also collected with CC13 and Edge detectors for additional fields and energies on an Elekta Synergy, Varian Trilogy, and Siemens Oncor linear accelerator and response functions obtained. Response functions were compared as a function of depth, SSD, and detector scan direction. Variations in the shaping parameter were introduced and the effect on the resulting deconvolution profiles assessed. Results: Up to 10% setup dependence in the Gaussian shaping parameter occurred, for each detector for a particular plane. This translated to less than a {+-}0.7 mm variation in the 80%-20% penumbral width. For large volume ionization chambers such as the FC65 Farmer type, where the cavity length to diameter ratio is far from 1, the scan direction produced up to a 40% difference in the shaping

  16. Long-term effects of severe acute malnutrition on lung function in Malawian children: a cohort study.

    PubMed

    Lelijveld, Natasha; Kerac, Marko; Seal, Andrew; Chimwezi, Emmanuel; Wells, Jonathan C; Heyderman, Robert S; Nyirenda, Moffat J; Stocks, Janet; Kirkby, Jane

    2017-04-01

    Early nutritional insults may increase risk of adult lung disease. We aimed to quantify the impact of severe acute malnutrition (SAM) on spirometric outcomes 7 years post-treatment and explore predictors of impaired lung function.Spirometry and pulse oximetry were assessed in 237 Malawian children (median age: 9.3 years) who had been treated for SAM and compared with sibling and age/sex-matched community controls. Spirometry results were expressed as z-scores based on Global Lung Function Initiative reference data for the African-American population.Forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were low in all groups (mean FEV1 z-score: -0.47 for cases, -0.48 for siblings, -0.34 for community controls; mean FVC z-score: -0.32, -0.38, and -0.15 respectively). There were no differences in spirometric or oximetry outcomes between SAM survivors and controls. Leg length was shorter in SAM survivors but inter-group sitting heights were similar. HIV positive status or female sex was associated with poorer FEV1, by 0.55 and 0.31 z-scores, respectively.SAM in early childhood was not associated with subsequent reduced lung function compared to local controls. Preservation of sitting height and compromised leg length suggest "thrifty" or "lung-sparing" growth. Female sex and HIV positive status were identified as potentially high-risk groups.

  17. Loss of Dnmt3b function upregulates the tumor modifier Ment and accelerates mouse lymphomagenesis.

    PubMed

    Hlady, Ryan A; Novakova, Slavomira; Opavska, Jana; Klinkebiel, David; Peters, Staci L; Bies, Juraj; Hannah, Jay; Iqbal, Javeed; Anderson, Kristi M; Siebler, Hollie M; Smith, Lynette M; Greiner, Timothy C; Bastola, Dhundy; Joshi, Shantaram; Lockridge, Oksana; Simpson, Melanie A; Felsher, Dean W; Wagner, Kay-Uwe; Chan, Wing C; Christman, Judith K; Opavsky, Rene

    2012-01-01

    DNA methyltransferase 3B (Dnmt3b) belongs to a family of enzymes responsible for methylation of cytosine residues in mammals. DNA methylation contributes to the epigenetic control of gene transcription and is deregulated in virtually all human tumors. To better understand the generation of cancer-specific methylation patterns, we genetically inactivated Dnmt3b in a mouse model of MYC-induced lymphomagenesis. Ablation of Dnmt3b function using a conditional knockout in T cells accelerated lymphomagenesis by increasing cellular proliferation, which suggests that Dnmt3b functions as a tumor suppressor. Global methylation profiling revealed numerous gene promoters as potential targets of Dnmt3b activity, the majority of which were demethylated in Dnmt3b-/- lymphomas, but not in Dnmt3b-/- pretumor thymocytes, implicating Dnmt3b in maintenance of cytosine methylation in cancer. Functional analysis identified the gene Gm128 (which we termed herein methylated in normal thymocytes [Ment]) as a target of Dnmt3b activity. We found that Ment was gradually demethylated and overexpressed during tumor progression in Dnmt3b-/- lymphomas. Similarly, MENT was overexpressed in 67% of human lymphomas, and its transcription inversely correlated with methylation and levels of DNMT3B. Importantly, knockdown of Ment inhibited growth of mouse and human cells, whereas overexpression of Ment provided Dnmt3b+/+ cells with a proliferative advantage. Our findings identify Ment as an enhancer of lymphomagenesis that contributes to the tumor suppressor function of Dnmt3b and suggest it could be a potential target for anticancer therapies.

  18. Accelerated telomere erosion is associated with a declining immune function of caregivers of Alzheimer's disease patients.

    PubMed

    Damjanovic, Amanda K; Yang, Yinhua; Glaser, Ronald; Kiecolt-Glaser, Janice K; Nguyen, Huy; Laskowski, Bryon; Zou, Yixiao; Beversdorf, David Q; Weng, Nan-ping

    2007-09-15

    Caregivers of Alzheimer's disease patients endure chronic stress associated with a decline of immune function. To assess the psychological and immunological changes of caregivers, we compared depressive symptoms, PBMC composition, in vitro activation-induced proliferation and cytokine production, and telomere length and telomerase activity of 82 individuals (41 caregivers and 41 age- and gender-matched controls). We found depressive symptoms were significantly higher in caregivers than in controls (p < 0.001). Correspondingly, caregivers had significantly lower T cell proliferation but higher production of immune-regulatory cytokines (TNF-alpha and IL-10) than controls in response to stimulation in vitro. We examined the impact of these changes on cellular replicative lifespan and found that caregivers had significantly shorter telomere lengths in PBMC than controls (6.2 and 6.4 kb, respectively, p < 0.05) with similar shortening in isolated T cells and monocytes and that this telomere attrition in caregivers was not due to an increase of shorter telomere possessing T cell subsets in PBMC. Finally, we showed that basal telomerase activity in PBMC and T cells was significantly higher in caregivers than in controls (p < 0.0001), pointing to an unsuccessful attempt of cells to compensate the excessive loss of telomeres in caregivers. These findings demonstrate that chronic stress is associated with altered T cell function and accelerated immune cell aging as suggested by excessive telomere loss.

  19. Giving feedback in medical teaching: a case of lung function laboratory/spirometry.

    PubMed

    Meo, Sultan Ayoub

    2013-01-01

    Feedback in medical teaching is an important part of medical education, it encourages and enhances the learners' knowledge, skills and professional performance at various stages of their schooling. A constructive feedback enhances the awareness of strength and areas for improvement. An adequate, meaningful and fruitful feedback needs motivation, emphasis, objectivity, expertise, and active participation in the session. Before giving feedback, the instructor should be well prepared and must have practice on the task. The instructor should utilize all means such as good oral presentation, eye contact, visual cues, utilize body language to actively involve the learners in a session, all these activities enhance the knowledge, skill and attitude of the learners. The aim of this commentary is to highlight the basic issues in giving an appropriate feedback in medical teaching with special emphasis on a lung function laboratory / Spirometry.

  20. Sixteen new lung function signals identified through 1000 Genomes Project reference panel imputation.

    PubMed

    Soler Artigas, María; Wain, Louise V; Miller, Suzanne; Kheirallah, Abdul Kader; Huffman, Jennifer E; Ntalla, Ioanna; Shrine, Nick; Obeidat, Ma'en; Trochet, Holly; McArdle, Wendy L; Alves, Alexessander Couto; Hui, Jennie; Zhao, Jing Hua; Joshi, Peter K; Teumer, Alexander; Albrecht, Eva; Imboden, Medea; Rawal, Rajesh; Lopez, Lorna M; Marten, Jonathan; Enroth, Stefan; Surakka, Ida; Polasek, Ozren; Lyytikäinen, Leo-Pekka; Granell, Raquel; Hysi, Pirro G; Flexeder, Claudia; Mahajan, Anubha; Beilby, John; Bossé, Yohan; Brandsma, Corry-Anke; Campbell, Harry; Gieger, Christian; Gläser, Sven; González, Juan R; Grallert, Harald; Hammond, Chris J; Harris, Sarah E; Hartikainen, Anna-Liisa; Heliövaara, Markku; Henderson, John; Hocking, Lynne; Horikoshi, Momoko; Hutri-Kähönen, Nina; Ingelsson, Erik; Johansson, Åsa; Kemp, John P; Kolcic, Ivana; Kumar, Ashish; Lind, Lars; Melén, Erik; Musk, Arthur W; Navarro, Pau; Nickle, David C; Padmanabhan, Sandosh; Raitakari, Olli T; Ried, Janina S; Ripatti, Samuli; Schulz, Holger; Scott, Robert A; Sin, Don D; Starr, John M; Viñuela, Ana; Völzke, Henry; Wild, Sarah H; Wright, Alan F; Zemunik, Tatijana; Jarvis, Deborah L; Spector, Tim D; Evans, David M; Lehtimäki, Terho; Vitart, Veronique; Kähönen, Mika; Gyllensten, Ulf; Rudan, Igor; Deary, Ian J; Karrasch, Stefan; Probst-Hensch, Nicole M; Heinrich, Joachim; Stubbe, Beate; Wilson, James F; Wareham, Nicholas J; James, Alan L; Morris, Andrew P; Jarvelin, Marjo-Riitta; Hayward, Caroline; Sayers, Ian; Strachan, David P; Hall, Ian P; Tobin, Martin D

    2015-12-04

    Lung function measures are used in the diagnosis of chronic obstructive pulmonary disease. In 38,199 European ancestry individuals, we studied genome-wide association of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC with 1000 Genomes Project (phase 1)-imputed genotypes and followed up top associations in 54,550 Europeans. We identify 14 novel loci (P<5 × 10(-8)) in or near ENSA, RNU5F-1, KCNS3, AK097794, ASTN2, LHX3, CCDC91, TBX3, TRIP11, RIN3, TEKT5, LTBP4, MN1 and AP1S2, and two novel signals at known loci NPNT and GPR126, providing a basis for new understanding of the genetic determinants of these traits and pulmonary diseases in which they are altered.