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Sample records for accelerated lung function

  1. 27-Hydroxycholesterol accelerates cellular senescence in human lung resident cells.

    PubMed

    Hashimoto, Yuichiro; Sugiura, Hisatoshi; Togo, Shinsaku; Koarai, Akira; Abe, Kyoko; Yamada, Mitsuhiro; Ichikawa, Tomohiro; Kikuchi, Takashi; Numakura, Tadahisa; Onodera, Katsuhiro; Tanaka, Rie; Sato, Kei; Yanagisawa, Satoru; Okazaki, Tatsuma; Tamada, Tsutomu; Kikuchi, Toshiaki; Hoshikawa, Yasushi; Okada, Yoshinori; Ichinose, Masakazu

    2016-06-01

    Cellular senescence is reportedly involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). We previously showed that 27-hydroxycholesterol (27-OHC) is elevated in the airways of COPD patients compared with those in healthy subjects. The aim of this study was to investigate whether lung fibroblasts of COPD patients are senescent and to determine the effects of 27-OHC on senescence of lung resident cells, including fibroblasts and airway epithelial cells. Localization of senescence-associated proteins and sterol 27-hydroxylase was investigated in the lungs of COPD patients by immunohistochemical staining. To evaluate whether 27-OHC accelerates cellular senescence, lung resident cells were exposed to 27-OHC. Senescence markers and fibroblast-mediated tissue repair were investigated in the 27-OHC-treated cells. Expression of senescence-associated proteins was significantly enhanced in lung fibroblasts of COPD patients. Similarly, expression of sterol 27-hydroxylase was significantly upregulated in lung fibroblasts and alveolar macrophages in these patients. Treatment with the concentration of 27-OHC detected in COPD airways significantly augmented expression of senescence-associated proteins and senescence-associated β-galactosidase activity, and delayed cell growth through the prostaglandin E2-reactive nitrogen species pathway. The 27-OHC-treated fibroblasts impaired tissue repair function. Fibroblasts from lungs of COPD patients showed accelerated senescence and were more susceptible to 27-OHC-induced cellular senescence compared with those of healthy subjects. In conclusion, 27-OHC accelerates cellular senescence in lung resident cells and may play a pivotal role in cellular senescence in COPD. PMID:27036870

  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. PMID:24477002

  3. 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.

  4. [Lung cancer in elderly patients: lung cancer and lung function].

    PubMed

    Tanita, Tatsuo

    2005-07-01

    The incidence of bronchogenic carcinoma is increasing as life expectancy rises. With increase in the aged population in Japan, the number of patients suffering from lung cancer and candidates for lung resections are increasing. In this paper, the author lists up indispensable procedures for diagnosis, namely, lung function tests, unilateral pulmonary arterial occlusion test and exercise tolerance test. The cut-offs for identifying candidates for elderly patients for lung resections can be applied the same cut-offs for younger patients. Also the author indicates the importance of postoperative management for lung lobe resections. In order to prevent postoperative problems such as congestive heart failure that might be a fetal complication, the most useful check values after the lung surgery for elderly patients are rate of transfusion and urine volume. In conclusion, when elderly patients assert their rights to undergo lung surgery, we, the thoracic surgeons, should reply their requests under the equal quality of safe surgery as that for younger patients. Besides, it is desirable that even elderly patients, over 80 years old, who undergo lung surgery should guarantee their quality of daily life after surgery.

  5. Lung function and airway diseases.

    PubMed

    Weiss, Scott T

    2010-01-01

    Two studies report genome-wide association studies for lung function, using cross-sectional spirometric measurements in healthy individuals. They identify six genetic loci newly associated to natural variation in lung function, which may have implications for the related airway diseases of asthma and chronic obstructive pulmonary disease. PMID:20037613

  6. 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

  7. Regulatory T Cell DNA Methyltransferase Inhibition Accelerates Resolution of Lung Inflammation

    PubMed Central

    Singer, Benjamin D.; Mock, Jason R.; Aggarwal, Neil R.; Garibaldi, Brian T.; Sidhaye, Venkataramana K.; Florez, Marcus A.; Chau, Eric; Gibbs, Kevin W.; Mandke, Pooja; Tripathi, Ashutosh; Yegnasubramanian, Srinivasan; King, Landon S.

    2015-01-01

    Acute respiratory distress syndrome (ARDS) is a common and often fatal inflammatory lung condition without effective targeted therapies. Regulatory T cells (Tregs) resolve lung inflammation, but mechanisms that enhance Tregs to promote resolution of established damage remain unknown. DNA demethylation at the forkhead box protein 3 (Foxp3) locus and other key Treg loci typify the Treg lineage. To test how dynamic DNA demethylation affects lung injury resolution, we administered the DNA methyltransferase inhibitor 5-aza-2′-deoxycytidine (DAC) to wild-type (WT) mice beginning 24 hours after intratracheal LPS-induced lung injury. Mice that received DAC exhibited accelerated resolution of their injury. Lung CD4+CD25hiFoxp3+ Tregs from DAC-treated WT mice increased in number and displayed enhanced Foxp3 expression, activation state, suppressive phenotype, and proliferative capacity. Lymphocyte-deficient recombinase activating gene-1–null mice and Treg-depleted (diphtheria toxin-treated Foxp3DTR) mice did not resolve their injury in response to DAC. Adoptive transfer of 2 × 105 DAC-treated, but not vehicle-treated, exogenous Tregs rescued Treg-deficient mice from ongoing lung inflammation. In addition, in WT mice with influenza-induced lung inflammation, DAC rescue treatment facilitated recovery of their injury and promoted an increase in lung Treg number. Thus, DNA methyltransferase inhibition, at least in part, augments Treg number and function to accelerate repair of experimental lung injury. Epigenetic pathways represent novel manipulable targets for the treatment of ARDS. PMID:25295995

  8. 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

  9. What Are Lung Function Tests?

    MedlinePlus

    ... COPD How the Lungs Work Idiopathic Pulmonary Fibrosis Sarcoidosis Send a link to NHLBI to someone by ... caused by conditions such as pulmonary fibrosis and sarcoidosis (sar-koy-DOE-sis). Also, these tests might ...

  10. Function of Proton Channels in Lung Epithelia.

    PubMed

    Fischer, Horst

    2012-05-01

    The properties of the voltage-dependent H(+) channel have been studied in lung epithelial cells for many years, and recently HVCN1 mRNA expression has been linked directly to H(+) channel function in lung epithelium. The H(+) channel is activated by strong membrane depolarization, intracellular acidity, or extracellular alkalinity. Early on it was noted that these are surprising physiological channel characteristics when considering that lung epithelial cells have rather stable membrane potentials and a well pH-buffered intracellular milieu. This raised the question under which conditions the H(+) channel is active in lung epithelium and what is its physiological function there. Current understanding of the HVCN1 H(+) channel in lung epithelial acid secretion, its activation by an alkaline mucosal extracellular pH, and its role in the regulation of the mucosal pH of the lung has resulted in a model of mucosal pH regulation based on the parallel function of the HVCN1 H(+) channel and the CFTR HCO(3) (-) channel, which suggests that HVCN1 is a critical factor that maintains a neutral surface pH in the lung.

  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. Particulate air pollution and impaired lung function.

    PubMed

    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

  13. Particulate air pollution and impaired lung function.

    PubMed

    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.

  14. Monocyte interaction accelerates HCl-induced lung epithelial remodeling

    PubMed Central

    2014-01-01

    Background Acute respiratory distress syndrome (ARDS) is characterized by overwhelming inflammatory responses and lung remodeling. We hypothesized that leukocyte infiltration during the inflammatory response modulates epithelial remodeling through a mechanism of epithelial-mesenchymal transition (EMT). Methods Human lung epithelial cells were treated for 30 min with hydrochloric acid (HCl). Human monocytes were then cocultured with the epithelial cells for up to 48 h, in the presence or absence of blocking peptides against lymphocyte function-associated antigen-1 (LFA-1), or tyrphostin A9, a specific inhibitor for platelet-derived growth factor (PDGF) receptor tyrosine kinase. Results Exposure of lung epithelial cells to HCl resulted in increased expression of intercellular adhesion molecule-1 (ICAM-1) and production of interleukin (IL)-8 at 24 h. The expression of the epithelial markers E-cadherin decreased while the mesenchymal markers vimentin and α-smooth muscle actin (α-SMA) increased at 24 h and remained high at 48 h. The addition of monocytes augmented the profiles of lower expression of epithelial markers and higher mesenchymal markers accompanied by increased collagen deposition. This EMT profile was associated with an enhanced production of IL-8 and PDGF. Treatment of the lung epithelial cells with the LAF-1 blocking peptides CD11a237–246 or/and CD18112–122 suppressed monocyte adhesion, production of IL-8, PDGF and hydroxyproline as well as EMT markers. Treatment with tyrphostin A9 prevented the EMT profile shift induced by HCl stimulation. Conclusions The interaction between epithelial cells and monocytes enhanced epithelial remodelling after initial injury through EMT signalling that is associated with the release of soluble mediators, including IL-8 and PDGF. PMID:25108547

  15. Immunological Priming Requires Tregs and Interleukin-10-Producing Macrophages to Accelerate Resolution from Severe Lung Inflammation

    PubMed Central

    Eto, Yoshiki; Tripathi, Ashutosh; Mandke, Pooja; Mock, Jason R.; Garibaldi, Brian T.; Singer, Benjamin D.; Sidhaye, Venkataramana K.; Horton, Maureen R.; King, Landon S.; D'Alessio, Franco R.

    2014-01-01

    Overwhelming lung inflammation frequently occurs following exposure to both direct infectious and non-infectious agents, and is a leading cause of mortality world-wide. In that context, immunomodulatory strategies may be utilized to limit severity of impending organ damage. We sought to determine whether priming the lung by activating the immune system, or immunological priming, could accelerate resolution of severe lung inflammation. We assessed the importance of alveolar macrophages, regulatory T cells, and their potential interaction during immunological priming. We demonstrate that oropharyngeal delivery of low-dose lipopolysaccharide can immunologically prime the lung to augment alveolar macrophage production of interleukin-10 and enhance resolution of lung inflammation induced by a lethal dose of lipopolysaccharide or by pseudomonas bacterial pneumonia. Interleukin-10 deficient mice did not achieve priming and were unable to accelerate lung injury resolution. Depletion of lung macrophages or regulatory T cells during the priming response completely abrogated the positive effect of immunological priming on resolution of lung inflammation and significantly reduced alveolar macrophage interleukin-10 production. Finally, we demonstrated that oropharyngeal delivery of synthetic CpG-oligonucleotides elicited minimal lung inflammation compared to low-dose lipopolysaccharide, but nonetheless primed the lung to accelerate resolution of lung injury following subsequent lethal lipopolysaccharide exposure. Immunological priming is a viable immunomodulatory strategy used to enhance resolution in an experimental acute lung injury model with the potential for therapeutic benefit against a wide array of injurious exposures. PMID:24688024

  16. Imaging Phenotype of Occupational Endotoxin-Related Lung Function Decline

    PubMed Central

    Lai, Peggy S.; Hang, Jing-qing; Zhang, Feng-ying; Sun, J.; Zheng, Bu-Yong; Su, Li; Washko, George R.; Christiani, David C.

    2016-01-01

    accelerated lung function decline. Citation: Lai PS, Hang J, Zhang F, Sun J, Zheng BY, Su L, Washko GR, Christiani DC. 2016. Imaging phenotype of occupational endotoxin-related lung function decline. Environ Health Perspect 124:1436–1442; http://dx.doi.org/10.1289/EHP195 PMID:27138294

  17. Aerosol-derived lung morphometry: comparisons with a lung model and lung function indexes.

    PubMed

    Blanchard, J D; Heyder, J; O'Donnell, C R; Brain, J D

    1991-10-01

    This study evaluated the ability of aerosol-derived lung morphometry to noninvasively probe airway and acinar dimensions. Effective air-space diameters (EAD) were calculated from the time-dependent gravitational losses of 1-microns particles from inhaled aerosol boluses during breath holding. In 17 males [33 +/- 7 (SD) yr] the relationship between EAD and volumetric penetration of the bolus into the lungs (Vp) could be expressed by the linear power-law function, log (EAD) alpha beta log (Vp). Our EAD values were consistent with Weibel's symmetric lung model A for small airways and more distal air spaces. As lung volume increased from 57 to 87% of total lung capacity (TLC), EAD at Vp of 160 and 550 cm3 increased 70 and 41%, respectively. At 57% TLC, log (EAD) at 160 cm3 was significantly correlated with airway resistance (r = -0.57, P less than 0.0204) but not with forced expired flow between 25 and 75% of vital capacity. Log (EAD) at 400 cm3 was correlated with deposition of 1-micron particles (r = -0.73, P less than 0.0009). We conclude that aerosol-derived lung morphometry is a responsive noninvasive probe of peripheral air-space diameters. PMID:1757343

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

    SciTech Connect

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

    2011-10-01

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

  19. Lung function after bone marrow grafting

    SciTech Connect

    Depledge, M.H.; Barrett, A.; Powles, R.L.

    1983-02-01

    Results of a prospective lung function study are presented for 48 patients with acute myeloid leukemia (AML) treated with total body irradiation (TBI) and bone marrow transplantation (BMT) at the Royal Marsden Hospital between 1978 and 1980. Patients with active disease or who were in remission following cytoreductive chemotherapy had mildly impaired gas exchange prior to grafting. After TBI and BMT all patients studied developed progressive deterioration of lung function during the first 100 days, although these changes were subclinical. Infection and graft-versus-host disease (GvHD) were associated with further worsening of restrictive ventilatory defects and diffusing capacity (D/sub L/CO). Beyond 100 days, ventilatory ability returned to normal and gas transfer improved, although it failed to reach pre-transplant levels. There was no evidence of progressive pulmonary fibrosis during the first year after grafting.

  20. 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

  1. 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

  2. Lung function: occupational exposure to wood dust

    PubMed Central

    2009-01-01

    Objectives Occupational exposure to wood dust has been shown to cause several respiratory disorders, such as allergic rhinitis, chronic bronchitis, asthma, sino-nasal adenocarcinoma, and impairment of lung function. The aim of the study was to estimate lung function (in the woodworking industry) among workers employed by wood processing, who run the risk of being expose to wood dust. Methods The study concerns a group of 70 workers aged 24-55. All the workers underwent general and laryngological examination. A group of 20 workers, working at the positions where dustiness exceeded TLV (threshold limit value) took X-ray of the chest and spirometry. The following parameters were measured: VC, IC, ERV, TV, BF, FEV1, FVC, PEF, MEF25-75, FEV1%FVC, FEV1%VC. The data are presented as means ± SD and the authors applied references values according to ERS guidelines. Results The results show that there was no decline in FEV1 (3.7 ± 0.7) and FVC (4.5 ± 0.8). Normal lung function was defined as FEV1/VC ratio ≥0.7. None of the tested workers had obstructive pattern in spirometry. The mean FEV1%VC was 77.1 ± 10.2. These results suggest that wood dust exposure might not lead to significant pulmonary damage. Conclusions These data do not corroborate that wood dust plays significant role in lung function impairment. Future studies of respiratory health among workers exposed to wood dust are needed. PMID:20156717

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. Perinatal lung function and invasive antenatal procedures

    PubMed Central

    Yuksel, B.; Greenough, A.; Naik, S.; Cheeseman, P.; Nicolaides, K. H.

    1997-01-01

    BACKGROUND: Second trimester amniocentesis has been associated with an excess of perinatal lung function abnormalities. Early amniocentesis might have a similar adverse effect, as could other invasive investigations carried out in the first trimester. METHODS: Plethysmographic measurements of thoracic gas volume (TGV) and airway resistance (Raw), from which specific conductance (sGaw) was calculated, were made in the perinatal period in non-sedated infants. In addition, functional residual capacity (FRC) was measured using a helium gas dilution technique. Measurements were made in 47 infants whose mothers had undergone early amniocentesis, 19 whose mothers had undergone chorion villus sampling, and 25 controls whose mothers had undergone no invasive antenatal procedures. RESULTS: The infants of mothers who had undergone early amniocentesis had higher TGV (95% CI - 6.3 to 1.1 ml/kg) and Raw values (95% CI -10.68 to -5.23 cm H2O/l/s) and lower sGaw (0.11 to 0.84 l/cm H2O.s) and FRC (-5.17 to - 0.87 ml/kg) values than the controls. Infants whose mothers had undergone chorion villus sampling also differed significantly from the controls with higher Raw (-7.59 to -1.99 cm H2O/l/s) and lower sGaw values (0.11 to 0.24 l/cm H2O.s), and had lower Raw values than those in the early amniocentesis group (not significant). Logistic regression analysis, taking into account possible risk factors for abnormal lung function, showed that the procedures performed in the first trimester were independently associated with a high airways resistance. CONCLUSION: These results suggest that invasive procedures performed in the first trimester of pregnancy have an adverse effect on perinatal lung function. 


 PMID:9059482

  8. Temporal pattern of accelerated lung growth after tracheal occlusion in the fetal rabbit.

    PubMed Central

    De Paepe, M. E.; Johnson, B. D.; Papadakis, K.; Sueishi, K.; Luks, F. I.

    1998-01-01

    Tracheal occlusion in utero is a potent stimulus of fetal lung growth. We describe the early growth mechanics of fetal lungs and type II pneumocytes after tracheal ligation (TL). Fetal rabbits underwent TL at 24 days gestational age (DGA; late pseudoglandular stage; term = 31 to 33 days) and were sacrificed at time intervals ranging from 1 to 5 days after TL. Lung growth was measured by stereological volumetry and bromodeoxyuridine (BrdU) pulse labeling. Pneumocyte II population kinetics were analyzed using a combination of anti-surfactant protein A and BrdU immunohistochemistry and computer-assisted morphometry. Nonoperated littermates served as controls. TL resulted in dramatically enhanced lung growth (lung weight/body weight was 5.00 +/- 0.81% in TL versus 2.52 +/- 0.13% in controls at 29 DGA; P < 0.001, unpaired Student's t-test). Post-TL lung growth was characterized by a 3-day lag-phase typified by relative stagnation of growth, followed by distension of airspaces, increased cell proliferation, and accelerated architectural and cellular maturation by postligation days 4 and 5. During the proliferation phase, the replicative activity of type II cells was markedly increased (type II cell BrdU labeling index was 10.0 +/- 4.1% in TL versus 1.1 +/- 0.3% for controls at 29 DGA; P < 0.02), but their numerical density decreased (3.0 +/- 0.5 x 10(-3)/microm2 in TL versus 4.5 +/- 0.3 x 10(-3)/microm2 in controls at 29 DGA; P < 0.02), suggesting accelerated terminal differentiation to type I cells. In conclusion, post-TL lung development is characterized by a well defined temporal pattern of lung growth and maturation. The rabbit model lends itself well to study the regulatory mechanisms underlying accelerated fetal lung growth after TL. Images Figure 2 Figure 4 Figure 6 Figure 8 Figure 9 PMID:9422535

  9. Pre-operative optimisation of lung function

    PubMed Central

    Azhar, Naheed

    2015-01-01

    The anaesthetic management of patients with pre-existing pulmonary disease is a challenging task. It is associated with increased morbidity in the form of post-operative pulmonary complications. Pre-operative optimisation of lung function helps in reducing these complications. Patients are advised to stop smoking for a period of 4–6 weeks. This reduces airway reactivity, improves mucociliary function and decreases carboxy-haemoglobin. The widely used incentive spirometry may be useful only when combined with other respiratory muscle exercises. Volume-based inspiratory devices have the best results. Pharmacotherapy of asthma and chronic obstructive pulmonary disease must be optimised before considering the patient for elective surgery. Beta 2 agonists, inhaled corticosteroids and systemic corticosteroids, are the main drugs used for this and several drugs play an adjunctive role in medical therapy. A graded approach has been suggested to manage these patients for elective surgery with an aim to achieve optimal pulmonary function. PMID:26556913

  10. Effect of backpack fit on lung function.

    PubMed

    Bygrave, S; Legg, S J; Myers, S; Llewellyn, M

    2004-02-26

    Carrying loads close to the trunk with a backpack causes a restrictive type of change in lung function in which Forced Vital Capacity (FVC) and Forced Expiratory Volume in 1 s (FEV1) are reduced without a corresponding decrement in the FEV1.FVC( - 1) %. It is not known whether this is due to the weight of the load acting on the chest or to the tightness of fit of the shoulder and chest straps and waist belt of the pack harness. This study examined FVC, FEV1, FEV1.FVC( - 1) %, peak expiratory flow (PEF), forced expiratory flow between 0.2 and 1.2 s (FEF0.2 - 1.2) after the start of expiration and between 25 and 75% of each FVC (FEF25 - 75%) in 12 healthy males wearing a 15 kg backpack in which the shoulder and chest straps and hip belt were loosened by 3 cm from a 'comfort fit' to achieve a 'loose pack' fit (LPF) and tightened by 3 cm from CF to achieve a 'tight pack' fit (TPF). In comparison with the control condition of no pack, a loose pack fit significantly reduced FVC (by 3.6%, p < 0.01), FEV1 (by 4.3%, p < 0.01) and FEF25 - 75% (by 8.4%, p < 0.01). A tight pack fit significantly reduced FVC (by 8.1%, p < 0.01) and FEV1 (by 9.1%, p < 0.001). It also significantly reduced FEF0.2 - 1.2 (by 7.3%, p < 0.05) and FEF25 - 75% (by 21%, p < 0.01). In comparison with a loose pack fit, the tight pack fit was associated with a significantly lower FVC (by 4.6%, p < 0.01), FEV1 (by 5.0%, p < 0.01), FEF25 - 75% (by 13.8%, p < 0.01) and a fall in FEF0.2 - 1.2 (by 5.5%). The latter was approaching significance (p = 0.077). There were no significant changes in FEV1.FVC( - 1)% and PEF. It is concluded that tightening the fit of a backpack significantly affects lung function in a manner that is typical of a restrictive change in lung function and is very similar in pattern to that of wearing a loosely fitted loaded backpack. The effect of tightness of fit is additional to that due to the weight of the load alone and may also reduce expiratory flow at low lung volumes. PMID

  11. Evaluation of left and right ventricular myocardial function after lung resection using speckle tracking echocardiography

    PubMed Central

    Wang, Zhenhua; Yuan, Jianjun; Chu, Wen; Kou, Yuhong; Zhang, Xijun

    2016-01-01

    Abstract The impact of major lung resections on myocardial function has not been well-investigated. We aimed to identify this impact through the use of speckle tracking echocardiography (STE) to evaluate the right and left ventricular myocardial function in patients who underwent lung resections. Thirty patients who had lung resections were recruited for this study. Ten patients who underwent pneumonectomies were matched by age and sex, with 20 patients who underwent lobectomies. STE was performed on both right and left ventricle (RV and LV). Strain values of pre and postlung resections were compared in both the pneumonectomy group and the lobectomy group. Comparison between the pneumonectomy group and the lobectomy group was also studied. Left ventricular ejection fraction remained normal (>55%), but significantly decreased after lung resection in both the pneumonectomy group and the lobectomy group. An accelerated heart rate was observed in both groups after lung resection, with the pneumonectomy group demonstrating extra rapid heart rate (P < 0.05). Strain values in the RV and LV decreased in both groups after lung resection, with the pneumonectomy group exhibiting a further decrease in longitudinal strain in LV and RV when compared with the lobectomy group (P < 0.05). Right and left ventricular dysfunction can occur after lung resection regardless of pneumonectomy or lobectomy, and lobectomy may have a less significant impact on myocardial functions. This study demonstrated that STE is able to detect acute cardiac dysfunction after lung resection. PMID:27495031

  12. Adenosine A2A Agonist Improves Lung Function During Ex-vivo Lung Perfusion

    PubMed Central

    Emaminia, Abbas; LaPar, Damien J.; Zhao, Yunge; Steidle, John F.; Harris, David A.; Linden, Joel; Kron, Irving L.; Lau, Christine L.

    2012-01-01

    Background Ex-vivo lung perfusion (EVLP) is a novel technique to assess, and potentially repair marginal lungs that may otherwise be rejected for transplantation. Adenosine has been shown to protect against lung ischemia-reperfusion injury through its A2A receptor. We hypothesized that combining EVLP with adenosine A2A receptor agonist treatment would enhance lung functional quality and increase donor lung usage. Methods Eight bilateral pig lungs were harvested and flushed with cold Perfadex. After 14 hours storage at 4°C, EVLP was performed for 5 hours on two explanted lung groups: 1) Control group lungs (n=4), were perfused with Steen Solution and Dimethyl sulfoxide (DMSO), and 2) treated group lungs (n=4) received 10μM CGS21680, a selective A2A receptor agonist, in a Steen Solution-primed circuit. Lung histology, tissue cytokines, gas analysis and pulmonary function were compared between groups. Results Treated lungs demonstrated significantly less edema as reflected by wet-dry weight ratio (6.6 vs. 5.2, p<0.03) and confirmed by histology. In addition, treated lung demonstrated significantly lower levels of interferon gamma (45.1 vs. 88.5, p<0.05). Other measured tissue cytokines (interleukin (IL) 1 beta, IL-6, and IL-8) were lower in treatment group, but values failed to reach statistical significance. Oxygenation index was improved in the treated group (1.5 vs. 2.3, p<0.01) as well as mean airway pressure (10.3 vs. 13 p<0.009). Conclusions EVLP is a novel and efficient way to assess and optimize lung function and oxygen exchange within donor lungs, and the use of adenosine A2A agonist potentiates its potential. EVLP with the concomitant administration of A2A agonist may enhance donor lung quality and could increase the donor lung pool for transplantation. PMID:22051279

  13. Lymphatic function is required prenatally for lung inflation at birth

    PubMed Central

    Jakus, Zoltán; Gleghorn, Jason P.; Enis, David R.; Sen, Aslihan; Chia, Stephanie; Liu, Xi; Rawnsley, David R.; Yang, Yiqing; Hess, Paul R.; Zou, Zhiying; Yang, Jisheng; Guttentag, Susan H.; Nelson, Celeste M.

    2014-01-01

    Mammals must inflate their lungs and breathe within minutes of birth to survive. A key regulator of neonatal lung inflation is pulmonary surfactant, a lipoprotein complex which increases lung compliance by reducing alveolar surface tension (Morgan, 1971). Whether other developmental processes also alter lung mechanics in preparation for birth is unknown. We identify prenatal lymphatic function as an unexpected requirement for neonatal lung inflation and respiration. Mice lacking lymphatic vessels, due either to loss of the lymphangiogenic factor CCBE1 or VEGFR3 function, appear cyanotic and die shortly after birth due to failure of lung inflation. Failure of lung inflation is not due to reduced surfactant levels or altered development of the lung but is associated with an elevated wet/dry ratio consistent with edema. Embryonic studies reveal active lymphatic function in the late gestation lung, and significantly reduced total lung compliance in late gestation embryos that lack lymphatics. These findings reveal that lymphatic vascular function plays a previously unrecognized mechanical role in the developing lung that prepares it for inflation at birth. They explain respiratory failure in infants with congenital pulmonary lymphangiectasia, and suggest that inadequate late gestation lymphatic function may also contribute to respiratory failure in premature infants. PMID:24733830

  14. Influencing the decline of lung function in COPD: use of pharmacotherapy.

    PubMed

    Gladysheva, Ekaterina S; Malhotra, Atul; Owens, Robert L

    2010-01-01

    Chronic obstructive pulmonary disease (COPD) is a common and deadly disease. One of the hallmarks of COPD is an accelerated decline in lung function, as measured by spirometry. Inflammation, oxidative stress and other pathways are hypothesized to be important in this deterioration. Because progressive airflow obstruction is associated with considerable morbidity and mortality, a major goal of COPD treatment has been to slow or prevent the accelerated decline in lung function. Until recently, the only known effective intervention was smoking cessation. However, newly reported large clinical trials have shown that commonly used medications may help slow the rate of lung function decline. The effect of these medications is modest (and thus required such large, expensive trials) and to be of clinical benefit, therapy would likely need to start early in the course of disease and be prolonged. Such a treatment strategy aimed at preservation of lung function would need to be balanced against the side effects and costs of prolonged therapy. A variety of newer classes of medications may help target other pathophysiologically important pathways, and could be used in the future to prevent lung function decline in COPD. PMID:20631815

  15. A prospective study of decline in lung function in relation to welding emissions

    PubMed Central

    Christensen, Sigve W; Bonde, Jens Peter; Omland, Øyvind

    2008-01-01

    Background Numerous cross-sectional studies have reported reduced lung function among welders but limitations of exposure assessment and design preclude causal inference. The aim of this study was to investigate if long-term exposure to welding fume particulates accelerates the age-related decline in lung function. Methods Lung function was measured by spirometry in 1987 and 2004 among 68 steel welders and 32 non-welding production workers. The decline in forced expiratory volume (FEV1) was analysed in relation to cumulated exposure to fume particulates among welders during the follow-up period. Results Among smokers the decline in FEV1 through follow-up period was in average 150 ml larger among welders than non-welders while the difference was negligible among non-smokers. The results did not reach statistical significance and within welders the decline in lung function was not related to the cumulated welding particulate exposure during follow-up period Conclusion Long-term exposure to welding emissions may accelerate the age-related decline of lung function but at exposure levels in the range of 1.5 to 6.5 mg/m3 the average annual excess loss of FEV1 is unlikely to exceed 25 ml in smokers and 10 ml in non-smokers. PMID:18302754

  16. 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

  17. 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

  18. Twist1 Suppresses Senescence Programs and Thereby Accelerates and Maintains Mutant Kras-Induced Lung Tumorigenesis

    PubMed Central

    Thiyagarajan, Saravanan; Das, Sandhya T.; Zabuawala, Tahera; Chen, Joy; Cho, Yoon-Jae; Luong, Richard; Tamayo, Pablo; Salih, Tarek; Aziz, Khaled; Adam, Stacey J.; Vicent, Silvestre; Nielsen, Carsten H.; Withofs, Nadia; Sweet-Cordero, Alejandro; Gambhir, Sanjiv S.; Rudin, Charles M.; Felsher, Dean W.

    2012-01-01

    KRAS mutant lung cancers are generally refractory to chemotherapy as well targeted agents. To date, the identification of drugs to therapeutically inhibit K-RAS have been unsuccessful, suggesting that other approaches are required. We demonstrate in both a novel transgenic mutant Kras lung cancer mouse model and in human lung tumors that the inhibition of Twist1 restores a senescence program inducing the loss of a neoplastic phenotype. The Twist1 gene encodes for a transcription factor that is essential during embryogenesis. Twist1 has been suggested to play an important role during tumor progression. However, there is no in vivo evidence that Twist1 plays a role in autochthonous tumorigenesis. Through two novel transgenic mouse models, we show that Twist1 cooperates with KrasG12D to markedly accelerate lung tumorigenesis by abrogating cellular senescence programs and promoting the progression from benign adenomas to adenocarcinomas. Moreover, the suppression of Twist1 to physiological levels is sufficient to cause Kras mutant lung tumors to undergo senescence and lose their neoplastic features. Finally, we analyzed more than 500 human tumors to demonstrate that TWIST1 is frequently overexpressed in primary human lung tumors. The suppression of TWIST1 in human lung cancer cells also induced cellular senescence. Hence, TWIST1 is a critical regulator of cellular senescence programs, and the suppression of TWIST1 in human tumors may be an effective example of pro-senescence therapy. PMID:22654667

  19. 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. PMID:25805449

  20. 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. PMID:27635172

  1. 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.

  2. 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

  3. The efffect of sustained +Gz acceleration on extravascular lung water content in domestic fowl.

    PubMed

    Weidner, W J; Hoffman, L F

    1980-06-01

    In order to examine the effects of sustained acceleration on pulmonary fluid balance, chickens were centrifuged at low sustained +G acceleration (LSG) intensities of +3Gz or +4Gz or high sustained +G acceleration (HSG) at +6Gz for varying periods. Animals were exposed to acceleration on a hydraulic-driven centrifuge. Controls (Group I) were not centrifuged. The vascular lungs were rapidly excised after centrifugation, and the extravascular lung water content (EVLW) was measured. EVLW in Group I animals = 2.19 +/- 0.38 g/g. Results indicate that positive acceleration elevated in animals exposed to +4Gz for 60 min (Group III). In this group, EVLW = 3.01 +/- 1.07 g/g. This increase is largely attributable to an elevated EVLW in those animals which died as a result of centrifugation, in which EVLW = 3.90 +/- 1.04 g/g. Exposure to +3Gz for 120 min (Group II) or +6Gz for periods up to 50 min (Group IV) did not produce significant elevations in EVLW in either group as a whole, but EVLW in those Group II animals which died as a result of centrifugation was significantly elevated. EVLW in these animals = 2.87 +/- 0.21 g/g. We conclude that pulmonary edema caused by centrifugation is dependent on both magnitude and duration of G force. PMID:7417119

  4. 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

  5. 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

  6. MIIP accelerates epidermal growth factor receptor protein turnover and attenuates proliferation in non-small cell lung cancer

    PubMed Central

    Wen, Jing; Fu, Jianhua; Ling, Yihong; Zhang, Wei

    2016-01-01

    The migration and invasion inhibitory protein (MIIP) has been discovered recently to have inhibitory functions in cell proliferation and migration. Overexpression of MIIP reduced the intracellular steady-state level of epidermal growth factor receptor (EGFR) protein in lung cancer cells with no effect on EGFR mRNA expression compared to that in the control cells. This MIIP-promoted EGFR protein degradation was reversed by proteasome and lysosome inhibitors, suggesting the involvement of both proteasomal and lysosomal pathways in this degradation. This finding was further validated by pulse-chase experiments using 35S-methionine metabolic labeling. We found that MIIP accelerates EGFR protein turnover via proteasomal degradation in the endoplasmic reticulum and then via the lysosomal pathway after its entry into endocytic trafficking. MIIP-stimulated downregulation of EGFR inhibits downstream activation of Ras and blocks the MEK signal transduction pathway, resulting in inhibition of cell proliferation. The negative correlation between MIIP and EGFR protein expression was validated in lung adenocarcinoma samples. Furthermore, the higher MIIP protein expression predicts a better overall survival of Stage IA-IIIA lung adenocarcinoma patients who underwent radical surgery. These findings reveal a new mechanism by which MIIP inhibits cell proliferation. PMID:26824318

  7. 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

  8. Lung function tests in neonates and infants with chronic lung disease: lung and chest-wall mechanics.

    PubMed

    Gappa, Monika; Pillow, J Jane; Allen, Julian; Mayer, Oscar; Stocks, Janet

    2006-04-01

    This is the fifth paper in a review series that summarizes available data and critically discusses the potential role of lung function testing in infants and young children with acute neonatal respiratory disorders and chronic lung disease of infancy (CLDI). This review focuses on respiratory mechanics, including chest-wall and tissue mechanics, obtained in the intensive care setting and in infants during unassisted breathing. Following orientation of the reader to the subject area, we focused comments on areas of enquiry proposed in the introductory paper to this series. The quality of the published literature is reviewed critically with respect to relevant methods, equipment and study design, limitations and strengths of different techniques, and availability and appropriateness of reference data. Recommendations to guide future investigations in this field are provided. Numerous different methods have been used to assess respiratory mechanics with the aims of describing pulmonary status in preterm infants and assessing the effect of therapeutic interventions such as surfactant treatment, antenatal or postnatal steroids, or bronchodilator treatment. Interpretation of many of these studies is limited because lung volume was not measured simultaneously. In addition, populations are not comparable, and the number of infants studied has generally been small. Nevertheless, results appear to support the pathophysiological concept that immaturity of the lung leads to impaired lung function, which may improve with growth and development, irrespective of the diagnosis of chronic lung disease. To fully understand the impact of immaturity on the developing lung, it is unlikely that a single parameter such as respiratory compliance or resistance will accurately describe underlying changes. Assessment of respiratory mechanics will have to be supplemented by assessment of lung volume and airway function. New methods such as the low-frequency forced oscillation technique, which

  9. Validating Excised Rodent Lungs for Functional Hyperpolarized Xenon-129 MRI

    PubMed Central

    Lilburn, David M. L.; Hughes-Riley, Theodore; Six, Joseph S.; Stupic, Karl F.; Shaw, Dominick E.; Pavlovskaya, Galina E.; Meersmann, Thomas

    2013-01-01

    Ex vivo rodent lung models are explored for physiological measurements of respiratory function with hyperpolarized (hp) 129Xe MRI. It is shown that excised lung models allow for simplification of the technical challenges involved and provide valuable physiological insights that are not feasible using in vivo MRI protocols. A custom designed breathing apparatus enables MR images of gas distribution on increasing ventilation volumes of actively inhaled hp 129Xe. Straightforward hp 129Xe MRI protocols provide residual lung volume (RV) data and permit for spatially resolved tracking of small hp 129Xe probe volumes during the inhalation cycle. Hp 129Xe MRI of lung function in the excised organ demonstrates the persistence of post mortem airway responsiveness to intravenous methacholine challenges. The presented methodology enables physiology of lung function in health and disease without additional regulatory approval requirements and reduces the technical and logistical challenges with hp gas MRI experiments. The post mortem lung functional data can augment histological measurements and should be of interest for drug development studies. PMID:24023683

  10. Tumor necrosis factor-α accelerates the resolution of established pulmonary fibrosis in mice by targeting profibrotic lung macrophages.

    PubMed

    Redente, Elizabeth F; Keith, Rebecca C; Janssen, William; Henson, Peter M; Ortiz, Luis A; Downey, Gregory P; Bratton, Donna L; Riches, David W H

    2014-04-01

    Idiopathic pulmonary fibrosis (IPF) is a relentless, fibrotic parenchymal lung disease in which alternatively programmed macrophages produce profibrotic molecules that promote myofibroblast survival and collagen synthesis. Effective therapies to treat patients with IPF are lacking, and conventional therapy may be harmful. We tested the hypothesis that therapeutic lung delivery of the proinflammatory cytokine tumor necrosis factor (TNF)-α into wild-type fibrotic mice would reduce the profibrotic milieu and accelerate the resolution of established pulmonary fibrosis. Fibrosis was assessed in bleomycin-instilled wild-type and TNF-α(-/-) mice by measuring hydroxyproline levels, static compliance, and Masson's trichrome staining. Macrophage infiltration and programming status was assessed by flow cytometry of enzymatically digested lung and in situ immunostaining. Pulmonary delivery of TNF-α to wild-type mice with established pulmonary fibrosis was found to reduce their fibrotic burden, to improve lung function and architecture, and to reduce the number and programming status of profibrotic alternatively programmed macrophages. In contrast, fibrosis and alternative macrophage programming were prolonged in bleomycin-instilled TNF-α(-/-) mice. To address the role of the reduced numbers of alternatively programmed macrophages in the TNF-α-induced resolution of established pulmonary fibrosis, we conditionally depleted macrophages in MAFIA (MAcrophage Fas-Induced Apoptosis) mice. Conditional macrophage depletion phenocopied the resolution of established pulmonary fibrosis observed after therapeutic TNF-α delivery. Taken together, our results show for the first time that TNF-α is involved in the resolution of established pulmonary fibrosis via a mechanism involving reduced numbers and programming status of profibrotic macrophages. We speculate that pulmonary delivery of TNF-α or augmenting its signaling pathway represent a novel therapeutic strategy to resolve

  11. 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.

  12. Transfer function between tibial acceleration and ground reaction force.

    PubMed

    Lafortune, M A; Lake, M J; Hennig, E

    1995-01-01

    The purpose of the present study was to capture the relationship between ground reaction force (GRF) and tibial axial acceleration. Tibia acceleration and GRF were simultaneously recorded from five subjects during running. The acceleration of the bone was measured with a transducer mounted onto an intracortical pin. The signals were analyzed in the frequency domain to characterize the relationship between GRF and tibial acceleration. The results confirmed that for each subject this relationship could be represented by a frequency transfer function. The existence of a more general relationship for all five subjects was also confirmed by the results. The transfer functions provided information about transient shock transmissibility for the entire impact phase of running.

  13. Functional Error Models to Accelerate Nested Sampling

    NASA Astrophysics Data System (ADS)

    Josset, L.; Elsheikh, A. H.; Demyanov, V.; Lunati, I.

    2014-12-01

    The main challenge in groundwater problems is the reliance on large numbers of unknown parameters with wide rage of associated uncertainties. To translate this uncertainty to quantities of interest (for instance the concentration of pollutant in a drinking well), a large number of forward flow simulations is required. To make the problem computationally tractable, Josset et al. (2013, 2014) introduced the concept of functional error models. It consists in two elements: a proxy model that is cheaper to evaluate than the full physics flow solver and an error model to account for the missing physics. The coupling of the proxy model and the error models provides reliable predictions that approximate the full physics model's responses. The error model is tailored to the problem at hand by building it for the question of interest. It follows a typical approach in machine learning where both the full physics and proxy models are evaluated for a training set (subset of realizations) and the set of responses is used to construct the error model using functional data analysis. Once the error model is devised, a prediction of the full physics response for a new geostatistical realization can be obtained by computing the proxy response and applying the error model. We propose the use of functional error models in a Bayesian inference context by combining it to the Nested Sampling (Skilling 2006; El Sheikh et al. 2013, 2014). Nested Sampling offers a mean to compute the Bayesian Evidence by transforming the multidimensional integral into a 1D integral. The algorithm is simple: starting with an active set of samples, at each iteration, the sample with the lowest likelihood is kept aside and replaced by a sample of higher likelihood. The main challenge is to find this sample of higher likelihood. We suggest a new approach: first the active set is sampled, both proxy and full physics models are run and the functional error model is build. Then, at each iteration of the Nested

  14. 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

  15. 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

  16. The optical properties of lung as a function of respiration

    NASA Astrophysics Data System (ADS)

    Beek, J. F.; van Staveren, H. J.; Posthumus, P.; Sterenborg, H. J. C. M.; van Gemert, M. J. C.

    1997-11-01

    Lung consists of alveoli enclosed by tissue and both structures contribute to volume-dependent scattering of light. It is the purpose of this paper to determine the volume-dependent optical properties of lung. In vivo interstitial fibre measurements of the effective attenuation coefficient at 632.8 nm differed during inspiration from that during expiration . In vitro measurements on a piglet lung insufflated with oxygen from 50 to 150 ml showed the effective attenuation coefficient at 632.8 nm decreases as a function of oxygen volume in the lung (at 50 ml , at 100 ml , and at 150 ml ). This was explained by combining scattering of alveoli (Mie theory) with optical properties of collapsed lung tissue using integrating sphere measurements. Theory and measured in vitro values showed good agreement (deviation ). Combination of these data yields the absorption coefficient and scattering parameters of lung tissue as a function of lung volume. We conclude that the light fluence rate in lung tissue should be estimated using optical properties that include scattering by the alveoli.

  17. 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.

  18. 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. PMID:26395457

  19. 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.

  20. [INFLUENCE OF LIPOSUCTION OF LARGE VOLUME ON SYSTEMIC AND LUNG CIRCULATION, OXIGENATED LUNG FUNCTION].

    PubMed

    Nikolaeva, I P; Kapranova, A S; Popova, V B; Lodyagin, A N; Frolova, T A

    2015-01-01

    The authors measured the changes of hemodynamics in 72 patients. It was also estimated a blood oxygenation and volume of liquid sectors of the organism in different degree of obesity before and after liposuction of the large volume. It was shown, that this operation facilitated to an improvement of respiratory lung function due to changes of pulmonary circulation.

  1. 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...

  2. 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.

  3. Source Time Function of P-wave Acceleration

    NASA Astrophysics Data System (ADS)

    Chen, K. J.

    2015-12-01

    In this study, the site effect of time function of the Taiwan area will be invested. The recorded response function of a single earthquake will be calculated by Complex Demodulation. The path effect of each event-station pair will be estimated by using the forward method with a 3-D attenuation structure. After removing the path effect, the source frequency function of each single event will be obtained by averaging the whole station gotten. Using this source time function to calculate the path effect of the all stations, the theoretic received time frequency function can be obtained. The difference between this theoretic function and the recorded function is the site effect function of the single station. The characterics of the site effect in Taiwan area will be analyzed. Recalculate the path effect and remove the site effect of each station to get the new source time function of P-wave acceleration.

  4. Leg joint function during walking acceleration and deceleration.

    PubMed

    Qiao, Mu; Jindrich, Devin L

    2016-01-01

    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.

  5. Acceleration of reverse analysis method using hyperbolic activation function

    NASA Astrophysics Data System (ADS)

    Pwasong, Augustine; Sathasivam, Saratha

    2015-10-01

    Hyperbolic activation function is examined for its ability to accelerate the performance of doing data mining by using a technique named as Reverse Analysis method. In this paper, we describe how Hopfield network perform better with hyperbolic activation function and able to induce logical rules from large database by using reverse analysis method: given the values of the connections of a network, we can hope to know what logical rules are entrenched in the database. We limit our analysis to Horn clauses.

  6. Lung Endoderm Morphogenesis: Gasping for Form and Function

    PubMed Central

    Swarr, Daniel T.; Morrisey, Edward E.

    2016-01-01

    The respiratory endoderm develops from a small cluster of cells located on the ventral anterior foregut. This population of progenitors generates the myriad epithelial lineages required for proper lung function in adults through a complex and delicately balanced series of developmental events controlled by many critical signaling and transcription factor pathways. In the past decade, understanding of this process has grown enormously, helped in part by cell lineage fate analysis and deep sequencing of the transcriptomes of various progenitors and differentiated cell types. This review explores how these new techniques, coupled with more traditional approaches, have provided a detailed picture of development of the epithelial lineages in the lung and insight into how aberrant development can lead to lung disease. PMID:26359777

  7. Lung function and ventilation inhomogeneity in rat lungs after allergen challenge.

    PubMed

    Sánchez-Cifuentes, M V; Rubio, M L; Ortega, M; Peces-Barba, G; Paiva, M; Verbanck, S; Mangado, N G

    2000-03-01

    We studied the early response to ovalbumin challenge in sensitized Brown-Norway rats through its effect on N(2), He, and SF(6) phase III slopes of the single-breath washout and on indexes of lung function. Sensitized rats showed varying degrees of response in terms of pulmonary pressure (PL), with increases ranging between 125 and 225% of baseline. The sensitized rats presented decreased quasistatic compliance, forced vital capacity, and end-expiratory flow, with all three lung function indexes showing a significant negative correlation with corresponding PL values. They also showed significant positive correlations of PL with the N(2), He, and SF(6) phase III slopes, reflecting diffusion-convection-dependent inhomogeneities generated by conformation changes throughout the entire rat lung. In addition, the rats showing the most marked PL increases (>150% baseline PL) also revealed a reversal of the SF(6)-He slope difference because of a more marked SF(6) than He slope increase. This latter finding suggests that the degree of structural heterogeneity during early response is even more marked in the most peripheral rat lung generations.

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

    PubMed

    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.

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

    PubMed

    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. PMID:26048584

  10. 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

  11. 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

  12. 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.

  13. 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.

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

    PubMed

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

    2013-09-01

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

  15. Pyrosequencing Unveils Cystic Fibrosis Lung Microbiome Differences Associated with a Severe Lung Function Decline.

    PubMed

    Bacci, Giovanni; Paganin, Patrizia; Lopez, Loredana; Vanni, Chiara; Dalmastri, Claudia; Cantale, Cristina; Daddiego, Loretta; Perrotta, Gaetano; Dolce, Daniela; Morelli, Patrizia; Tuccio, Vanessa; De Alessandri, Alessandra; Fiscarelli, Ersilia Vita; Taccetti, Giovanni; Lucidi, Vincenzina; Bevivino, Annamaria; Mengoni, Alessio

    2016-01-01

    Chronic airway infection is a hallmark feature of cystic fibrosis (CF) disease. In the present study, sputum samples from CF patients were collected and characterized by 16S rRNA gene-targeted approach, to assess how lung microbiota composition changes following a severe decline in lung function. In particular, we compared the airway microbiota of two groups of patients with CF, i.e. patients with a substantial decline in their lung function (SD) and patients with a stable lung function (S). The two groups showed a different bacterial composition, with SD patients reporting a more heterogeneous community than the S ones. Pseudomonas was the dominant genus in both S and SD patients followed by Staphylococcus and Prevotella. Other than the classical CF pathogens and the most commonly identified non-classical genera in CF, we found the presence of the unusual anaerobic genus Sneathia. Moreover, the oligotyping analysis revealed the presence of other minor genera described in CF, highlighting the polymicrobial nature of CF infection. Finally, the analysis of correlation and anti-correlation networks showed the presence of antagonism and ecological independence between members of Pseudomonas genus and the rest of CF airways microbiota, with S patients showing a more interconnected community in S patients than in SD ones. This population structure suggests a higher resilience of S microbiota with respect to SD, which in turn may hinder the potential adverse impact of aggressive pathogens (e.g. Pseudomonas). In conclusion, our findings shed a new light on CF airway microbiota ecology, improving current knowledge about its composition and polymicrobial interactions in patients with CF. PMID:27355625

  16. 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

  17. Pyrosequencing Unveils Cystic Fibrosis Lung Microbiome Differences Associated with a Severe Lung Function Decline

    PubMed Central

    Bacci, Giovanni; Paganin, Patrizia; Lopez, Loredana; Vanni, Chiara; Dalmastri, Claudia; Cantale, Cristina; Daddiego, Loretta; Perrotta, Gaetano; Dolce, Daniela; Morelli, Patrizia; Tuccio, Vanessa; De Alessandri, Alessandra; Fiscarelli, Ersilia Vita; Taccetti, Giovanni; Lucidi, Vincenzina; Mengoni, Alessio

    2016-01-01

    Chronic airway infection is a hallmark feature of cystic fibrosis (CF) disease. In the present study, sputum samples from CF patients were collected and characterized by 16S rRNA gene-targeted approach, to assess how lung microbiota composition changes following a severe decline in lung function. In particular, we compared the airway microbiota of two groups of patients with CF, i.e. patients with a substantial decline in their lung function (SD) and patients with a stable lung function (S). The two groups showed a different bacterial composition, with SD patients reporting a more heterogeneous community than the S ones. Pseudomonas was the dominant genus in both S and SD patients followed by Staphylococcus and Prevotella. Other than the classical CF pathogens and the most commonly identified non-classical genera in CF, we found the presence of the unusual anaerobic genus Sneathia. Moreover, the oligotyping analysis revealed the presence of other minor genera described in CF, highlighting the polymicrobial nature of CF infection. Finally, the analysis of correlation and anti-correlation networks showed the presence of antagonism and ecological independence between members of Pseudomonas genus and the rest of CF airways microbiota, with S patients showing a more interconnected community in S patients than in SD ones. This population structure suggests a higher resilience of S microbiota with respect to SD, which in turn may hinder the potential adverse impact of aggressive pathogens (e.g. Pseudomonas). In conclusion, our findings shed a new light on CF airway microbiota ecology, improving current knowledge about its composition and polymicrobial interactions in patients with CF. PMID:27355625

  18. 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.

  19. 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.

  20. Genetic Ancestry Influences Asthma Susceptibility and Lung Function Among Latinos

    PubMed Central

    Pino-Yanes, Maria; Thakur, Neeta; Gignoux, Christopher R.; Galanter, Joshua M.; Roth, Lindsey A.; Eng, Celeste; Nishimura, Katherine K.; Oh, Sam S.; Vora, Hita; Huntsman, Scott; Nguyen, Elizabeth A.; Hu, Donglei; Drake, Katherine A.; Conti, David V.; Moreno-Estrada, Andres; Sandoval, Karla; Winkler, Cheryl A.; Borrell, Luisa N.; Lurmann, Fred; Islam, Talat S.; Davis, Adam; Farber, Harold J.; Meade, Kelley; Avila, Pedro C.; Serebrisky, Denise; Bibbins-Domingo, Kirsten; Lenoir, Michael A.; Ford, Jean G.; Brigino-Buenaventura, Emerita; Rodriguez-Cintron, William; Thyne, Shannon M.; Sen, Saunak; Rodriguez-Santana, Jose R.; Bustamante, Carlos D.; Williams, L. Keoki; Gilliland, Frank D.; Gauderman, W. James; Kumar, Rajesh; Torgerson, Dara G.; Burchard, Esteban G.

    2014-01-01

    Background Childhood asthma prevalence and morbidity varies among Latinos in the United States, with Puerto Ricans having the highest and Mexicans the lowest. Objective To determine whether genetic ancestry is associated with the odds of asthma among Latinos, and secondarily whether genetic ancestry is associated with lung function among Latino children. Methods We analyzed 5,493 Latinos with and without asthma from three independent studies. For each participant we estimated the proportion of African, European, and Native American ancestry using genome-wide data. We tested whether genetic ancestry was associated with the presence of asthma and lung function among subjects with and without asthma. Odds ratios (OR) and effect sizes were assessed for every 20% increase in each ancestry. Results Native American ancestry was associated with lower odds of asthma (OR=0.72, 95% confidence interval [CI]: 0.66–0.78, p=8.0×10−15), while African ancestry was associated with higher odds of asthma (OR=1.40, 95%CI: 1.14–1.72, p=0.001). These associations were robust to adjustment for covariates related to early life exposures, air pollution and socioeconomic status. Among children with asthma, African ancestry was associated with lower lung function, including both pre- and post-bronchodilator measures of forced expiratory volume in the first second (−77±19 ml, p=5.8×10−5 and −83±19 ml, p=1.1×10−5, respectively) and forced vital capacity (−100±21 ml, p=2.7×10−6 and −107±22 ml, p=1.0×10−6, respectively). Conclusion Differences in the proportions of genetic ancestry can partially explain disparities in asthma susceptibility and lung function among Latinos. PMID:25301036

  1. African ancestry, lung function and the effect of genetics

    PubMed Central

    Wehrmeister, Fernando C.; Hartwig, Fernando P.; Perez-Padilla, Rogelio; Gigante, Denise P.; Barros, Fernando C.; Oliveira, Isabel O.; Ferreira, Gustavo D.; Horta, Bernardo L.

    2015-01-01

    African-Americans have smaller lung function compared with European-Americans. The aim of this study was to disentangle the contribution of genetics from other variables on lung function. A cohort was followed from birth to 30 years of age in Brazil. Several variables were collected: genomic analysis based on DNA; forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) obtained by spirometry; height measured by anthropometrists; and thorax circumference evaluated by photonic scanner. Crude and adjusted linear regression models were calculated according to African ancestry. The sample comprised 2869 participants out of 3701 members of the cohort. Males with higher African ancestry by DNA analysis had a smaller FEV1 (−0.13 L, 95% CI −0.23– −0.03 L) and FVC (−0.21 L, 95% CI −0.32– −0.09 L) compared with those with less African ancestry, having accounted for height, sitting to standing height ratio and other confounders. Similar effects were seen in females. After adjustment, ancestry remained significantly associated with lung function, but the large effect of adjustment for confounding among males (but not females) does not allow us to exclude the possibility that residual confounding may still account for these findings. PMID:25700383

  2. Influence of Pulmonary Rehabilitation on Lung Function Changes After the Lung Resection for Primary Lung Cancer in Patients with Chronic Obstructive Pulmonary Disease.

    PubMed

    Mujovic, Natasa; Mujovic, Nebojsa; Subotic, Dragan; Ercegovac, Maja; Milovanovic, Andjela; Nikcevic, Ljubica; Zugic, Vladimir; Nikolic, Dejan

    2015-11-01

    Influence of physiotherapy on the outcome of the lung resection is still controversial. Study aim was to assess the influence of physiotherapy program on postoperative lung function and effort tolerance in lung cancer patients with chronic obstructive pulmonary disease (COPD) that are undergoing lobectomy or pneumonectomy. The prospective study included 56 COPD patients who underwent lung resection for primary non small-cell lung cancer after previous physiotherapy (Group A) and 47 COPD patients (Group B) without physiotherapy before lung cancer surgery. In Group A, lung function and effort tolerance on admission were compared with the same parameters after preoperative physiotherapy. Both groups were compared in relation to lung function, effort tolerance and symptoms change after resection. In patients with tumors requiring a lobectomy, after preoperative physiotherapy, a highly significant increase in FEV1, VC, FEF50 and FEF25 of 20%, 17%, 18% and 16% respectively was registered with respect to baseline values. After physiotherapy, a significant improvement in 6-minute walking distance was achieved. After lung resection, the significant loss of FEV1 and VC occurred, together with significant worsening of the small airways function, effort tolerance and symptomatic status. After the surgery, a clear tendency existed towards smaller FEV1 loss in patients with moderate to severe, when compared to patients with mild baseline lung function impairment. A better FEV1 improvement was associated with more significant loss in FEV1. Physiotherapy represents an important part of preoperative and postoperative treatment in COPD patients undergoing a lung resection for primary lung cancer. PMID:26618048

  3. 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.

  4. 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

  5. Improved Air Quality and Attenuated Lung Function Decline: Modification by Obesity in the SAPALDIA Cohort

    PubMed Central

    Schaffner, Emmanuel; Meier, Flurina; Phuleria, Harish C.; Vierkötter, Andrea; Schindler, Christian; Kriemler, Susi; Zemp, Elisabeth; Krämer, Ursula; Bridevaux, Pierre-Olivier; Rochat, Thierry; Schwartz, Joel; Künzli, Nino; Probst-Hensch, Nicole

    2013-01-01

    Background: Air pollution and obesity are hypothesized to contribute to accelerated decline in lung function with age through their inflammatory properties. Objective: We investigated whether the previously reported association between improved air quality and lung health in the population-based SAPALDIA cohort is modified by obesity. Methods: We used adjusted mixed-model analyses to estimate the association of average body mass index (BMI) and changes in particulate matter with aerodynamic diameter ≤ 10 µm (PM10; ΔPM10) with lung function decline over a 10-year follow-up period. Results: Lung function data and complete information were available for 4,664 participants. Age-related declines in lung function among participants with high average BMI were more rapid for FVC (forced vital capacity), but slower for FEV1/FVC (forced expiratory volume in 1 sec/FVC) and FEF25–75 (forced expiratory flow at 25–75%) than declines among those with low or normal average BMI. Improved air quality was associated with attenuated reductions in FEV1/FVC, FEF25–75, and FEF25–75/FVC over time among low- and normal-BMI participants, but not overweight or obese participants. The attenuation was most pronounced for ΔFEF25–75/FVC (30% and 22% attenuation in association with a 10-μg/m3 decrease in PM10 among low- and normal-weight participants, respectively.) Conclusion: Our results point to the importance of considering health effects of air pollution exposure and obesity in parallel. Further research must address the mechanisms underlying the observed interaction. Citation: Schikowski T, Schaffner E, Meier F, Phuleria HC, Vierkötter A, Schindler C, Kriemler S, Zemp E, Krämer U, Bridevaux P-O, Rochat T, Schwartz J, Künzli N, Probst-Hensch N. 2013. Improved air quality and attenuated lung function decline: modification by obesity in the SAPALDIA cohort. Environ Health Perspect 121:1034–1039; http://dx.doi.org/10.1289/ehp.1206145 PMID:23820868

  6. 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.

  7. 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

  8. Small changes in lung function in runners with marathon‐induced interstitial lung edema

    PubMed Central

    Zavorsky, Gerald S.; Milne, Eric N.C.; Lavorini, Federico; Rienzi, Joseph P.; Cutrufello, Paul T.; Kumar, Sridhar S.; Pistolesi, Massimo

    2014-01-01

    Abstract The purpose of this study was to assess lung function in runners with marathon‐induced lung edema. Thirty‐six (24 males) healthy subjects, 34 (SD 9) years old, body mass index 23.7 (2.6) kg/m2 had posterior/anterior (PA) radiographs taken 1 day before and 21 (6) minutes post marathon finish. Pulmonary function was performed 1–3 weeks before and 73 (27) minutes post finish. The PA radiographs were viewed together, as a set, and evaluated by two experienced readers separately who were blinded as to time the images were obtained. Radiographs were scored for edema based on four different radiological characteristics such that the summed scores for any runner could range from 0 (no edema) to a maximum of 8 (severe interstitial edema). Overall, the mean edema score increased significantly from 0.2 to 1.0 units (P <0.01), and from 0.0 to 2.9 units post exercise in the six subjects that were edema positive (P = 0.03). Despite a 2% decrease in forced vital capacity (FVC, P =0.024) and a 12% decrease in alveolar‐membrane diffusing capacity for carbon monoxide (DmCO, P =0.01), there was no relation between the change in the edema score and the change in DmCO or FVC. In conclusion, (1) mild pulmonary edema occurs in at least 17% of subjects and that changes in pulmonary function cannot predict the occurrence or severity of edema, (2) lung edema is of minimal physiological significance as marathon performance is unaffected, exercise‐induced arterial hypoxemia is unlikely, and postexercise pulmonary function changes are mild. PMID:24973330

  9. Lung function tests in clinical decision-making.

    PubMed

    Puente Maestú, Luis; García de Pedro, Julia

    2012-05-01

    In this article, we review the utility of the most common lung function tests (spirometry, reversibility test, peak expiratory flow, lung volumes, maximal respiratory pressure, carbon monoxide transference, arterial blood gas, 6-minute walk test and desaturation with exercise and ergospirometry) related to the most frequent pathologies (dyspnea of undetermined origin, chronic cough, asthma, COPD, neuromuscular diseases, interstitial diseases, pulmonary vascular diseases, pre-operative evaluation and disability evaluation). Our analysis has been developed from the perspective of decision-making, clinical interpretation or aspects that the physician should take into account with their use. Consequently, the paper does not deal with aspects of quality, technique or equipment, with the exception of when regarding costs as we believe that this is an important element in the decision-making process. The document is extensively supported by references from the literature.

  10. Circulating MicroRNAs: Association with Lung Function in Asthma

    PubMed Central

    Kho, Alvin T.; Sharma, Sunita; Davis, Joshua S.; Spina, Joseph; Howard, Dagnie; McEnroy, Kevin; Moore, Kip; Sylvia, Jody; Qiu, Weiliang; Weiss, Scott T.; Tantisira, Kelan G.

    2016-01-01

    Background MicroRNAs are key transcriptional and network regulators previously associated with asthma susceptibility. However, their role in relation to asthma severity has not been delineated. Objective We hypothesized that circulating microRNAs could serve as biomarkers of changes in lung function in asthma patients. Methods We isolated microRNAs from serum samples obtained at randomization for 160 participants of the Childhood Asthma Management Program. Using a TaqMan microRNA array containing 754 microRNA primers, we tested for the presence of known asthma microRNAs, and assessed the association of the individual microRNAs with lung function as measured by FEV1/FVC, FEV1% and FVC%. We further tested the subset of FEV1/FVC microRNAs for sex-specific and lung developmental associations. Results Of the 108 well-detected circulating microRNAs, 74 (68.5%) had previously been linked to asthma susceptibility. We found 22 (20.3%), 4 (3.7%) and 8 (7.4%) microRNAs to be associated with FEV1/FVC, FEV1% and FVC%, respectively. 8 (of 22) FEV1/FVC, 3 (of 4) FEV1% and 1 (of 8) FVC% microRNAs had functionally validated target genes that have been linked via genome wide association studies to asthma and FEV1 change. Among the 22 FEV1/FVC microRNAs, 9 (40.9%) remain associated with FEV1/FVC in boys alone in a sex-stratified analysis (compared with 3 FEV1/FVC microRNAs in girls alone), 7 (31.8%) were associated with fetal lung development, and 3 (13.6%) in both. Ontology analyses revealed enrichment for pathways integral to asthma, including PPAR signaling, G-protein coupled signaling, actin and myosin binding, and respiratory system development. Conclusions Circulating microRNAs reflect asthma biology and are associated with lung function differences in asthmatics. They may represent biomarkers of asthma severity. PMID:27362794

  11. Undifferentiated connective tissue disease-associated interstitial lung disease: changes in lung function.

    PubMed

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

    2010-04-01

    Undifferentiated connective tissue disease (UCTD) is a distinct clinical entity that may be accompanied by interstitial lung disease (ILD). The natural history of UCTD-ILD is unknown. We hypothesized that patients with UCTD-ILD would be more likely to have improvement in lung function than those with idiopathic pulmonary fibrosis (IPF) during longitudinal follow-up. We identified subjects enrolled in the UCSF ILD cohort study with a diagnosis of IPF or UCTD. The primary outcome compared the presence or absence of a > or = 5% increase in percent predicted forced vital capacity (FVC) in IPF and UCTD. Regression models were used to account for potential confounding variables. Ninety subjects were identified; 59 subjects (30 IPF, 29 UCTD) had longitudinal pulmonary function data for inclusion in the analysis. After accounting for baseline pulmonary function tests, treatment, and duration between studies, UCTD was associated with substantial improvement in FVC (odds ratio = 8.23, 95% confidence interval, 1.27-53.2; p = 0.03) during follow-up (median, 8 months) compared with IPF. Patients with UCTD-ILD are more likely to have improved pulmonary function during follow-up than those with IPF. These findings demonstrate the clinical importance of identifying UCTD in patients presenting with an "idiopathic" interstitial pneumonia.

  12. Prospective prediction of post-radiation therapy lung function using quantitative lung scans and pulmonary function testing

    SciTech Connect

    Rubenstein, J.H.; Richter, M.P.; Moldofsky, P.J.; Solin, L.J.

    1988-07-01

    Surgeons have made use of quantitative perfusion lung scanning (QS) and forced expiratory volume in one second (FEV1) to predict a patient's ability to tolerate lung resection. In this study QS and FEV1 were used to predict prospectively pulmonary function following lung irradiation (XRT). Twenty-two patients have had QS and FEV1 determined before XRT and at planned intervals post-XRT. Serial determination of lung function post-XRT allows comment on the temporal nature of the XRT effect on lung function. Seventeen patients had QS and FEV1 determined at an interval of 2-6 months post-irradiation with a drop in the groups mean FEV1 from 1.91 to 1.87L. or 2% during that interval. In the interval from 6-12 months post-XRT, 13 patients had studies with the groups mean FEV1 dropping from 1.79 to 1.58L or 12% of the original. In the interval from 12-18 months, 6 patients had a decline in mean FEV1 from 1.73 to 1.56L. or 10% of the original. In 22 patients a predicted final FEV1 was compared with a measured value at an interval from XRT. Fourteen of these determinations were at intervals greater than 6 months from the start of XRT and 6 at intervals of greater than 1 year. FEV1 was seen to drop during the follow-up intervals toward the predicted value. In only 2 patients did the final FEV1 drop below the predicted FEV1 and never by more than 0.12L. (6%). In summary, a method for predicting post-XRT pulmonary function using QS and FEV1 is described. Serial follow-up revealed a latent period followed by a late phase where FEV1 fell toward, but not significantly below, the predicted value. Such a determination can be of value in formulating a treatment plan for patients with significantly diminished pulmonary function.

  13. 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

    2014-10-01

    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.

  14. Pulmonary function and exercise capacity after lung resection.

    PubMed

    Bolliger, C T; Jordan, P; Solèr, M; Stulz, P; Tamm, M; Wyser, C; Gonon, M; Perruchoud, A P

    1996-03-01

    The influence of pulmonary resection on functional capacity can be assessed in different ways. The aim of this study was to compare the effect of lobectomy and pneumonectomy on pulmonary function tests (PFT), exercise capacity and perception of symptoms. Sixty eight patients underwent functional assessment with PFT and exercise testing before (Preop), and 3 and 6 months after lung resection. In 50 (36 males and 14 females; mean age 61 yrs) a lobectomy was performed and in 18 (13 males and 5 females; mean age 59 yrs) a pneumonectomy was performed. Three months after lobectomy, forced vital capacity (FVC), forced expiratory volume in one second (FEV1), total lung capacity (TLC), transfer factor of the lungs for carbon monoxide (TL,CO) and maximal oxygen uptake (V'O2,max) were significantly lower than Preop values, increasing significantly from 3 to 6 months after resection. Three months after pneumonectomy, all parameters were significantly lower than Preop values and significantly lower than postlobectomy values and did not recover from 3 to 6 months after resection. At 6 months after resection significant deficits persisted in comparison with Preop: for FVC 7% and 36%, FEV1 9% and 34%, TLC 10% and 33% for lobectomy and pneumonectomy, respectively; and V'O2,max 20% after pneumonectomy only. Exercise was limited by leg muscle fatigue in 53% of all patients at Preop. This was not altered by lobectomy, but there was a switch to dyspnoea as the limiting factor after pneumonectomy (61% of patients at 3 months and 50% at 6 months after resection). Furthermore, pneumonectomy compared to lobectomy led to a significantly smaller breathing reserve (mean +/- SD) (28 +/- 13 vs 37 +/- 16% at 3 months; and 24 +/- 11% vs 33 +/- 12% at 6 months post resection) and lower arterial oxygen tension at peak exercise 10.1 +/- 1.5 vs 11.5 +/- 1.6 kPa (76 +/- 11 vs 86 +/- 12 mmHg) at 3 months; 10.1 +/- 1.3 vs 11.3 +/- 1.6 kPa (76 +/- 10 vs 85 +/- 12 mmHg) at 6 months postresection. We

  15. 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

  16. Lung Master Protocol (Lung-MAP)—A Biomarker-Driven Protocol for Accelerating Development of Therapies for Squamous Cell Lung Cancer: SWOG S1400

    PubMed Central

    Herbst, Roy S.; Gandara, David R.; Hirsch, Fred R.; Redman, Mary W.; LeBlanc, Michael; Mack, Philip C.; Schwartz, Lawrence H.; Vokes, Everett; Ramalingam, Suresh S.; Bradley, Jeffrey D.; Sparks, Dana; Zhou, Yang; Miwa, Crystal; Miller, Vincent A.; Yelensky, Roman; Li, Yali; Allen, Jeff D.; Sigal, Ellen V.; Wholley, David; Sigman, Caroline C.; Blumenthal, Gideon M.; Malik, Shakun; Kelloff, Gary J.; Abrams, Jeffrey S.; Blanke, Charles D.; Papadimitrakopoulou, Vassiliki A.

    2015-01-01

    The Lung Master Protocol (Lung-MAP, S1400) is a groundbreaking clinical trial designed to advance the efficient development of targeted therapies for squamous cell cancer (SCCA) of the lung. There are no approved targeted therapies specific to advanced lung SCCA, although The Cancer Genome Atlas (TCGA) project and similar studies have detected a significant number of somatic gene mutations/amplifications in lung SCCA, some of which are targetable by investigational agents. However, the frequency of these changes is low (5–20%), making recruitment and study conduct challenging in the traditional clinical trial setting. Here we describe our approach to development of a biomarker-driven phase 2/3 multi-substudy “Master Protocol,” employing a common platform (Next Generation DNA Sequencing) to identify actionable molecular abnormalities, followed by randomization to the relevant targeted therapy versus standard of care. PMID:25680375

  17. Lung Master Protocol (Lung-MAP)-A Biomarker-Driven Protocol for Accelerating Development of Therapies for Squamous Cell Lung Cancer: SWOG S1400.

    PubMed

    Herbst, Roy S; Gandara, David R; Hirsch, Fred R; Redman, Mary W; LeBlanc, Michael; Mack, Philip C; Schwartz, Lawrence H; Vokes, Everett; Ramalingam, Suresh S; Bradley, Jeffrey D; Sparks, Dana; Zhou, Yang; Miwa, Crystal; Miller, Vincent A; Yelensky, Roman; Li, Yali; Allen, Jeff D; Sigal, Ellen V; Wholley, David; Sigman, Caroline C; Blumenthal, Gideon M; Malik, Shakun; Kelloff, Gary J; Abrams, Jeffrey S; Blanke, Charles D; Papadimitrakopoulou, Vassiliki A

    2015-04-01

    The Lung Master Protocol (Lung-MAP, S1400) is a groundbreaking clinical trial designed to advance the efficient development of targeted therapies for squamous cell carcinoma (SCC) of the lung. There are no approved targeted therapies specific to advanced lung SCC, although The Cancer Genome Atlas project and similar studies have detected a significant number of somatic gene mutations/amplifications in lung SCC, some of which are targetable by investigational agents. However, the frequency of these changes is low (5%-20%), making recruitment and study conduct challenging in the traditional clinical trial setting. Here, we describe our approach to development of a biomarker-driven phase II/II multisubstudy "Master Protocol," using a common platform (next-generation DNA sequencing) to identify actionable molecular abnormalities, followed by randomization to the relevant targeted therapy versus standard of care.

  18. Genetic variation in antioxidant enzymes, cigarette smoking, and longitudinal change in lung function.

    PubMed

    Tang, Wenbo; Bentley, Amy R; Kritchevsky, Stephen B; Harris, Tamara B; Newman, Anne B; Bauer, Douglas C; Meibohm, Bernd; Cassano, Patricia A

    2013-10-01

    Antioxidant enzymes play an important role in the defense against oxidative stress in the lung and in the pathogenesis of chronic obstructive pulmonary disease (COPD). Sequence variation in genes encoding antioxidant enzymes may alter susceptibility to COPD by affecting longitudinal change in lung function in adults. We genotyped 384 sequence variants in 56 candidate genes in 1281 African American and 1794 European American elderly adults in the Health, Aging, and Body Composition study. Single-marker associations and gene-by-smoking interactions with rate of change in FEV₁ and FEV₁/FVC were evaluated using linear mixed-effects models, stratified by race/ethnicity. In European Americans, rs17883901 in GCLC was statistically significantly associated with rate of change in FEV₁/FVC; the recessive genotype (TT) was associated with a 0.9% per year steeper decline (P = 4.50 × 10(-5)). Statistically significant gene-by-smoking interactions were observed for variants in two genes in European Americans: the minor allele of rs2297765 in mGST3 attenuated the accelerated decline in FEV₁/FVC in smokers by 0.45% per year (P = 1.13 × 10(-4)); for participants with greater baseline smoking pack-years, the minor allele of rs2073192 in IDH3B was associated with an accelerated decline in FEV₁/FVC (P = 2.10 × 10(-4)). For both genes, nominally significant interactions (P < 0.01) were observed at the gene level in African Americans (P = 0.007 and 4.60 × 10(-4), respectively). Nominally significant evidence of association was observed for variants in SOD3 and GLRX2 in multiple analyses. This study identifies two novel genes associated with longitudinal lung function phenotypes in both African and European Americans and confirms a prior finding for GCLC. These findings suggest novel mechanisms and molecular targets for future research and advance the understanding of genetic determinants of lung function and COPD risk.

  19. 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

  20. The Association Between Urinary Phthalates and Lung Function

    PubMed Central

    Cakmak, Sabit; Hebbern, Chris; Saravanabhavan, Gurusankar

    2014-01-01

    Objective: To investigate the influence of phthalate exposure on lung function in the Canadian population. Methods: We tested the association between 1-second forced expiratory volume (FEVl), forced vital capacity (FVC), and urinary phthalate metabolite levels in a nationally representative sample of 3147, from 6 to 49 years old. Results: An interquartile increase in mono-n-butyl phthalate was associated with decreases in percent predicted FEV1 of 0.8% (95% confidence interval = 0.3 to 1.4) and in FVC of 0.9% (95% confidence interval = 0.3 to 1.5). Results were similar for mono-3-carboxypropyl phthalate, mono-benzyl phthalate, and di(2-ethylhexyl) phthalate metabolites, but significant effects of the latter were only seen in males and those at least 17 years old. Conclusions: These results provide evidence that phthalate exposure may adversely affect lung function in the Canadian population. Given that these chemicals are ubiquitous, the population health burden may be significant if the associations were causal. PMID:24709763

  1. Anti-muscarinic adjunct therapy accelerates functional human oligodendrocyte repair.

    PubMed

    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; Sim, Fraser J

    2015-02-25

    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.

  2. 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

  3. 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

    2016-04-01

    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.

  4. Relationship of lung function to radiographic reading (ILO) in patients with asbestos related lung disease.

    PubMed

    Cotes, J E; King, B

    1988-10-01

    The 1980 International Labour Office (ILO) classification of posteroanterior chest radiographs was used to obtain the scores for profusion of small opacities and pleural abnormalities of 172 men with confirmed or suspected disease of the lungs due to asbestos. After allowance had been made for age, stature, and smoking habit the quantitative score for area of diffuse pleural thickening seen in profile on both lateral chest walls contributed to reductions in inspiratory capacity, expiratory reserve volume, and forced expiratory flow rates. Occlusion of one or both costophrenic angles in the presence of diffuse thickening was associated with further reduction in inspiratory capacity. Profusion of small opacities was associated with a reduction in transfer factor. Diffuse pleural thickening and occlusion of costophrenic angles were associated with relatively low values for the forced expiratory flow rates (MEF50FVC) and FEV1/FVC, whereas small opacities were associated with relatively high values. Thus overall increased, normal, or reduced values of MEF50FVC and FEV1/FVC might occur, depending on the distribution of the radiographic abnormalities. The findings contribute to the validation of the ILO pleural scores; those for diffuse pleural thickening and occlusion of costophrenic angles should be used jointly with the scores for profusion of parenchymal small opacities in interpreting the lung function of persons exposed to asbestos.

  5. Relationship of lung function to radiographic reading (ILO) in patients with asbestos related lung disease.

    PubMed Central

    Cotes, J E; King, B

    1988-01-01

    The 1980 International Labour Office (ILO) classification of posteroanterior chest radiographs was used to obtain the scores for profusion of small opacities and pleural abnormalities of 172 men with confirmed or suspected disease of the lungs due to asbestos. After allowance had been made for age, stature, and smoking habit the quantitative score for area of diffuse pleural thickening seen in profile on both lateral chest walls contributed to reductions in inspiratory capacity, expiratory reserve volume, and forced expiratory flow rates. Occlusion of one or both costophrenic angles in the presence of diffuse thickening was associated with further reduction in inspiratory capacity. Profusion of small opacities was associated with a reduction in transfer factor. Diffuse pleural thickening and occlusion of costophrenic angles were associated with relatively low values for the forced expiratory flow rates (MEF50FVC) and FEV1/FVC, whereas small opacities were associated with relatively high values. Thus overall increased, normal, or reduced values of MEF50FVC and FEV1/FVC might occur, depending on the distribution of the radiographic abnormalities. The findings contribute to the validation of the ILO pleural scores; those for diffuse pleural thickening and occlusion of costophrenic angles should be used jointly with the scores for profusion of parenchymal small opacities in interpreting the lung function of persons exposed to asbestos. PMID:3206385

  6. Image-based modeling of lung structure and function

    PubMed Central

    Tawhai, Merryn H.; Lin, Ching-Long

    2010-01-01

    Current state-of-the-art in image-based modeling allows derivation of patient-specific models of the lung, lobes, airways, and pulmonary vascular trees. The application of traditional engineering analyses of fluid and structural mechanics to image-based subject-specific models has the potential to provide new insight into structure-function relationships in the individual via functional interpretation that complements imaging and experimental studies. Three major issues that are encountered in studies of air flow through the bronchial airways are the representation of airway geometry, the imposition of physiological boundary conditions, and the treatment of turbulence. Here we review some efforts to resolve each of these issues, with particular focus on image-based models that have been developed to simulate air flow from the mouth to the terminal bronchiole, and subjected to physiologically meaningful boundary conditions via image registration and soft tissue mechanics models. PMID:21105146

  7. 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.

  8. Lung fibroblasts accelerate wound closure in human alveolar epithelial cells through hepatocyte growth factor/c-Met signaling

    PubMed Central

    Correll, Kelly; Schiel, John A.; Finigan, Jay H.; Prekeris, Rytis; Mason, Robert J.

    2014-01-01

    There are 190,600 cases of acute lung injury/acute respiratory distress syndrome (ALI/ARDS) each year in the United States, and the incidence and mortality of ALI/ARDS increase dramatically with age. Patients with ALI/ARDS have alveolar epithelial injury, which may be worsened by high-pressure mechanical ventilation. Alveolar type II (ATII) cells are the progenitor cells for the alveolar epithelium and are required to reestablish the alveolar epithelium during the recovery process from ALI/ARDS. Lung fibroblasts (FBs) migrate and proliferate early after lung injury and likely are an important source of growth factors for epithelial repair. However, how lung FBs affect epithelial wound healing in the human adult lung has not been investigated in detail. Hepatocyte growth factor (HGF) is known to be released mainly from FBs and to stimulate both migration and proliferation of primary rat ATII cells. HGF is also increased in lung tissue, bronchoalveolar lavage fluid, and serum in patients with ALI/ARDS. Therefore, we hypothesized that HGF secreted by FBs would enhance wound closure in alveolar epithelial cells (AECs). Wound closure was measured using a scratch wound-healing assay in primary human AEC monolayers and in a coculture system with FBs. We found that wound closure was accelerated by FBs mainly through HGF/c-Met signaling. HGF also restored impaired wound healing in AECs from the elderly subjects and after exposure to cyclic stretch. We conclude that HGF is the critical factor released from FBs to close wounds in human AEC monolayers and suggest that HGF is a potential strategy for hastening alveolar repair in patients with ALI/ARDS. PMID:24748602

  9. Prediction of postoperative loss of lung function in patients with malignant lung mass. Quantitative regional ventilation-perfusion scanning

    SciTech Connect

    Ryo, U.Y. )

    1990-05-01

    The quantitative measurement of regional ventilation and perfusion distribution is simply and reliably accomplished by using routinely available radioactive gas and perfusion lung scanning agents, and a large field-of-view gamma camera with an on-line computer. The preoperative prediction of postsurgical loss in lung function can be made accurately by using the quantitative ventilation-perfusion lung scan technique. Either a regional ventilation study or perfusion study may be used for the prediction, but analysis of regional ventilation distribution appears to be a better parameter than that of perfusion distribution for the prediction of postoperative loss of FEV1. In the rare case of a patient with a marked ventilation-perfusion deficit, quantitative distribution of both ventilation and perfusion may be needed for an accurate assessment of postsurgical lung function. 18 references.

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

    PubMed

    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

  11. 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

  12. 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.

  13. 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

  14. Diazoxide accelerates wound healing by improving EPC function.

    PubMed

    Li, Zhang-Peng; Xin, Ru-Juan; Yang, Hong; Jiang, Guo-Jun; Deng, Ya-Ping; Li, Dong-Jie; Shen, Fu-Ming

    2016-01-01

    Endothelial cell dysfunction is the primary cause of microvascular complications in diabetes. Diazoxide enables beta cells to rest by reversibly suppressing glucose-induced insulin secretion by opening ATP-sensitive K+ channels in the beta cells. This study investigated the role of diazoxide in wound healing in mice with streptozotocin (STZ)-induced diabetes and explored the possible mechanisms of its effect. Compared to the controls, mice with STZ-induced diabetes exhibited significantly impaired wound healing. Diazoxide treatment (30 mg/kg/d, intragastrically) for 28 days accelerated wound closure and stimulated angiogenesis in the diabetic mice. Circulating endothelial progenitor cells (EPCs) increased significantly in the diazoxide-treated diabetic mice. The adhesion, migration, and tube formation abilities of bone marrow (BM)-EPCs were impaired by diabetes, and these impairments were improved by diazoxide treatment. The expression of both p53 and TSP-1 increased in diabetic mice compared to that in the controls, and these increases were inhibited significantly by diazoxide treatment. In vitro, diazoxide treatment improved the impaired BM-EPC function and diminished the increased expression of p53 and TSP-1 in cultured BM-EPCs caused by high glucose levels. We conclude that diazoxide improved BM-EPC function in mice with STZ-induced diabetes, possibly via a p53- and TSP-1-dependent pathway. PMID:27100489

  15. 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

  16. A longitudinal study of lung function in jute processing workers.

    PubMed

    Liu, Z; Zhou, C; Lou, J

    1992-01-01

    A 5-y follow-up study of pulmonary function was conducted in 1982 and in 1987 for 50 current and retired jute-processing workers who had been employed for more than 10 y in a jute mill in China. Control subjects, who had no history of dust or gas exposure, were selected from a paper-packing plant in the same city. Forced expiratory maneuvers were conducted in the same manner in both 1982 and 1987. The jute workers' pulmonary functions, i.e., forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1.0), and forced expiratory flow (FEF25-75%), were more compromised than were pulmonary functions in the controls for the same 5-y period; however, only the increased incidence of abnormal FEV1.0s in jute workers was statistically significant. Male jute workers had significantly higher annual decrements of FVC, FEV1.0, and FEF25-75% than did control workers. Regression analysis indicated that in 1987, predicted values of FEV1.0 and FEF25-75% for the jute workers were related to years of employment. Our results suggest that long-term exposure to jute dust could produce chronic loss of lung function.

  17. Acute effects of routine firefighting on lung function.

    PubMed

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

    1986-01-01

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

  18. 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

  19. Effect of lung transplantation on diaphragmatic function in patients with chronic obstructive pulmonary disease.

    PubMed Central

    Wanke, T.; Merkle, M.; Formanek, D.; Zifko, U.; Wieselthaler, G.; Zwick, H.; Klepetko, W.; Burghuber, O. C.

    1994-01-01

    BACKGROUND--To date there are no data on the effects of lung transplantation on diaphragmatic function in patients with end stage chronic obstructive pulmonary disease (COPD). It is not known whether the relation between the transdiaphragmatic pressure (PDI) and lung volume is altered in recipients after transplantation as a result of changes in diaphragmatic structure caused by chronic hyperinflation. The effect of lung transplantation on diaphragmatic strength was determined in patients with COPD and the relation between postoperative PDI and lung volume analysed. METHODS--Diaphragmatic strength was assessed in eight double lung transplant recipients, six single lung transplant recipients, and in 14 patients with COPD whose lung function was similar to those of the transplant recipients preoperatively. PDI obtained during unilateral and bilateral phrenic nerve stimulation at 1 Hz (twitch PDI) at functional residual capacity (FRC) and during maximal sniff manoeuvres (sniff PDI) at various levels of inspiratory vital capacity (VCin) served as parameters for diaphragmatic strength. Sniff PDI assessed at the various VCin levels were used to analyse the PDI/lung volume relation. RESULTS--Lung transplantation caused a reduction in lung volume, especially in the double lung transplant recipients. As a consequence sniff PDI was higher in the double lung transplant recipients than in the patients with COPD at all levels of VCin analysed. However, sniff PDI values analysed at comparable intrathoracic gas volumes were not reduced in the patients with COPD when compared with those who underwent lung transplantation. Bilateral twitch PDI values were similar in the patients with COPD and in the lung transplant recipients. In the single lung transplant recipients unilateral twitch PDI values were similar on the transplanted and the non-transplanted side. The relation between PDI and lung volume was similar in the patients with COPD and in the lung transplant recipients

  20. 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. PMID:26540298

  1. 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.

  2. 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

  3. Effective avoidance of a functional spect-perfused lung using intensity modulated radiotherapy (IMRT) for non-small cell lung cancer (NSCLC): an update of a planning study.

    PubMed

    Lavrenkov, Konstantin; Singh, Shalini; Christian, Judith A; Partridge, Mike; Nioutsikou, Elena; Cook, Gary; Bedford, James L; Brada, Michael

    2009-06-01

    IMRT and 3-dimensional conformal radiotherapy (3-DCRT) plans of 25 patients with non-small cell lung (NSCLC) were compared in terms of planning target volume (PTV) coverage and sparing of functional lung (FL) defined by a SPECT perfusion scan. IMRT resulted in significant reduction of functional V(20) and mean lung dose in stage III patients with inhomogeneous hypoperfusion. If the dose to FL is shown to be the determinant of lung toxicity, IMRT would allow for effective dose escalation by specific avoidance of functional lung. PMID:18995919

  4. Gallic acid induces apoptosis in EGFR-mutant non-small cell lung cancers by accelerating EGFR turnover.

    PubMed

    Nam, Boas; Rho, Jin Kyung; Shin, Dong-Myung; Son, Jaekyoung

    2016-10-01

    Gallic acid is a common botanic phenolic compound, which is present in plants and foods worldwide. Gallic acid is implicated in various biological processes such as cell growth and apoptosis. Indeed, gallic acid has been shown to induce apoptosis in many cancer types. However, the molecular mechanisms of gallic acid-induced apoptosis in cancer, particularly lung cancer, are still unclear. Here, we report that gallic acid induces apoptosis in EGFR-mutant non-small cell lung cancer (NSCLC) cells, but not in EGFR-WT NSCLC cells. Treatment with gallic acid resulted in a significant reduction in proliferation and induction of apoptosis, only in EGFR-mutant NSCLC cells. Interestingly, treatment with gallic acid led to a robust decrease in EGFR levels, which is critical for NSCLC survival. Treatment with gallic acid had no significant effect on transcription, but induced EGFR turnover. Indeed, treatment with a proteasome inhibitor dramatically reversed gallic acid-induced EGFR downregulation. Moreover, treatment with gallic acid induced EGFR turnover leading to apoptosis in EGFR-TKI (tyrosine kinase inhibitor)-resistant cell lines, which are dependent on EGFR signaling for survival. Thus, these studies suggest that gallic acid can induce apoptosis in EGFR-dependent lung cancers that are dependent on EGFR for growth and survival via acceleration of EGFR turnover.

  5. Gallic acid induces apoptosis in EGFR-mutant non-small cell lung cancers by accelerating EGFR turnover.

    PubMed

    Nam, Boas; Rho, Jin Kyung; Shin, Dong-Myung; Son, Jaekyoung

    2016-10-01

    Gallic acid is a common botanic phenolic compound, which is present in plants and foods worldwide. Gallic acid is implicated in various biological processes such as cell growth and apoptosis. Indeed, gallic acid has been shown to induce apoptosis in many cancer types. However, the molecular mechanisms of gallic acid-induced apoptosis in cancer, particularly lung cancer, are still unclear. Here, we report that gallic acid induces apoptosis in EGFR-mutant non-small cell lung cancer (NSCLC) cells, but not in EGFR-WT NSCLC cells. Treatment with gallic acid resulted in a significant reduction in proliferation and induction of apoptosis, only in EGFR-mutant NSCLC cells. Interestingly, treatment with gallic acid led to a robust decrease in EGFR levels, which is critical for NSCLC survival. Treatment with gallic acid had no significant effect on transcription, but induced EGFR turnover. Indeed, treatment with a proteasome inhibitor dramatically reversed gallic acid-induced EGFR downregulation. Moreover, treatment with gallic acid induced EGFR turnover leading to apoptosis in EGFR-TKI (tyrosine kinase inhibitor)-resistant cell lines, which are dependent on EGFR signaling for survival. Thus, these studies suggest that gallic acid can induce apoptosis in EGFR-dependent lung cancers that are dependent on EGFR for growth and survival via acceleration of EGFR turnover. PMID:27597244

  6. An expert system for synoptic interpretation of lung function tests.

    PubMed

    Heise, D; Kroker, P; Mailänder, A

    1990-01-01

    We simulate the interpretation process by the testing of preformed working hypotheses. A clinical syndrome, "bronchial obstruction," is described by a set of suitable parameters (FEV1, MMEF, Raw, etc.). For a given patient, this set forms a normalized vector. It has to be compared with equivalent data derived from patients which fulfilled the criteria for the clinical syndrome in question. If the patient's vector has a similar direction as the vector of the collective, the working hypothesis is accepted. The length of the vector is then used to quantify the severity of the functional disturbances in verbal terms ("slight," "moderate," "severe"). The limits used for severity grading and the typical parameter pattern for the given syndrome are adapted to the user's criteria by a built-in learning capability. On the other hand, the assembled data may be used for the training of newcomers. The use of vector algorithms allows for a high flexibility of our program with respect to all methods used in lung function testing. PMID:2117121

  7. An expert system for synoptic interpretation of lung function tests.

    PubMed

    Heise, D; Kroker, P; Mailänder, A

    1990-01-01

    We simulate the interpretation process by the testing of preformed working hypotheses. A clinical syndrome, "bronchial obstruction," is described by a set of suitable parameters (FEV1, MMEF, Raw, etc.). For a given patient, this set forms a normalized vector. It has to be compared with equivalent data derived from patients which fulfilled the criteria for the clinical syndrome in question. If the patient's vector has a similar direction as the vector of the collective, the working hypothesis is accepted. The length of the vector is then used to quantify the severity of the functional disturbances in verbal terms ("slight," "moderate," "severe"). The limits used for severity grading and the typical parameter pattern for the given syndrome are adapted to the user's criteria by a built-in learning capability. On the other hand, the assembled data may be used for the training of newcomers. The use of vector algorithms allows for a high flexibility of our program with respect to all methods used in lung function testing.

  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. 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.

  10. 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

  11. 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

  12. Validity of Body-Worn Sensor Acceleration Metrics to Index Upper Extremity Function in Hemiparetic Stroke

    PubMed Central

    Urbin, M.A.; Bailey, Ryan R.; Lang, Catherine E.

    2015-01-01

    Background and Purpose In people with stroke, real-world use of the paretic upper extremity influences function. Therefore, measures of real-world use are of value for guiding rehabilitation. We undertook a study to identify the acceleration characteristics that have a stable association with upper extremity function and sensitivity to within-participant fluctuations in function over multiple sessions of task-specific training. Methods Twenty-seven adults > 6 months post stroke with upper extremity paresis participated. Signals from wrist-worn accelerometers were sampled at 30 Hz during seven sessions of task-specific training. Paretic upper extremity function was evaluated with the Action Research Arm Test (ARAT). We used Spearman correlations to examine within-session associations between acceleration metrics and ARAT performance. A mixed model was used to determine which metrics were sensitive to within-participant fluctuations in upper extremity function across the seven training sessions. Results Upper extremity function correlated with bilateral acceleration variability and use ratio during five and six session, respectively. Time accelerating between 76-100% of peak acceleration correlated with function in six sessions. Variability of the paretic upper extremity acceleration and the ratio of acceleration variability between upper extremities were associated with function during all seven sessions. Variability in both the acceleration of the paretic upper extremity, and acceleration of the paretic and non-paretic extremities combined were sensitive to within-participant fluctuations in function across training sessions. Conclusion Multiple features of the acceleration profile track with upper extremity function within and across sessions of task-specific training. It may be possible to monitor these features with accelerometers to index upper extremity function outside of clinical settings. PMID:25742378

  13. Functional repair of human donor lungs by IL-10 gene therapy.

    PubMed

    Cypel, Marcelo; Liu, Mingyao; Rubacha, Matt; Yeung, Jonathan C; Hirayama, Shin; Anraku, Masaki; Sato, Masaaki; Medin, Jeffrey; Davidson, Beverly L; de Perrot, Marc; Waddell, Thomas K; Slutsky, Arthur S; Keshavjee, Shaf

    2009-10-28

    More than 80% of potential donor lungs are injured during brain death of the donor and from complications experienced in the intensive care unit, and therefore cannot be used for transplantation. These lungs show inflammation and disruption of the alveolar-capillary barrier, leading to poor gas exchange. Although the number of patients in need of lung transplantation is increasing, the number of donors is static. We investigated the potential to use gene therapy with an adenoviral vector encoding human interleukin-10 (AdhIL-10) to repair injured donor lungs ex vivo before transplantation. IL-10 is an anti-inflammatory cytokine that mainly exerts its suppressive functions by the inactivation of antigen-presenting cells with consequent inhibition of proinflammatory cytokine secretion. In pigs, AdhIL-10-treated lungs exhibited attenuated inflammation and improved function after transplantation. Lungs from 10 human multiorgan donors that had suffered brain death were determined to be clinically unsuitable for transplantation. They were then maintained for 12 hours at body temperature in an ex vivo lung perfusion system with or without intra-airway delivery of AdhIL-10 gene therapy. AdhIL-10-treated lungs showed significant improvement in function (arterial oxygen pressure and pulmonary vascular resistance) when compared to controls, a favorable shift from proinflammatory to anti-inflammatory cytokine expression, and recovery of alveolar-blood barrier integrity. Thus, treatment of injured human donor lungs with the cytokine IL-10 can improve lung function, potentially rendering injured lungs suitable for transplantation into patients. PMID:20368171

  14. Long-Term Exposure to Traffic Emissions and Fine Particulate Matter and Lung Function Decline in the Framingham Heart Study

    PubMed Central

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

    2015-01-01

    Rationale: Few studies have examined associations between long-term exposure to fine particulate matter (PM2.5) and lung function decline in adults. Objectives: To determine if exposure to traffic and PM2.5 is associated with longitudinal changes in lung function in a population-based cohort in the Northeastern United States, where pollution levels are relatively low. Methods: FEV1 and FVC were measured up to two times between 1995 and 2011 among 6,339 participants of the Framingham Offspring or Third Generation studies. We tested associations between residential proximity to a major roadway and PM2.5 exposure in 2001 (estimated by a land-use model using satellite measurements of aerosol optical thickness) and lung function. We examined differences in average lung function using mixed-effects models and differences in lung function decline using linear regression models. Current smokers were excluded. Models were adjusted for age, sex, height, weight, pack-years, socioeconomic status indicators, cohort, time, season, and weather. Measurements and Main Results: Living less than 100 m from a major roadway was associated with a 23.2 ml (95% confidence interval [CI], −44.4 to −1.9) lower FEV1 and a 5.0 ml/yr (95% CI, −9.0 to −0.9) faster decline in FEV1 compared with more than 400 m. Each 2 μg/m3 increase in average of PM2.5 was associated with a 13.5 ml (95% CI, −26.6 to −0.3) lower FEV1 and a 2.1 ml/yr (95% CI, −4.1 to −0.2) faster decline in FEV1. There were similar associations with FVC. Associations with FEV1/FVC ratio were weak or absent. Conclusions: Long-term exposure to traffic and PM2.5, at relatively low levels, was associated with lower FEV1 and FVC and an accelerated rate of lung function decline. PMID:25590631

  15. 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.

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

    ClinicalTrials.gov

    2015-03-17

    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

  17. Nitric oxide synthase polymorphisms, gene expression and lung function in chronic obstructive pulmonary disease

    PubMed Central

    2013-01-01

    Background Due to the pleiotropic effects of nitric oxide (NO) within the lungs, it is likely that NO is a significant factor in the pathogenesis of chronic obstructive pulmonary disease (COPD). The aim of this study was to test for association between single nucleotide polymorphisms (SNPs) in three NO synthase (NOS) genes and lung function, as well as to examine gene expression and protein levels in relation to the genetic variation. Methods One SNP in each NOS gene (neuronal NOS (NOS1), inducible NOS (NOS2), and endothelial NOS (NOS3)) was genotyped in the Lung Health Study (LHS) and correlated with lung function. One SNP (rs1800779) was also analyzed for association with COPD and lung function in four COPD case–control populations. Lung tissue expression of NOS3 mRNA and protein was tested in individuals of known genotype for rs1800779. Immunohistochemistry of lung tissue was used to localize NOS3 expression. Results For the NOS3 rs1800779 SNP, the baseline forced expiratory volume in one second in the LHS was significantly higher in the combined AG + GG genotypic groups compared with the AA genotypic group. Gene expression and protein levels in lung tissue were significantly lower in subjects with the AG + GG genotypes than in AA subjects. NOS3 protein was expressed in the airway epithelium and subjects with the AA genotype demonstrated higher NOS3 expression compared with AG and GG individuals. However, we were not able to replicate the associations with COPD or lung function in the other COPD study groups. Conclusions Variants in the NOS genes were not associated with lung function or COPD status. However, the G allele of rs1800779 resulted in a decrease of NOS3 gene expression and protein levels and this has implications for the numerous disease states that have been associated with this polymorphism. PMID:24192154

  18. 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

  19. Hyperpolarized 129Xe MRI: A Viable Functional Lung Imaging Modality?

    PubMed Central

    Patz, Samuel; Hersman, F. William; Muradian, Iga; Hrovat, Mirko I.; Ruset, Iulian C.; Ketel, Stephen; Jacobson, Francine; Topulos, George P.; Hatabu, Hiroto; Butler, James P.

    2008-01-01

    The majority of researchers investigating hyperpolarized gas MRI as a candidate functional lung imaging modality have used 3He as their imaging agent of choice rather than 129Xe. This preference has been predominantly due to, 3He providing stronger signals due to higher levels of polarization and higher gyromagnetic ratio, as well as its being easily available to more researchers due to availability of polarizers (USA) or ease of gas transport (Europe). Most researchers agree, however, that hyperpolarized 129Xe will ultimately emerge as the imaging agent of choice due to its unlimited supply in nature and its falling cost. Our recent polarizer technology delivers vast improvements in hyperpolarized 129Xe output. Using this polarizer, we have demonstrated the unique property of xenon to measure alveolar surface area noninvasively. In this article, we describe our human protocols and their safety, and our results for the measurement of the partial pressure of pulmonary oxygen (pO2) by observation of 129Xe signal decay. We note that the measurement of pO2 by observation of 129Xe signal decay is more complex than that for 3He because of an additional signal loss mechanism due to interphase diffusion of 129Xe from alveolar gas spaces to septal tissue. This results in measurements of an equivalent pO2 that accounts for both traditional T1 decay from pO2 and that from interphase diffusion. We also provide an update on new technological advancements that form the foundation for an improved compact design polarizer as well as improvements that provide another order-of-magnitude scale-up in xenon polarizer output. PMID:17890035

  20. 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).

  1. 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

  2. Polymorphisms in the ß2 adrenergic receptor and bronchodilator response, bronchial hyperresponsiveness, and rate of decline in lung function in smokers

    PubMed Central

    Joos, L; Weir, T; Connett, J; Anthonisen, N; Woods, R; Pare, P; Sandford, A

    2003-01-01

    Methods: The prevalence of two ADRB2 polymorphisms, Arg16→Gly and Gln27→Glu, was examined in 587 smokers chosen from the NHLBI Lung Health Study for having the fastest (n=282) and slowest (n=305) 5 year rate of decline in forced expiratory volume in 1 second (FEV1; mean ΔFEV1 -4.14 and +1.08% predicted/year, respectively). Results: Contrary to our hypothesis, no ADRB2 allele or haplotype was associated with NSBH, BDR, or rate of decline in lung function. However, there was a significant negative association between heterozygosity at position 27 and a fast decline in lung function (adjusted odds ratio 0.56, 95% CI 0.40 to 0.78, p=0.0007). Conclusions: Heterozygosity at position 27 may be protective against an accelerated rate of decline in lung function. The polymorphism at position 16 does not contribute to the rate of decline in lung function, measures of NSBH, or BDR in smokers. PMID:12885990

  3. Functional expression of the transient receptor potential channel TRPA1, a sensor for toxic lung inhalants, in pulmonary epithelial cells.

    PubMed

    Büch, Thomas Robert Heinrich; Schäfer, Eva Anna Maria; Demmel, Maria-Theresia; Boekhoff, Ingrid; Thiermann, Horst; Gudermann, Thomas; Steinritz, Dirk; Schmidt, Annette

    2013-12-01

    The cation channel TRPA1 functions as a chemosensory protein and is directly activated by a number of noxious inhalants. A pulmonary expression of TRPA1 has been described in sensory nerve endings and its stimulation leads to the acceleration of inflammatory responses in the lung. Whereas the function of TRPA1 in neuronal cells is well defined, only few reports exist suggesting a role in epithelial cells. The aim of the present study was therefore (1) to evaluate the expression of TRPA1 in pulmonary epithelial cell lines, (2) to characterize TRPA1-promoted signaling in these cells, and (3) to study the extra-neuronal expression of this channel in lung tissue sections. Our results revealed that the widely used alveolar type II cell line A549 expresses TRPA1 at the mRNA and protein level. Furthermore, stimulating A549 cells with known TRPA1 activators (i.e., allyl isothiocyanate) led to an increase in intracellular calcium levels, which was sensitive to the TRPA1 blocker ruthenium red. Investigating TRPA1 coupled downstream signaling cascades it was found that TRPA1 activation elicited a stimulation of ERK1/2 whereas other MAP kinases were not affected. Finally, using epithelial as well as neuronal markers in immunohistochemical approaches, a non-neuronal TRPA1 protein expression was detected in distal parts of the porcine lung epithelium, which was also found examining human lung sections. TRPA1-positive staining co-localized with both epithelial and neuronal markers underlining the observed epithelial expression pattern. Our findings of a functional expression of TRPA1 in pulmonary epithelial cells provide causal evidence for a non-neuronal TRPA1-mediated control of inflammatory responses elicited upon TRPA1-mediated registration of toxic inhalants in vivo. PMID:23994502

  4. 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...

  5. Corticosteroids and surfactant change lung function and protein leaks in the lungs of ventilated premature rabbits.

    PubMed Central

    Ikegami, M; Berry, D; elKady, T; Pettenazzo, A; Seidner, S; Jobe, A

    1987-01-01

    Fetal rabbits were treated with corticosteroids by maternal administration for 48 h before delivery at 27 d gestational age. The treated and control rabbits were placed on ventilator-plethysmographs so that ventilation could be adjusted by regulation of tidal volumes to 10-13 ml/kg body wt. [125I]albumin was mixed with fetal lung fluid at birth, alternate rabbits from each litter were treated with Surfactant-TA, and [131I]albumin was injected intravascularly. The movement of the labeled albumins into and out of the alveolar wash and lung tissue was measured after 30 min of ventilation. Corticosteroid treatment (total dose, 0.2 mg/kg betamethasone) significantly decreased the protein leak across the endothelium (P less than 0.001) but increased the protein leak across the epithelium (P less than 0.001). Surfactant treatment decreased both the endothelial and epithelial leaks, and the combination of surfactant and corticosteroid treatments decreased endothelial leaks to 29% of control values and increased compliance more than either treatment alone. The 48-h corticosteroid treatment did not increase alveolar surfactant pool sizes. Corticosteroids significantly changed lung protein leaks independently of surfactant, and improved the response of the preterm lung to surfactant treatments. PMID:3571492

  6. Signal transduction mediated by endostatin directly modulates cellular function of lung cancer cells in vitro.

    PubMed

    Cui, Ri; Ohashi, Rina; Takahashi, Fumiyuki; Yoshioka, Masakata; Tominaga, Shigeru; Sasaki, Shinichi; Gu, Tao; Takagi, Yumiko; Takahashi, Kazuhisa

    2007-06-01

    Endostatin (ED) is a carboxyl-terminal fragment of collagen XVIII with strong antiangiogenic activity. ED has been considered as a highly specific inhibitor of endothelial cell proliferation and migration through interaction with its receptor on the surface of endothelial cells. Recently, direct antitumor effects of ED in colon cancer cells and head and neck squamous cell carcinoma cells has been reported. However, its effect on lung cancer cells has not been clarified. The purpose of the present study was to determine the effect of ED on in vitro lung cancer cell function and to identify its receptor on lung cancer cells. We revealed that alpha5 integrin is capable of being a functional ED receptor among several integrins that are expressed on murine lung cancer (Lewis lung cancer [LLC]) cells. We further demonstrated that the ED-integrin interaction modulates various in vitro biological functions of LLC cells as we revealed that immobilized ED helps in LLC cell adhesion and migration in an integrin-dependent manner. Furthermore, ED inhibited LLC cell proliferation and induced apoptosis. Interestingly, ED did not demonstrate any antiproliferative activity against the other murine lung cancer cell line, KLN205, that lacks alpha5 integrin but binds to immobilized ED through the beta1 integrin. In addition, the binding of ED to alpha5 integrin on LLC cells induced phosphorylation of focal adhesion kinase. Taken together, these results suggest that the interaction between ED and alpha5 integrin may play an important role in lung cancer cell function.

  7. Relationship Between Functional Exercise Capacity and Lung Functions in Obese Chidren

    PubMed Central

    Özgen, İlker Tolga; Çakır, Erkan; Torun, Emel; Güleş, Alper; Hepokur, Merve Nur; Cesur, Yaşar

    2015-01-01

    Objective: Cardiovascular, respiratory and musculoskeletal system disorders which may affect the functional exercise capacity are common in obese patients. We aimed to investigate the functional exercise capacity and its relationship with functional pulmonary capacity in obese children. Methods: A total of 74 obese and 36 healthy children as a control group were enrolled in the study. Pulmonary functions and functional exercise capacity were measured by spirometry and six-minute walk test (6 MWT), respectively. Results: The distances covered during the 6 MWT in obese and control groups were 570.9±67.5 and 607.8±72.5 meters, respectively (p=0.010). In spirometric pulmonary function tests (PFTs), forced expiratory volume in 1 sec (FEV1) and forced mid-expiratory flows (25-75) were lower in the obese group (p=0.048 and p=0.047, respectively), whereas forced vital capacity (FVC), the FEV1/FVC ratio and peak expiratory flow were not statistically different between the obese and control groups. Multiple regression analysis revealed that among all parameters of anthropometric measures and PFTs, only body mass index standard deviation score (BMI-SDS) was the independent factor influencing 6 MWT. Conclusion: Functional exercise and lung capacities of obese children were diminished as compared to those of non-obese children. The most important factor influencing functional exercise capacity was BMI-SDS. PMID:26831556

  8. Intermedin Stabilized Endothelial Barrier Function and Attenuated Ventilator-induced Lung Injury in Mice

    PubMed Central

    Müller-Redetzky, Holger Christian; Kummer, Wolfgang; Pfeil, Uwe; Hellwig, Katharina; Will, Daniel; Paddenberg, Renate; Tabeling, Christoph; Hippenstiel, Stefan; Suttorp, Norbert; Witzenrath, Martin

    2012-01-01

    Background Even protective ventilation may aggravate or induce lung failure, particularly in preinjured lungs. Thus, new adjuvant pharmacologic strategies are needed to minimize ventilator-induced lung injury (VILI). Intermedin/Adrenomedullin-2 (IMD) stabilized pulmonary endothelial barrier function in vitro. We hypothesized that IMD may attenuate VILI-associated lung permeability in vivo. Methodology/Principal Findings Human pulmonary microvascular endothelial cell (HPMVEC) monolayers were incubated with IMD, and transcellular electrical resistance was measured to quantify endothelial barrier function. Expression and localization of endogenous pulmonary IMD, and its receptor complexes composed of calcitonin receptor-like receptor (CRLR) and receptor activity-modifying proteins (RAMPs) 1–3 were analyzed by qRT-PCR and immunofluorescence in non ventilated mouse lungs and in lungs ventilated for 6 h. In untreated and IMD treated mice, lung permeability, pulmonary leukocyte recruitment and cytokine levels were assessed after mechanical ventilation. Further, the impact of IMD on pulmonary vasoconstriction was investigated in precision cut lung slices (PCLS) and in isolated perfused and ventilated mouse lungs. IMD stabilized endothelial barrier function in HPMVECs. Mechanical ventilation reduced the expression of RAMP3, but not of IMD, CRLR, and RAMP1 and 2. Mechanical ventilation induced lung hyperpermeability, which was ameliorated by IMD treatment. Oxygenation was not improved by IMD, which may be attributed to impaired hypoxic vasoconstriction due to IMD treatment. IMD had minor impact on pulmonary leukocyte recruitment and did not reduce cytokine levels in VILI. Conclusions/Significance IMD may possibly provide a new approach to attenuate VILI. PMID:22563471

  9. 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.

  10. Perinatal stress and early life programming of lung structure and function

    PubMed Central

    Wright, Rosalind J.

    2010-01-01

    Exposure to environmental toxins during critical periods of prenatal and/or postnatal development may alter the normal course of lung morphogenesis and maturation, potentially resulting in changes that affect both structure and function of the respiratory system. Moreover, these early effects may persist into adult life magnifying the potential public health impact. Aberrant or excessive pro-inflammatory immune responses, occurring both locally and systemically, that result in inflammatory damage to the airway are a central determinant of lung structure-function changes throughout life. Disruption of neuroendocrine function in early development, specifically the hypothalamic-pituitary-adrenal (HPA) axis, may alter functional status of the immune system. Autonomic nervous system (ANS) function (sympathovagal imbalance) is another integral component of airway function and immunity in childhood. This overview discusses the evidence linking psychological factors to alterations in these interrelated physiological processes that may, in turn, influence childhood lung function and identifies gaps in our understanding. PMID:20080145

  11. Lung disease

    MedlinePlus

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

  12. [Birth weight as a factor determining lung function among healthy persons and its relation with chronic pulmonary disease].

    PubMed

    Ichnowski, Jerzy; Lindner, Karolina; Pawłowicz, Robert; Panaszek, Bernard

    2012-01-01

    Low lung function is associated with increased risk of morbidity and mortality in the population. Lung development seems to be important factor in pathogenesis of respiratory disorders. Airway development is a complex process. Birth weight (BW) is one of perinatal factors which influences development of pulmonary system and multiorgan function of the body. Aforementioned relationships are visible especially at first years of life. However, not very many studies have examined the associations between birth weight and lung function in later age then childhood and adolescence. The aim of this review is to discuss relationships between BW and lung function parameters in healthy individuals and patients with lung disease in childhood and adulthood.

  13. 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

  14. 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.

  15. 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

  16. 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

  17. Use of senescence-accelerated mouse model in bleomycin-induced lung injury suggests that bone marrow-derived cells can alter the outcome of lung injury in aged mice.

    PubMed

    Xu, Jianguo; Gonzalez, Edilson T; Iyer, Smita S; Mac, Valerie; Mora, Ana L; Sutliff, Roy L; Reed, Alana; Brigham, Kenneth L; Kelly, Patricia; Rojas, Mauricio

    2009-07-01

    The incidence of pulmonary fibrosis increases with age. Studies from our group have implicated circulating progenitor cells, termed fibrocytes, in lung fibrosis. In this study, we investigate whether the preceding determinants of inflammation and fibrosis were augmented with aging. We compared responses to intratracheal bleomycin in senescence-accelerated prone mice (SAMP), with responses in age-matched control senescence-accelerated resistant mice (SAMR). SAMP mice demonstrated an exaggerated inflammatory response as evidenced by lung histology. Bleomycin-induced fibrosis was significantly higher in SAMP mice compared with SAMR controls. Consistent with fibrotic changes in the lung, SAMP mice expressed higher levels of transforming growth factor-beta1 in the lung. Furthermore, SAMP mice showed higher numbers of fibrocytes and higher levels of stromal cell-derived factor-1 in the peripheral blood. This study provides the novel observation that apart from increases in inflammatory and fibrotic factors in response to injury, the increased mobilization of fibrocytes may be involved in age-related susceptibility to lung fibrosis. PMID:19359440

  18. Advances in functional and structural imaging of the human lung using proton MRI.

    PubMed

    Miller, G Wilson; Mugler, John P; Sá, Rui C; Altes, Talissa A; Prisk, G Kim; Hopkins, Susan R

    2014-12-01

    The field of proton lung MRI is advancing on a variety of fronts. In the realm of functional imaging, it is now possible to use arterial spin labeling (ASL) and oxygen-enhanced imaging techniques to quantify regional perfusion and ventilation, respectively, in standard units of measurement. By combining these techniques into a single scan, it is also possible to quantify the local ventilation-perfusion ratio, which is the most important determinant of gas-exchange efficiency in the lung. To demonstrate potential for accurate and meaningful measurements of lung function, this technique was used to study gravitational gradients of ventilation, perfusion, and ventilation-perfusion ratio in healthy subjects, yielding quantitative results consistent with expected regional variations. Such techniques can also be applied in the time domain, providing new tools for studying temporal dynamics of lung function. Temporal ASL measurements showed increased spatial-temporal heterogeneity of pulmonary blood flow in healthy subjects exposed to hypoxia, suggesting sensitivity to active control mechanisms such as hypoxic pulmonary vasoconstriction, and illustrating that to fully examine the factors that govern lung function it is necessary to consider temporal as well as spatial variability. Further development to increase spatial coverage and improve robustness would enhance the clinical applicability of these new functional imaging tools. In the realm of structural imaging, pulse sequence techniques such as ultrashort echo-time radial k-space acquisition, ultrafast steady-state free precession, and imaging-based diaphragm triggering can be combined to overcome the significant challenges associated with proton MRI in the lung, enabling high-quality three-dimensional imaging of the whole lung in a clinically reasonable scan time. Images of healthy and cystic fibrosis subjects using these techniques demonstrate substantial promise for non-contrast pulmonary angiography and detailed

  19. 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

  20. [Liposome phospholipid substitution and lung function in surfactant deprived rats].

    PubMed

    Obladen, M

    1985-01-01

    In vivo activity of an artificial surfactant was studied in surfactant depleted rats. After tenfold alveolar lavage, PaO2, tidal volume, and compliance of the respiratory system fell to one third of initial value. Substitution of large unilamellar vesicles containing 90% Dipalmitoylphosphatidylcholine and 10% unsaturated phosphatidylglycerol largely restored oxygenation and lung mechanics in most animals. Complete normalization with weaning from the ventilator, however, was achieved neither with liposomes nor with natural surfactant concentrate.

  1. Nuclear Receptor Expression and Function in Human Lung Cancer Pathogenesis

    PubMed Central

    Kim, Jihye; Sato, Mitsuo; Choi, Jong-Whan; Kim, Hyun-Won; Yeh, Byung-Il; Larsen, Jill E.; Minna, John D.; Cha, Jeong-Heon; Jeong, Yangsik

    2015-01-01

    Lung cancer is caused by combinations of diverse genetic mutations. Here, to understand the relevance of nuclear receptors (NRs) in the oncogene-associated lung cancer pathogenesis, we investigated the expression profile of the entire 48 NR members by using QPCR analysis in a panel of human bronchial epithelial cells (HBECs) that included precancerous and tumorigenic HBECs harboring oncogenic K-rasV12 and/or p53 alterations. The analysis of the profile revealed that oncogenic alterations accompanied transcriptional changes in the expression of 19 NRs in precancerous HBECs and 15 NRs according to the malignant progression of HBECs. Amongst these, peroxisome proliferator-activated receptor gamma (PPARγ), a NR chosen as a proof-of-principle study, showed increased expression in precancerous HBECs, which was surprisingly reversed when these HBECs acquired full in vivo tumorigenicity. Notably, PPARγ activation by thiazolidinedione (TZD) treatment reversed the increased expression of pro-inflammatory cyclooxygenase 2 (COX2) in precancerous HBECs. In fully tumorigenic HBECs with inducible expression of PPARγ, TZD treatments inhibited tumor cell growth, clonogenecity, and cell migration in a PPARγ-sumoylation dependent manner. Mechanistically, the sumoylation of liganded-PPARγ decreased COX2 expression and increased 15-hydroxyprostaglandin dehydrogenase expression. This suggests that ligand-mediated sumoylation of PPARγ plays an important role in lung cancer pathogenesis by modulating prostaglandin metabolism. PMID:26244663

  2. Effect of caffeine on respiratory muscle strength and lung function in prematurely born, ventilated infants.

    PubMed

    Kassim, Zainab; Greenough, Anne; Rafferty, Gerrard F

    2009-12-01

    The aims of this study were to determine whether caffeine administration increased respiratory muscle function and if this was associated with lung function improvement in prematurely born infants being weaned from mechanical ventilation. Respiratory muscle function was assessed by measurement of the maximum pressures generated during occlusions at end inspiration (Pemax) and end expiration (Pimax) and lung function by measurement of lung volume (functional residual capacity (FRC)) and respiratory system compliance (CRS) and resistance (RRS) in 18 infants with a median gestational age of 28 (range 24-36) weeks. Measurements were made immediately prior to caffeine administration (baseline) and 6 h later. Six hours after caffeine administration compared to baseline, the median Pemax (p = 0.017), Pimax (p = 0.004), FRC (p < 0.001), CRS (p = 0.002) and RRS (p = 0.004) had significantly improved. Our results suggest that caffeine administration facilitates weaning of prematurely born infants from mechanical ventilation by improving respiratory muscle strength.

  3. Lung function testing in COPD: when everything is not so simple

    PubMed Central

    Barisione, Giovanni; Brusasco, Claudia; Garlaschi, Alessandro; Crimi, Emanuele; Brusasco, Vito

    2014-01-01

    Combined pulmonary fibrosis and emphysema is a condition occurring mainly in male smokers, presenting different lung mechanics and gas exchange abnormalities than emphysema or pulmonary fibrosis alone. We report the case of an elderly man, former heavy smoker, who presented with progressive exertional dyspnea for 1 year. Lung function tests showed near normal spirometry and lung volumes but marked reduction of diffusing capacity for carbon monoxide and even more nitric oxide. The arterial partial pressure of oxygen was reduced with a markedly increased alveolar-to-arterial difference. High-resolution computed tomography of the chest showed a pattern consistent with upper lobe emphysema and lower lobe pulmonary fibrosis. In conclusion, this case report confirms the limitations of a simplistic approach to lung function in the diagnosis of symptomatic smokers. PMID:25530864

  4. Changes in lung function during adolescence in athletes and non-athletes.

    PubMed

    Lakhera, S C; Kain, T C; Bandopadhyay, P

    1994-09-01

    The purpose of this study was to evaluate the lung function in Indian athletes and non-athletes during adolescence. For this, lung functions in 40 boys (twenty athletes and twenty non-athletes) in the age range of 13 to 16 years, were evaluated over a period of two years at yearly intervals. The variables studied were Forced Vital Capacity (FVC), Forced Expiratory Volume in one second (FEV1), Expiratory Reserve Volume (ERV), Inspiratory Capacity (IC) and Maximum Voluntary Ventilation (MVV). Our results suggest that the development of the lung during adolescence under proper nutritional and health conditions is governed by the process of growth with no or negligible additional effects of physical activity. It is summarized that physical activity during growth may increase endurance in respiratory muscles. However, the findings of this study does not reject the possibility that lung size may increase by a strenuous and prolonged strength training regimen during adolescence.

  5. Lung function in relation to silicosis and silica exposure in granite workers.

    PubMed

    Ng, T P; Chan, S L

    1992-09-01

    Lung function tests (forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and FEV1/FVC %) were related to silica exposure and the extent of radiological opacities in a study of 206 active and 132 previously employed granite workers from two quarries. The investigations included detailed personal interviews, spirometric testing and radiographic examination of the chest. The chest X-ray films were read randomly and independently by three readers, using International Labour Office (ILO) standard films. Cumulative exposure to respirable silica (mg.m-3-yr) and total granite dust (million particles per cubic foot (mppcf-yr)) were estimated for each subject based on his years of employment at various jobs and historical and current measurements of quarry-, period- and job-specific exposures. The results suggest that chronic simple silicosis, especially for profusion category 2 and 3, was associated with significant lung function loss. As expected, mixed dust fibrosis was associated with little or no functional disturbance. Massive fibrosis was associated with significant obstructive and restrictive impairment. No additional effect of exposure to respirable silica on lung function loss was found after allowing for the presence of "silicosis". However, exposure to total dust (mppcf-yr) appeared to be associated with some lung function loss independent of silicosis. Our results indicate that chronic simple silicosis is not a benign disease; silica exposure is the primary cause, but the lung function loss in silicotics is directly attributable to the fibrotic lung disease. However, exposure to total granite dust beyond the respirable size range may separately produce additional lung function loss.

  6. The relation of circulating CC16 to lung function growth, decline, and development of COPD across the lifespan

    PubMed Central

    Guerra, Stefano; Halonen, Marilyn; Vasquez, Monica M; Spangenberg, Amber; Stern, Debra A.; Morgan, Wayne J.; Wright, Anne L.; Lavi, Iris; Tarès, Lluïsa; Carsin, Anne-Elie; Dobaño, Carlota; Barreiro, Esther; Zock, Jan-Paul; Martínez-Moratalla, Jesús; Urrutia, Isabel; Sunyer, Jordi; Keidel, Dirk; Imboden, Medea; Probst-Hensch, Nicole; Hallberg, Jenny; Melén, Erik; Wickman, Magnus; Bousquet, Jean; Belgrave, Danielle C. M.; Simpson, Angela; Custovic, Adnan; Antó, Josep M; Martinez, Fernando D

    2015-01-01

    Background Low serum levels of the anti-inflammatory club cell secretory protein (CC16) have been associated with an accelerated FEV1 decline in COPD. Whether low circulating CC16 precedes lung function deficits and incidence of COPD in the general population is unknown. Methods We used longitudinal data from adults who were COPD-free at baseline from the population-based TESAOD (N=960, mean follow-up: 14yrs), ECRHS-Sp (N=514, 11yrs) and SAPALDIA (N=167, 8yrs) studies. CC16 was measured in serum from baseline and associated with subsequent FEV1 decline and incidence of airflow limitation. To evaluate early life CC16 effects, we also measured circulating CC16 in samples from ages 4-6yrs to predict subsequent lung function in childhood in the CRS (N=427), MAAS (N=481), and BAMSE (N=231) birth cohorts. Findings In adults – after adjustment for sex, age, height, smoking status/intensity, pack-years, asthma, and initial FEV1 levels – baseline CC16 was inversely associated with subsequent decline of FEV1 in TESAOD (p=0.0014), ECRHS-Sp (p=0.023), and a similar trend was found in SAPALDIA (p=0.052). Low CC16 at baseline also predicted an increased risk for incident stage 2 airflow limitation (i.e., FEV1/FVC<70% plus FEV1 % predicted < 80%) in TESAOD and ECRHS-Sp. In children, the lowest tertile of CC16 at age 4–6yrs was associated with subsequent FEV1 deficits up to age 16yrs (meta-analyzed estimate from adjusted models on birth cohorts: −68ml, p=0.0001). Results were confirmed among subjects who never smoked by age 16yrs (−71ml, p<0.0001). Interpretation Low serum CC16 is associated with subsequent slower growth and accelerated decline of lung function, and increased risk of developing stage 2 airflow limitation. Funding US National Heart, Lung, and Blood Institute and EU Seventh Framework Programme. For a complete list of other funding agencies, please refer to the acknowledgements section of the paper. PMID:26159408

  7. 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

  8. Accelerated Hypofractionated Radiotherapy for Early-Stage Non-Small-Cell Lung Cancer: Long-Term Results

    SciTech Connect

    Soliman, Hany; Cheung, Patrick; Yeung, Latifa; Poon, Ian; Balogh, Judith; Barbera, Lisa; Spayne, Jacqueline; Danjoux, Cyril; Dahele, Max; Ung, Yee

    2011-02-01

    Purpose: To retrospectively review the results of a single-institution series of accelerated hypofractionated radiotherapy for early-stage non-small-cell lung cancer (NSCLC) in patients who are medically inoperable or who refuse surgery. Methods and Materials: Peripherally located T1 to T3 N0 M0 tumors were treated with 48 to 60 Gy in 12 to 15 fractions between 1996 and 2007. No elective nodal irradiation was delivered. Patient, tumor, and treatment information was abstracted from the medical records. Results: A total of 124 tumors were treated in 118 patients (56 male and 62 female). Median age at diagnosis was 76.3 years (range, 49-90 years). In all, 113 patients (95.8%) were not surgical candidates because of medical comorbidities. The 2- and 5-year overall survival (OS) rates were 51.0% and 23.3%, respectively, and the 2- and 5-year cause-specific survival (CSS) rates were 67.6% and 59.8%, respectively. The 2- and 5-year actuarial local control (LC) rates were 76.2% and 70.1%, respectively. Univariate analysis revealed that tumor size less than 3cm compared with greater than 3 cm resulted in significantly improved OS (40.0% vs. 5.0% at 5 years; p = 0.0002), CSS (69.7% vs. 45.1% at 5 years; p = 0.0461), and a trend toward better LC (82.5% vs. 66.9% at 2 years, 76.6% vs. 60.8% at 5 years; p = 0.0685). Treatment was well tolerated and there were no treatment delays because of acute toxicity. Conclusions: Accelerated hypofractionated radiotherapy with 48 to 60 Gy using fractions of 4 Gy per day provides very good results for small tumors in medically inoperable patients with early-stage NSCLC.

  9. Serum Methylarginines and Spirometry-Measured Lung Function in Older Adults

    PubMed Central

    McEvoy, Mark A.; Schofield, Peter W.; Smith, Wayne T.; Agho, Kingsley; Mangoni, Arduino A.; Soiza, Roy L.; Peel, Roseanne; Hancock, Stephen J.; Carru, Ciriaco; Zinellu, Angelo; Attia, John R.

    2013-01-01

    Rationale Methylarginines are endogenous nitric oxide synthase inhibitors that have been implicated in animal models of lung disease but have not previously been examined for their association with spirometric measures of lung function in humans. Objectives This study measured serum concentrations of asymmetric and symmetric dimethylarginine in a representative sample of older community-dwelling adults and determined their association with spirometric lung function measures. Methods Data on clinical, lifestyle, and demographic characteristics, methylated arginines, and L-arginine (measured using LC-MS/MS) were collected from a population-based sample of older Australian adults from the Hunter Community Study. The five key lung function measures included as outcomes were Forced Expiratory Volume in 1 second, Forced Vital Capacity, Forced Expiratory Volume in 1 second to Forced Vital Capacity ratio, Percent Predicted Forced Expiratory Volume in 1 second, and Percent Predicted Forced Vital Capacity. Measurements and Main Results In adjusted analyses there were statistically significant independent associations between a) higher asymmetric dimethylarginine, lower Forced Expiratory Volume in 1 second and lower Forced Vital Capacity; and b) lower L-arginine/asymmetric dimethylarginine ratio, lower Forced Expiratory Volume in 1 second, lower Percent Predicted Forced Expiratory Volume in 1 second and lower Percent Predicted Forced Vital Capacity. By contrast, no significant associations were observed between symmetric dimethylarginine and lung function. Conclusions After adjusting for clinical, demographic, biochemical, and pharmacological confounders, higher serum asymmetric dimethylarginine was independently associated with a reduction in key measures of lung function. Further research is needed to determine if methylarginines predict the decline in lung function. PMID:23690915

  10. Effect of Second-Hand Smoke Exposure on Lung Function among Non-Smoking Korean Women

    PubMed Central

    KIM, Youngmee; CHO, Won-Kyung; EVANGELISTA, Lorraine S.

    2013-01-01

    Abstract Background Previous literature has implicated that there might be an individual susceptibility difference in terms of race/ethnicity and gender in response to second hand smoke (SHS) exposure. This study was done to examine the effect of SHS exposure on lung function in non-smoking Korean women. Methods This cross-sectional study was conducted using the Korea National Health and Nutrition Examination Survey (KNHANES) from 2008-2011. A total of 2,513 female participants, age 40 yr and older, with no respiratory symptoms or prior lung diseases, were included in this study. Participants’ smoking status was examined using both self-reported history and measurement of urinary cotinine level. Lung function was assessed using spirometry data, including FVC and FEV1. T-test and Chi-square tests were performed to compare diverse variables between groups. Analysis of covariance (ANCOVA) adjusted for age, height, alcohol consumption, and level of exercise was used to see any statistical differences in lung function parameters between non-SHS exposed and SHS-exposed groups. Results Among 2,513 non-smoking females, 767 (30.5%) were SHS-exposed. The urinary cotinine levels clearly distinguished SHS exposure, and the mean urinary cotinine levels were 7.1±0.4 and 11±0.7 in non-SHS exposed group vs. SHS-exposed group, respectively (P < 0.001). Urinary cotinine levels were correlated with duration of SHS exposure. However, both groups had normal lung function and there was no significant difference between the two groups in lung function. Conclusions Urinary cotinine is a valuable marker of SHS exposure. Korean women may have higher tolerance for SHS exposure-induced lung function decline. PMID:26060638

  11. Functional Validation and Comparison Framework for EIT Lung Imaging

    PubMed Central

    Meybohm, Patrick; Weiler, Norbert; Frerichs, Inéz; Adler, Andy

    2014-01-01

    Introduction Electrical impedance tomography (EIT) is an emerging clinical tool for monitoring ventilation distribution in mechanically ventilated patients, for which many image reconstruction algorithms have been suggested. We propose an experimental framework to assess such algorithms with respect to their ability to correctly represent well-defined physiological changes. We defined a set of clinically relevant ventilation conditions and induced them experimentally in 8 pigs by controlling three ventilator settings (tidal volume, positive end-expiratory pressure and the fraction of inspired oxygen). In this way, large and discrete shifts in global and regional lung air content were elicited. Methods We use the framework to compare twelve 2D EIT reconstruction algorithms, including backprojection (the original and still most frequently used algorithm), GREIT (a more recent consensus algorithm for lung imaging), truncated singular value decomposition (TSVD), several variants of the one-step Gauss-Newton approach and two iterative algorithms. We consider the effects of using a 3D finite element model, assuming non-uniform background conductivity, noise modeling, reconstructing for electrode movement, total variation (TV) reconstruction, robust error norms, smoothing priors, and using difference vs. normalized difference data. Results and Conclusions Our results indicate that, while variation in appearance of images reconstructed from the same data is not negligible, clinically relevant parameters do not vary considerably among the advanced algorithms. Among the analysed algorithms, several advanced algorithms perform well, while some others are significantly worse. Given its vintage and ad-hoc formulation backprojection works surprisingly well, supporting the validity of previous studies in lung EIT. PMID:25110887

  12. 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. PMID:27125385

  13. [Changes in lung function testing associated with obesity].

    PubMed

    Carpio, Carlos; Santiago, Ana; García de Lorenzo, Abelardo; Alvarez-Sala, Rodolfo

    2014-11-01

    Excess bodyweight has an important impact on the physiology of breathing. In fact, it affects resting lung volumes and exercise capacity. These effects appear as a consequence of ventilatory and inflammatory changes commonly associated to obesity. As a result, obese individuals have a rapid and shallow pattern of breathing, their respiratory compliance is reduced and the airway resistance tends to be higher. However, with respect to aerobic capacity, contradictory results have been reported depending on the way peak oxygen uptake is expressed. Moreover, the inability of this population to achieve maximal efforts during exercise testing also affects their cardiorespiratory fitness.

  14. 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.

  15. Inhaled corticosteroids and lower lung function decline in young children with cystic fibrosis.

    PubMed

    De Boeck, K; Vermeulen, F; Wanyama, S; Thomas, M

    2011-05-01

    A recent American registry analysis in cystic fibrosis (CF) children showed less lung function decline after starting inhaled corticosteroid (ICS) use. We therefore examined the influence of ICS treatment on lung function in Belgian CF patients. Data from patients ≥ 6 yrs of age were eligible, provided entries on lung function, height and ICS use were available in two consecutive years. Data after oral steroid use or transplant were excluded. 852 subjects contributed data with 2,976 data pairs analysed, 44.9% concerning years of ICS use. Yearly % predicted decline in forced expiratory volume in 1 s (FEV₁) was 1.07% lower during ICS use (p = 0.001). Subgroup analysis for age revealed that the lower FEV₁ decline rate during ICS use was only statistically significant in children 6-12 yrs of age (2.56%; p = 0.0003). Baseline FEV(1) was lower by 5.89% (p < 0.0001) in ICS users for all age groups combined, but there was no difference in baseline lung function in the children 6-12 yrs of age. In 6-12-yr-old children with CF, baseline lung function was similar in ICS users and nonusers, but annualised FEV₁ decline was 2.56% pred lower in ICS users. Our data therefore support recent American findings. PMID:21071470

  16. 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

  17. 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.

  18. Lung function and exhaled nitric oxide in healthy unsedated African infants

    PubMed Central

    Gray, Diane; Willemse, Lauren; Visagie, Ane; Smith, Emilee; Czövek, Dorottya; Sly, Peter D; Hantos, Zoltán; Hall, Graham L; Zar, Heather J

    2015-01-01

    Background and objective Population-appropriate lung function reference data are essential to accurately identify respiratory disease and measure response to interventions. There are currently no reference data in African infants. The aim was to describe normal lung function in healthy African infants. Methods Lung function was performed on healthy South African infants enrolled in a birth cohort study, the Drakenstein child health study. Infants were excluded if they were born preterm or had a history of neonatal respiratory distress or prior respiratory tract infection. Measurements, made during natural sleep, included the forced oscillation technique, tidal breathing, exhaled nitric oxide and multiple breath washout measures. Results Three hundred sixty-three infants were tested. Acceptable and repeatable measurements were obtained in 356 (98%) and 352 (97%) infants for tidal breathing analysis and exhaled nitric oxide outcomes, 345 (95%) infants for multiple breath washout and 293 of the 333 (88%) infants for the forced oscillation technique. Age, sex and weight-for-age z score were significantly associated with lung function measures. Conclusions This study provides reference data for unsedated infant lung function in African infants and highlights the importance of using population-specific data. PMID:26134556

  19. Breathlessness in elderly individuals is related to low lung function and reversibility of airway obstruction.

    PubMed

    Boezen, H M; Rijcken, B; Schouten, J P; Postma, D S

    1998-10-01

    The perception of breathlessness is a subject-related factor which is linked to respiratory disease, cardiac disease and overweight. We studied the distribution of breathlessness, its association with respiratory disease, cardiac disease and overweight, as well as its association with lung function, reversibility of airway obstruction ("reversibility") and peak expiratory flow (PEF) variability in an elderly population. Data on breathlessness (rated with Borg scale), lung function, reversibility, PEF variability, respiratory symptoms, cardiac disease and overweight were collected in a random sample of 210 elderly (>55 yrs old) who participated in a physical fitness test. Individuals with a Borg score >0 were taken to have breathlessness. Subjects with a Borg score >0 (n=50, 24%) were three to five times more likely to have a low lung function and large reversibility than subjects with a Borg score of zero, independent of the presence of respiratory symptoms, cardiac disease or overweight, although these three factors were all associated with low lung function and a large reversibility and PEF variability. Reversibility was not associated with PEF variability whatsoever. In elderly individuals, breathlessness is frequently present. Assessment of breathlessness using the Borg-scale seems an important clinical measurement, because it is an important independent predictor of lung function impairment in the elderly.

  20. 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...

  1. In vitro particulate matter exposure causes direct and lung-mediated indirect effects on cardiomyocyte function

    PubMed Central

    Gorr, Matthew W.; Youtz, Dane J.; Eichenseer, Clayton M.; Smith, Korbin E.; Nelin, Timothy D.; Cormet-Boyaka, Estelle

    2015-01-01

    Particulate matter (PM) exposure induces a pathological response from both the lungs and the cardiovascular system. PM is capable of both manifestation into the lung epithelium and entrance into the bloodstream. Therefore, PM has the capacity for both direct and lung-mediated indirect effects on the heart. In the present studies, we exposed isolated rat cardiomyocytes to ultrafine particulate matter (diesel exhaust particles, DEP) and examined their contractile function and calcium handling ability. In another set of experiments, lung epithelial cells (16HBE14o- or Calu-3) were cultured on permeable supports that allowed access to both the basal (serosal) and apical (mucosal) media; the basal media was used to culture cardiomyocytes to model the indirect, lung-mediated effects of PM on the heart. Both the direct and indirect treatments caused a reduction in contractility as evidenced by reduced percent sarcomere shortening and reduced calcium handling ability measured in field-stimulated cardiomyocytes. Treatment of cardiomyocytes with various anti-oxidants before culture with DEP was able to partially prevent the contractile dysfunction. The basal media from lung epithelial cells treated with PM contained several inflammatory cytokines, and we found that monocyte chemotactic protein-1 was a key trigger for cardiomyocyte dysfunction. These results indicate the presence of both direct and indirect effects of PM on cardiomyocyte function in vitro. Future work will focus on elucidating the mechanisms involved in these separate pathways using in vivo models of air pollution exposure. PMID:25957217

  2. 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.

  3. The EPICure Study: Association between Hemodynamics and Lung Function at 11 Years after Extremely Preterm Birth

    PubMed Central

    Bolton, Charlotte E.; Stocks, Janet; Hennessy, Enid; Cockcroft, John R.; Fawke, Joseph; Lum, Sooky; McEniery, Carmel M.; Wilkinson, Ian B.; Marlow, Neil

    2012-01-01

    Objective To investigate the relationship between disturbed lung function and large-artery hemodynamics in school-age children born extremely preterm (EP) (at 25 completed weeks of gestation or less). Study design This was a cross-sectional study of participants from the EPICure study, now aged 11 years (n = 66), and 86 age- and sex-matched term-born classmates. Spirometry parameters (including forced expiratory volume in 1 second), blood pressure, and augmentation index (AIx, a composite of arterial stiffness and global wave reflections) were measured. Results Compared with their classmates, the EP children had significantly impaired lung function, particularly those with neonatal bronchopulmonary dysplasia. Peripheral blood pressure did not differ significantly between the 2 groups, but AIx values were on average 5% higher (95% CI, 2%-8%) in the preterm infants, remaining significant after adjustment for potential confounders. Neonatal bronchopulmonary dysplasia status was not related to AIx. Lung function and maternal smoking were independently associated with AIx; AIx increased by 2.7% per z-score reduction in baseline forced expiratory volume in 1 second and by 4.9% in those whose mothers smoked during pregnancy. Conclusion The independent association between impaired lung function and cardiovascular physiology in early adolescence implies higher cardiovascular risk for children born EP, and suggests that prevention of chronic neonatal lung disease may be a priority in reducing later cardiovascular risk in preterm infants. PMID:22575246

  4. 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

  5. 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.

  6. 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.

  7. Long-chain Acylcarnitines Reduce Lung Function by Inhibiting Pulmonary Surfactant.

    PubMed

    Otsubo, Chikara; Bharathi, Sivakama; Uppala, Radha; Ilkayeva, Olga R; Wang, Dongning; McHugh, Kevin; Zou, Ye; Wang, Jieru; Alcorn, John F; Zuo, Yi Y; Hirschey, Matthew D; Goetzman, Eric S

    2015-09-25

    The role of mitochondrial energy metabolism in maintaining lung function is not understood. We previously observed reduced lung function in mice lacking the fatty acid oxidation enzyme long-chain acyl-CoA dehydrogenase (LCAD). Here, we demonstrate that long-chain acylcarnitines, a class of lipids secreted by mitochondria when metabolism is inhibited, accumulate at the air-fluid interface in LCAD(-/-) lungs. Acylcarnitine accumulation is exacerbated by stress such as influenza infection or by dietary supplementation with l-carnitine. Long-chain acylcarnitines co-localize with pulmonary surfactant, a unique film of phospholipids and proteins that reduces surface tension and prevents alveolar collapse during breathing. In vitro, the long-chain species palmitoylcarnitine directly inhibits the surface adsorption of pulmonary surfactant as well as its ability to reduce surface tension. Treatment of LCAD(-/-) mice with mildronate, a drug that inhibits carnitine synthesis, eliminates acylcarnitines and improves lung function. Finally, acylcarnitines are detectable in normal human lavage fluid. Thus, long-chain acylcarnitines may represent a risk factor for lung injury in humans with dysfunctional fatty acid oxidation.

  8. Athletes, yogis and individuals with sedentary lifestyles; do their lung functions differ?

    PubMed

    Prakash, Shivesh; Meshram, Sushant; Ramtekkar, Ujjwal

    2007-01-01

    Buffalo health study concluded that pulmonary function is a long-term predictor for overall survival rates. It is essential to be involved in physical activity or sports which help in achieving better lung function. Cross sectional observation study was conducted to determine if yoga and athletic activity (running) are associated with better lung functions as compared to subjects with sedentary lifestyles and how does athletes and yogis differ in lung function. Spirometric parameters were assessed in randomly selected 60 healthy male, non-smoking; non-obese subjects-athletes, yogis and sedentary workers. The groups differed significantly in FEV1 and PEFR. The highest mean FEV1 and PEFR were observed in yogis. Both yogis and athletes had significantly better FEV1 as compared to sedentary workers. Yogis also had significantly better PEFR as compared to sedentary workers and athletes. Yogis and athletes had similar lung functions except for better PEFR amongst yogis. Involvement in daily physical activity or sport preferably yoga can help in achieving better pulmonary function.

  9. Genome-wide association study of lung function decline in adults with and without asthma

    PubMed Central

    Imboden, Medea; Bouzigon, Emmanuelle; Curjuric, Ivan; Ramasamy, Adaikalavan; Kumar, Ashish; Hancock, Dana B; Wilk, Jemma B; Vonk, Judith M; Thun, Gian A; Siroux, Valerie; Nadif, Rachel; Monier, Florent; Gonzalez, Juan R; Wjst, Matthias; Heinrich, Joachim; Loehr, Laura R; Franceschini, Nora; North, Kari E; Altmüller, Janine; Koppelman, Gerard H.; Guerra, Stefano; Kronenberg, Florian; Lathrop, Mark; Moffatt, Miriam F; O’Connor, George T; Strachan, David P; Postma, Dirkje S; London, Stephanie J; Schindler, Christian; Kogevinas, Manolis; Kauffmann, Francine; Jarvis, Debbie L; Demenais, Florence; Probst-Hensch, Nicole M

    2012-01-01

    Background Genome-wide association studies (GWAS) have identified determinants of chronic obstructive pulmonary disease, asthma and lung function level, however none addressed decline in lung function. Aim We conducted the first GWAS on age-related decline in forced expiratory volume in the first second (FEV1) and in its ratio to forced vital capacity (FVC) stratified a priori by asthma status. Methods Discovery cohorts included adults of European ancestry (1441 asthmatics, 2677 non-asthmatics; Epidemiological Study on the Genetics and Environment of Asthma (EGEA); Swiss Cohort Study on Air Pollution And Lung And Heart Disease In Adults (SAPALDIA); European Community Respiratory Health Survey (ECRHS)). The associations of FEV1 and FEV1/FVC decline with 2.5 million single nucleotide polymorphisms (SNPs) were estimated. Thirty loci were followed-up by in silico replication (1160 asthmatics, 10858 non-asthmatics: Atherosclerosis Risk in Communities (ARIC); Framingham Heart Study (FHS); British 1958 Birth Cohort (B58C); Dutch asthma study). Results Main signals identified differed between asthmatics and non-asthmatics. None of the SNPs reached genome-wide significance. The association between the height related gene DLEU7 and FEV1 decline suggested for non-asthmatics in the discovery phase was replicated (discovery P=4.8×10−6; replication P=0.03) and additional sensitivity analyses point to a relation to growth. The top ranking signal, TUSC3, associated with FEV1/FVC decline in asthmatics (P=5.3×10−8) did not replicate. SNPs previously associated with cross-sectional lung function were not prominently associated with decline. Conclusions Genetic heterogeneity of lung function may be extensive. Our results suggest that genetic determinants of longitudinal and cross-sectional lung function differ and vary by asthma status. PMID:22424883

  10. SERPINA1 PiZ and PiS Heterozygotes and Lung Function Decline in the SAPALDIA Cohort

    PubMed Central

    Thun, Gian-Andri; Ferrarotti, Ilaria; Imboden, Medea; Rochat, Thierry; Gerbase, Margaret; Kronenberg, Florian; Bridevaux, Pierre-Olivier; Zemp, Elisabeth; Zorzetto, Michele; Ottaviani, Stefania; Russi, Erich W.; Luisetti, Maurizio; Probst-Hensch, Nicole M.

    2012-01-01

    Background Severe alpha1-antitrypsin (AAT) deficiency is a strong risk factor for COPD. But the impact of gene variants resulting in mild or intermediate AAT deficiency on the longitudinal course of respiratory health remains controversial. There is indication from experimental studies that pro-inflammatory agents like cigarette smoke can interact with these variants and thus increase the risk of adverse respiratory health effects. Therefore, we tested the effect of the presence of a protease inhibitor (Pi) S or Z allele (PiMS and PiMZ) on the change in lung function in different inflammation-exposed subgroups of a large, population-based cohort study. Methodology and Principal Findings The SAPALDIA population includes over 4600 subjects from whom SERPINA1 genotypes for S and Z alleles, spirometry and respiratory symptoms at baseline and after 11 years follow-up, as well as proxies for inflammatory conditions, such as detailed smoking history, obesity and high sensitivity C-reactive protein (hs-CRP), were available. All analyses were performed by applying multivariate regression models. There was no overall unfavourable effect of PiMS or PiMZ genotype on lung function change. We found indication that PiZ heterozygosity interacted with inflammatory stimuli leading to an accelerated decline in measures in use as indices for assessing mild airway obstruction. Obese individuals with genotype PiMM had an average annual decline in the forced mid expiratory flow (ΔFEF25-75%) of 58.4 ml whereas in obese individuals with PiMZ it amounted to 92.2 ml (p = 0.03). Corresponding numbers for persistent smokers differed even more strongly (66.8 ml (PiMM) vs. 108.2 ml (PiMZ), p = 0.005). Equivalent, but less strong associations were observed for the change in the FEV1/FVC ratio. Conclusions We suggest that, in addition to the well established impact of the rare PiZZ genotype, one Z allele may be sufficient to accelerate lung function decline in population subgroups

  11. 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.

  12. Regulation and function of antimicrobial peptides in immunity and diseases of the lung.

    PubMed

    Seiler, Frederik; Lepper, Philipp Moritz; Bals, Robert; Beisswenger, Christoph

    2014-04-01

    Cationic antimicrobial peptides (AMPs) are among the best studied antimicrobial factors expressed in the respiratory tract. AMPs are released by epithelial cells and immune cells into the airway surface liquid covering the epithelial surfaces of the lung where they act as endogenous antibiotics. Plenty of studies showed that AMPs possess additional, often immunomodulatory functions besides their antimicrobial activities. AMPs are chemotactic for immune cells and modulate cellular mechanisms, such as proliferation of epithelial cells, epithelial regeneration, and angiogenesis. The expression and activity of AMPs are impacted by lung diseases and AMPs can have adverse effects in lung diseases. In this review, we discuss the regulation and functions of AMPs in host defense and respiratory tract diseases.

  13. Sex differences in relations of muscle power, lung function, and reaction time in athletes.

    PubMed

    Gursoy, Recep

    2010-06-01

    In an earlier study, relations of nonverbal abilities with several bodily measures such as height, weight, and lung capacity were observed. The present aim was estimation of associations of muscle power and lung function with simple eye-hand reaction time. Sex differences for muscle power were significant even with the covariates of height, weight, and age included; however, these disappeared for lung functions (forced vital capacity and peak expiratory flow) and reaction time. The effects of leg power, forced vital capacity, and peak expiratory flow on the left eye-hand reaction time were significant after adjustment for height, weight, right- and left-hand powers and age. The positive effect of exercise may be especially associated with the right brain activity or left hand speed.

  14. Head and Tibial Acceleration as a Function of Stride Frequency and Visual Feedback during Running.

    PubMed

    Busa, Michael A; Lim, Jongil; van Emmerik, Richard E A; Hamill, Joseph

    2016-01-01

    Individuals regulate the transmission of shock to the head during running at different stride frequencies although the consequences of this on head-gaze stability remain unclear. The purpose of this study was to examine if providing individuals with visual feedback of their head-gaze orientation impacts tibial and head accelerations, shock attenuation and head-gaze motion during preferred speed running at different stride frequencies. Fifteen strides from twelve recreational runners running on a treadmill at their preferred speed were collected during five stride frequencies (preferred, ±10% and ±20% of preferred) in two visual task conditions (with and without real-time visual feedback of head-gaze orientation). The main outcome measures were tibial and head peak accelerations assessed in the time and frequency domains, shock attenuation from tibia to head, and the magnitude and velocity of head-gaze motion. Decreasing stride frequency resulted in greater vertical accelerations of the tibia (p<0.01) during early stance and at the head (p<0.01) during early and late stance; however, for the impact portion the increase in head acceleration was only observed for the slowest stride frequency condition. Visual feedback resulted in reduced head acceleration magnitude (p<0.01) and integrated power spectral density in the frequency domain (p<0.01) in late stance, as well as overall of head-gaze motion (p<0.01). When running at preferred speed individuals were able to stabilize head acceleration within a wide range of stride frequencies; only at a stride frequency 20% below preferred did head acceleration increase. Furthermore, impact accelerations of the head and tibia appear to be solely a function of stride frequency as no differences were observed between feedback conditions. Increased visual task demands through head gaze feedback resulted in reductions in head accelerations in the active portion of stance and increased head-gaze stability.

  15. Head and Tibial Acceleration as a Function of Stride Frequency and Visual Feedback during Running

    PubMed Central

    Busa, Michael A.; Lim, Jongil; van Emmerik, Richard E. A.; Hamill, Joseph

    2016-01-01

    Individuals regulate the transmission of shock to the head during running at different stride frequencies although the consequences of this on head-gaze stability remain unclear. The purpose of this study was to examine if providing individuals with visual feedback of their head-gaze orientation impacts tibial and head accelerations, shock attenuation and head-gaze motion during preferred speed running at different stride frequencies. Fifteen strides from twelve recreational runners running on a treadmill at their preferred speed were collected during five stride frequencies (preferred, ±10% and ±20% of preferred) in two visual task conditions (with and without real-time visual feedback of head-gaze orientation). The main outcome measures were tibial and head peak accelerations assessed in the time and frequency domains, shock attenuation from tibia to head, and the magnitude and velocity of head-gaze motion. Decreasing stride frequency resulted in greater vertical accelerations of the tibia (p<0.01) during early stance and at the head (p<0.01) during early and late stance; however, for the impact portion the increase in head acceleration was only observed for the slowest stride frequency condition. Visual feedback resulted in reduced head acceleration magnitude (p<0.01) and integrated power spectral density in the frequency domain (p<0.01) in late stance, as well as overall of head-gaze motion (p<0.01). When running at preferred speed individuals were able to stabilize head acceleration within a wide range of stride frequencies; only at a stride frequency 20% below preferred did head acceleration increase. Furthermore, impact accelerations of the head and tibia appear to be solely a function of stride frequency as no differences were observed between feedback conditions. Increased visual task demands through head gaze feedback resulted in reductions in head accelerations in the active portion of stance and increased head-gaze stability. PMID:27271850

  16. Head and Tibial Acceleration as a Function of Stride Frequency and Visual Feedback during Running.

    PubMed

    Busa, Michael A; Lim, Jongil; van Emmerik, Richard E A; Hamill, Joseph

    2016-01-01

    Individuals regulate the transmission of shock to the head during running at different stride frequencies although the consequences of this on head-gaze stability remain unclear. The purpose of this study was to examine if providing individuals with visual feedback of their head-gaze orientation impacts tibial and head accelerations, shock attenuation and head-gaze motion during preferred speed running at different stride frequencies. Fifteen strides from twelve recreational runners running on a treadmill at their preferred speed were collected during five stride frequencies (preferred, ±10% and ±20% of preferred) in two visual task conditions (with and without real-time visual feedback of head-gaze orientation). The main outcome measures were tibial and head peak accelerations assessed in the time and frequency domains, shock attenuation from tibia to head, and the magnitude and velocity of head-gaze motion. Decreasing stride frequency resulted in greater vertical accelerations of the tibia (p<0.01) during early stance and at the head (p<0.01) during early and late stance; however, for the impact portion the increase in head acceleration was only observed for the slowest stride frequency condition. Visual feedback resulted in reduced head acceleration magnitude (p<0.01) and integrated power spectral density in the frequency domain (p<0.01) in late stance, as well as overall of head-gaze motion (p<0.01). When running at preferred speed individuals were able to stabilize head acceleration within a wide range of stride frequencies; only at a stride frequency 20% below preferred did head acceleration increase. Furthermore, impact accelerations of the head and tibia appear to be solely a function of stride frequency as no differences were observed between feedback conditions. Increased visual task demands through head gaze feedback resulted in reductions in head accelerations in the active portion of stance and increased head-gaze stability. PMID:27271850

  17. 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.

  18. 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

  19. Lung mechanics and pulmonary function testing in cetaceans.

    PubMed

    Fahlman, Andreas; Loring, Stephen H; Levine, Gregg; Rocho-Levine, Julie; Austin, Trevor; Brodsky, Micah

    2015-07-01

    We measured esophageal pressures, respiratory flow rates, and expired O2 and CO2 in six adult bottlenose dolphins (Tursiops truncatus) during voluntary breaths and maximal (chuff) respiratory efforts. The data were used to estimate the dynamic specific lung compliance (sCL), the O2 consumption rate (V̇O2 ) and CO2 production rates (V̇CO2 ) during rest. Our results indicate that bottlenose dolphins have the capacity to generate respiratory flow rates that exceed 130 l s(-1) and 30 l s(-1) during expiration and inspiration, respectively. The esophageal pressures indicated that expiration is passive during voluntary breaths, but active during maximal efforts, whereas inspiration is active for all breaths. The average sCL of dolphins was 0.31±0.04 cmH2O(-1), which is considerably higher than that of humans (0.08 cmH2O(-1)) and that previously measured in a pilot whale (0.13 cmH2O(-1)). The average estimated V̇O2  and V̇CO2  using our breath-by-breath respirometry system ranged from 0.857 to 1.185 l O2 min(-1) and 0.589 to 0.851 l CO2 min(-1), respectively, which is similar to previously published metabolic measurements from the same animals using conventional flow-through respirometry. In addition, our custom-made system allows us to approximate end tidal gas composition. Our measurements provide novel data for respiratory physiology in cetaceans, which may be important for clinical medicine and conservation efforts.

  20. 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

  1. Assessment of the lung function status of the goldsmiths working in an unorganized sector of India

    PubMed Central

    Sahu, Subhashis; Roy, Biswajit; Moitra, Subhabrata

    2013-01-01

    Context: Exposure to various types of fumes and gases are very common in Jewelery industries. No Report is available regarding the effects of those fumes and gases on the respiratory functions of the goldsmiths. Due to lack of proper monitoring of the workplace environments in these unorganized sectors, workers get very much affected by the occupational exposures to those irritants. Aims: The present study aimed to investigate whether the occupational exposures to fumes and gases might alter the lung functions of the goldsmiths. Materials and Methods: A total of 118 goldsmiths and 66 unexposed control subjects were taken randomly for the study. The goldsmiths were further classified in 3 groups according to duration (year) of exposures in the work environment, ETA1 (less than 5 years), ETA2 (more than 5 years but less than 10 years), and ETA3 (more than 10 years). Peak expiratory flow rates (PEFR), forced vital capacity (FVC), and forced expiratory flow rates of different intervals (FEF25%, FEF50%, FEF75%, FEF25-75%) were measured using computerized Spirometer (Maestros Mediline, India). The statistical analyses were carried out using Minitab software version 3. Results: Lung functions of the goldsmiths significantly (P < 0.01) decreased from that of the control group. Inter-group comparison also showed the deteriorations of lung functions was associated with exposure time, and more exposed workers had significantly less (P < 0.01) efficiencies of lung functions. Conclusions: Workplace fumes and gases were responsible for deterioration of the lung function status of the goldsmiths. PMID:23661914

  2. 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

  3. 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

  4. 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.

  5. 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...

  6. 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.

  7. 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.

  8. 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

  9. 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...

  10. 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.

  11. Efficacy of pirfenidone in patients with idiopathic pulmonary fibrosis with more preserved lung function.

    PubMed

    Albera, Carlo; Costabel, Ulrich; Fagan, Elizabeth A; Glassberg, Marilyn K; Gorina, Eduard; Lancaster, Lisa; Lederer, David J; Nathan, Steven D; Spirig, Dominique; Swigris, Jeff J

    2016-09-01

    This post hoc analysis examined the differences in idiopathic pulmonary fibrosis disease progression and the effects of pirfenidone in patients stratified by more preserved versus less preserved baseline lung function status using forced vital capacity (FVC) or GAP (gender, age and physiology) index stage.Efficacy outcomes, i.e. FVC, 6-min walking distance (6MWD) and dyspnoea (University of California San Diego Shortness of Breath Questionnaire (UCSD SOBQ)), were analysed at 12 months in patients randomised to pirfenidone 2403 mg·day(-1) or placebo in the pooled phase 3 CAPACITY/ASCEND population (n=1247), with subgroups stratified by baseline FVC ≥80% versus <80% or GAP stage I versus II-III. Treatment-by-subgroup interaction was tested based on a rank ANCOVA model; factors in the model included study, region, treatment, subgroup and treatment-by-subgroup interaction term.Patients with both more preserved (FVC ≥80% or GAP stage I) and less preserved (FVC <80% or GAP stage II-III) lung function at baseline demonstrated clinically significant disease progression at 12 months in terms of categorical decline in FVC, 6MWD and UCSD SOBQ. The magnitude of pirfenidone treatment effect was comparable between subgroups, regardless of whether lung function was classified using FVC or GAP index stage.These findings support the initiation of treatment with pirfenidone, irrespective of stage of baseline lung function in this patient population. PMID:27471208

  12. 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...

  13. [A case of pulmonary tuberculosis with diminished lung function whose paradoxical reaction led to death].

    PubMed

    Omura, Harutaka; Kajiki, Akira; Nagata, Nobuhiko; Kitahara, Yoshinari; Wakamatsu, Kentarou; Minami, Takahiro; Taguchi, Kazuhito; Katahira, Katsuyuki

    2011-05-01

    Paradoxical reaction in tuberculosis treatment is not generally fatal. On rare occasion it can lead a patient with diminished lung function and poor general condition to death. A 60-year-old man with history of left upper lobe resection from tuberculosis was referred to our hospital due to the recurrence of tuberculosis. Sputum examination showed a positive smear with a Gaffky score of 10, and the chest X-ray and CT revealed pulmonary infiltrate with many cavities (bII2) on the whole left lung field. Anti-tuberculosis drugs (isoniazid, rifampicin, ethambutol and pyrazinamide) were administered, but his high fever persisted, and the infiltrate on the chest X-ray deteriorated. While the positive sputum smear persisted, the culture became negative after one month. The tuberculous bacilli were susceptible to all anti-tuberculosis drugs in vitro. Though we performed examinations and trial treatments for non-tuberculous conditions such as pneumonia and drug-induced pneumonia, the patient died after 6 months. A necropsy specimen taken from the worsening lesion (the right upper lobe) as shown on the chest X-ray revealed many epithelioid granulomas. The patient had malnutrition, diabetes, alcoholic hepatic disorder, and insanity. It is supposed that although antituberculosis drugs were effective, a large quantity of killed organisms was continuously excreted from many cavities in the left lung toward the right lung. Lesions in the right lung thus newly produced in this paradoxical reaction seemed to reduce the remaining lung function. In addition, poorly controlled diabetes caused deteriorated heart function. These multiple factors contributed to the poor prognosis of the patient and his ultimate death.

  14. Reliability of the Brazilian version of the Functional Assessment of Cancer Therapy‐Lung (FACT‐L) and the FACT‐Lung Symptom Index (FLSI)

    PubMed Central

    Juliana, Franceschini; Jardim, José R; Fernandes, Ana Luisa Godoy; Jamnik, Sérgio; Santoro, Ilka Lopes

    2010-01-01

    OBJECTIVES: The purpose of this study was to assess the reliability of the Brazilian version of the Functional Assessment of Cancer Therapy‐Lung (FACT‐L) with the FACT‐Lung Symptom Index (FLSI) questionnaire. INTRODUCTION: The assessment of quality of life in patients with lung cancer has become an important evaluative endpoint in current clinical trials. For lung cancer patients, one of the most common quality of life tools available is the FACT‐L. Despite the amount of data available regarding this questionnaire, there are no data on its performance in Brazilian lung cancer patients. METHODS: The FACT‐L with the FLSI questionnaire was prospectively administered to 30 consecutive, stable, lung cancer outpatients at baseline and at 2 weeks. RESULTS: The intraclass correlation coefficient between test and retest for the FACT‐L ranged from 0.79 to 0.96 and for the FLSI was 0.87. There was no correlation between these questionnaire dimensions and clinical or functional parameters. CONCLUSIONS: The Brazilian version of the FACT‐L with FLSI questionnaire is reliable and is quick and simple to apply. This instrument can now be used to properly evaluate the quality of life of Brazilian lung cancer patients. PMID:21340211

  15. 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

  16. 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…

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

    PubMed

    Liu, Yongjian; Ibricevic, 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 (Arg(9)), and labeled with imaging components to assess lung retention and cellular uptake after intratracheal administration. Radiolabeled microparticles (1-5 microm diameter) and nanoparticles (20-40 nm diameter) without and with Arg(9) 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 Arg(9) 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 Arg(9). Whereas microparticles may be advantageous for short-term applications, nanosized 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 Arg(9). 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.

  18. 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

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

    PubMed

    Liu, Yongjian; Ibricevic, 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 (Arg(9)), and labeled with imaging components to assess lung retention and cellular uptake after intratracheal administration. Radiolabeled microparticles (1-5 microm diameter) and nanoparticles (20-40 nm diameter) without and with Arg(9) 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 Arg(9) 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 Arg(9). Whereas microparticles may be advantageous for short-term applications, nanosized 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 Arg(9). 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

  20. 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

  1. Lung function growth and ambient ozone: a three-year population study in school children.

    PubMed

    Frischer, T; Studnicka, M; Gartner, C; Tauber, E; Horak, F; Veiter, A; Spengler, J; Kühr, J; Urbanek, R

    1999-08-01

    We followed a cohort of 1,150 children for 3 yr to investigate long-term effects of ambient ozone. Nine study sites were selected on the basis of air-quality data to represent a broad range of ozone exposure. In 1994, 1995, and 1996 lung function was recorded biannually, always before and after summertime. The effect of ozone was analyzed with regression analyses and study-site, a child's sex, atopy, passive smoking, baseline lung function, and increase in height were considered as confounding variables. A negative effect of summertime ozone on the pre- to post-summer-time change in FEV(1) (ml/d) was present in 1994 (beta = -0.019 ml/d/ppb; p < 0.01) and in 1995 (beta = -0.017 ml/d/ ppb; p < 0.05), but not in 1996 (beta = 0. 004 ml/d/ppb; p = 0.6); corresponding estimates for FVC were in 1994: beta = -0.022 ml/d/ppb, p < 0.005; 1995: beta = -0.018 ml/d/ppb, p < 0.05; and 1996: beta = 0.006 ml/d/ppb, p = 0.46. When all three study years were considered simultaneously, i.e., the changes in lung function between each of two subsequent surveys being the dependent variable, summertime ozone was associated with a lesser increase in FEV(1) (beta = -0.029 ml/d/ppb; p < 0.001), FVC (beta = -0.018 ml/d/ppb; p < 0.001), and MEF(50) (beta = -0.076 ml/s/d; p = 0.001). No consistent associations were observed for lung function and NO(2), SO(2) and PM(10). Long-term ambient ozone exposure might negatively influence lung function growth.

  2. 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

  3. Fourier-processed images of dynamic lung function from list-mode data

    SciTech Connect

    Zubal, I.G.; Rowe, R.W.; Bizais, Y.; Susskind, H.; Bennett, G.W.; Brill, A.B.

    1983-01-01

    Time and volume correlated amplitude and phase images are computed from nuclear medical ventilation studies and for dynamic transmission scans of the lungs. This is made possible by a hardware interface and data acquisition system, developed in-house, allowing camera events and multiple ancillary physiological signals (including lung volume) to be acquired simultaneously in list mode. The first harmonic amplitude and phase images are constructed on an event by event basis. These are computed for both equal time and equal lung volume increments. Time and volume correlated Fourier images for ventilation studies have shown details and functional structures not usually seen in conventional imaging techniques. Processed transmission scans show similar results compared to ventilation images.

  4. Lung function following very preterm birth in the era of 'new' bronchopulmonary dysplasia.

    PubMed

    Simpson, Shannon J; Hall, Graham L; Wilson, Andrew C

    2015-05-01

    One of the most significant complications of preterm birth is bronchopulmonary dysplasia (BPD). The pathophysiology of BPD has changed in recent years as advances in neonatal care have led to increased survival of smaller, more preterm, infants who display alterations to alveolar and pulmonary microvascular development. It is becoming clear that infants with 'new' BPD experience lung disease that persists into later childhood, however, the oldest of these children are just now entering young adulthood and therefore the longer term pulmonary implications remain unknown. The role of lung function testing in the identification and subsequent management of patients with lung disease resulting from a neonatal classification of BPD is reviewed based on the underlying pathophysiology of the disease.

  5. Junctional Adhesion Molecule A Promotes Epithelial Tight Junction Assembly to Augment Lung Barrier Function

    PubMed Central

    Mitchell, Leslie A.; Ward, Christina; Kwon, Mike; Mitchell, Patrick O.; Quintero, David A.; Nusrat, Asma; Parkos, Charles A.; Koval, Michael

    2016-01-01

    Epithelial barrier function is maintained by tight junction proteins that control paracellular fluid flux. Among these proteins is junctional adhesion molecule A (JAM-A), an Ig fold transmembrane protein. To assess JAM-A function in the lung, we depleted JAM-A in primary alveolar epithelial cells using shRNA. In cultured cells, loss of JAM-A caused an approximately 30% decrease in transepithelial resistance, decreased expression of the tight junction scaffold protein zonula occludens 1, and disrupted junctional localization of the structural transmembrane protein claudin-18. Consistent with findings in other organs, loss of JAM-A decreased β1 integrin expression and impaired filamentous actin formation. Using a model of mild systemic endoxotemia induced by i.p. injection of lipopolysaccharide, we report that JAM-A−/− mice showed increased susceptibility to pulmonary edema. On injury, the enhanced susceptibility of JAM-A−/− mice to edema correlated with increased, transient disruption of claudin-18, zonula occludens 1, and zonula occludens 2 localization to lung tight junctions in situ along with a delay in up-regulation of claudin-4. In contrast, wild-type mice showed no change in lung tight junction morphologic features in response to mild systemic endotoxemia. These findings support a key role of JAM-A in promoting tight junction homeostasis and lung barrier function by coordinating interactions among claudins, the tight junction scaffold, and the cytoskeleton. PMID:25438062

  6. 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.

  7. Characterizing Functional Lung Heterogeneity in COPD Using Reference Equations for CT Scan-Measured Lobar Volumes

    PubMed Central

    Diaz, Alejandro A.; Curran-Everett, Douglas; Muralidhar, Nivedita; Hersh, Craig P.; Zach, Jordan A.; Schroeder, Joyce; Lynch, David A.; Celli, Bartolome; Washko, George R.

    2013-01-01

    Background: CT scanning is increasingly used to characterize COPD. Although it is possible to obtain CT scan-measured lung lobe volumes, normal ranges remain unknown. Using COPDGene data, we developed reference equations for lobar volumes at maximal inflation (total lung capacity [TLC]) and relaxed exhalation (approximating functional residual capacity [FRC]). Methods: Linear regression was used to develop race-specific (non-Hispanic white [NHW], African American) reference equations for lobar volumes. Covariates included height and sex. Models were developed in a derivation cohort of 469 subjects with normal pulmonary function and validated in 546 similar subjects. These cohorts were combined to produce final prediction equations, which were applied to 2,191 subjects with old GOLD (Global Initiative for Chronic Obstructive Lung Disease) stage II to IV COPD. Results: In the derivation cohort, women had smaller lobar volumes than men. Height positively correlated with lobar volumes. Adjusting for height, NHWs had larger total lung and lobar volumes at TLC than African Americans; at FRC, NHWs only had larger lower lobes. Age and weight had no effect on lobar volumes at TLC but had small effects at FRC. In subjects with COPD at TLC, upper lobes exceeded 100% of predicted values in GOLD II disease; lower lobes were only inflated to this degree in subjects with GOLD IV disease. At FRC, gas trapping was severe irrespective of disease severity and appeared uniform across the lobes. Conclusions: Reference equations for lobar volumes may be useful in assessing regional lung dysfunction and how it changes in response to pharmacologic therapies and surgical or endoscopic lung volume reduction. PMID:23699785

  8. 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

  9. 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.

  10. Time course of lung function changes in atypical pneumonia.

    PubMed Central

    Benusiglio, L N; Stalder, H; Junod, A F

    1980-01-01

    We measured pulmonary function in each of 21 patients suffering from "atypical", non-bacterial pneumonia during the acute illness and during convalescence (two to 18 months) to study the course and the nature of functional impairment at different stages of the disease. In six patients, no aetiological agent was found. An aetiological agent was identified in 15 of the patients: Mycoplasma pneumoniae (seven patients), influenza A (three patients), parainfluenza 3 (one patient), varicella (two patients), Q fever (one patient), coxsackie B3 (one patient). At the time of admission we observed a restrictive pattern in 52%, an obstructive pattern (decreased FEV1/FVC ratio) in 52% abnormalities in distribution of ventilation (abnormal slope of phase 3) in 63%, and abnormalities in gas exchange (increased AaDO2) in 75% of the patients. The frequency of abnormalities in these pulmonary function tests decreased dramatically after two to four weeks and nearly disappeared in most patients during convalescence. The only major residual abnormality was a decreased FEV1/FVC ratio in five subjects, four of whom were smokers. However, when MMEF and V75 were measured at this stage, their average value for all the groups of patients with the exclusion of the Mycoplasma pneumoniae group, was markedly reduced. These data suggest that small airways involvement can be demonstrated during the convalescence of patients recovering from various types of atypical pneumonia other than those caused by Mycoplasma pneumoniae. PMID:7444825

  11. Interstitial pneumonia associated to peginterferon alpha-2a: A focus on lung function

    PubMed Central

    Cortés-Telles, Arturo

    2016-01-01

    Pulmonary toxicity related to the use of pegylated interferon alpha-2a during treatment of hepatitis C infections is rare; nonetheless, some cases with fatal outcomes have been reported. Evaluating patients’ pulmonary function is a key to diagnosis, follow-up and prognosis of several respiratory diseases, but case reports of respiratory manifestations related to the use of pegylated interferon alpha-2a have limited their findings to only baseline measurements. This paper examines the case of a 65-year-old woman with chronic hepatitis C virus infection who developed interstitial pneumonitis associated with pegylated interferon alpha-2a. Initial lung function evaluation revealed a marked reduction compared to an earlier assessment; the results were consistent with a moderate restricted pattern. Fortunately, over the ensuing 8 weeks of follow-up after discontinuing the drug, the patient recovered her lung function and experienced an overall improvement in her respiratory symptoms. PMID:27051119

  12. Perlite exposure and 4-year change in lung function.

    PubMed

    Polatli, M; Erdinç, M; Erdinç, E; Okyay, E

    2001-07-01

    Perlite is a volcanic glass or amorphous aluminium silicate composed of 71-75% SiO(2). When heated to 800-1100 degrees C, it expands to form processed perlite, which has a low density, high surface area, and a low thermal conductivity. The objective was to determine the effect of perlite exposure on pulmonary function tests. Pulmonary function tests in conjunction with chest radiogram were carried out in 36 perlite-exposed workers and 22 unexposed office workers in 1992 and 1996. Respirable dust level exceeded permissible dust levels in work places in the 4 years under study. Transfer coefficient (K(CO)) decline was significant in nonsmoker perlite-exposed workers (n=9), and found to be 5.28+/-0.71 (predicted 4.32+/-0.11) and 3.84+/-0.96 (predicted 4.18+/-0.18) 1/min/mmHg, in 1992 and 1996, respectively (P<0.001). Both smoker perlite workers and office workers showed significant obstruction to airflow in small airways with respect to predicted values and 4-year change in transfer factor (T(L), CO) was significant. Although predicted, 12-year perlite exposure did not lead to a decrease in mean pulmonary function test parameters, there was a tendency to a decline in T(L), CO in the 4-year study period, which may be due to high perlite dust levels. As early effects of perlite dust exposure may not be detected by spirometric measurements alone, the transfer coefficient should be added to spirometry.

  13. Inhaled Hydrogen Sulfide Improves Graft Function in an Experimental Model of Lung Transplantation

    PubMed Central

    George, Timothy J.; Arnaoutakis, George J.; Beaty, Claude A.; Jandu, Simran K.; Santhanam, Lakshmi; Berkowitz, Dan E.; Shah, Ashish S.

    2014-01-01

    Objectives: Ischemia-reperfusion(IRI) is a common complication of lung transplantation(LTx). Hydrogen sulfide(H2S) is a novel agent previously shown to slow metabolism and scavenge reactive oxygen species, potentially mitigating IRI. We hypothesized that pre-treatment with inhaled H2S would improve graft function in an ex vivo model of LTx. Methods: Rabbits(n=10) were ventilated for 2 hours prior to heart-lung bloc procurement. The treatment group(n=5) inhaled room air(21% O2) supplemented with 150 ppm H2S while the control group(n=5) inhaled room air alone. Both groups were gradually cooled to 34 C. All heart-lung blocs were then recovered and cold-stored in low potassium dextran solution for 18 hours. Following storage, the blocs were reperfused with donor rabbit blood in an ex vivo apparatus. Serial clinical parameters were assessed and serial tissue biochemistry was examined. Results: Prior to heart-lung bloc procurement, rabbits pre-treated with H2S exhibited similar oxygenation(p=0.1), ventilation(p=0.7), and heart rate(p=0.5); however, treated rabbits exhibited consistently higher mean arterial blood pressures(p=0.01). During reperfusion, lungs pre-treated with H2S had better oxygenation(p<0.01) and ventilation(p=0.02) as well as lower pulmonary artery pressures(p<0.01). Reactive oxygen species levels were lower in treated lungs during reperfusion(p=0.01). Additionally, prior to reperfusion, treated lungs demonstrated more preserved mitochondrial cytochrome c oxidase activity(p=0.01). Conclusions: To our knowledge, this study represents the first reported therapeutic use of inhaled H2S in an experimental model of LTx. After prolonged ischemia, lungs pre-treated with inhaled H2S exhibited improved graft function during reperfusion. Donor pre-treatment with inhaled H2S represents a potentially novel adjunct to conventional preservation techniques and merits further exploration. PMID:22771242

  14. [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.

  15. Obesity: systemic and pulmonary complications, biochemical abnormalities, and impairment of lung function.

    PubMed

    Mafort, Thiago Thomaz; Rufino, Rogério; Costa, Cláudia Henrique; Lopes, Agnaldo José

    2016-01-01

    Obesity is currently one of the major epidemics of this millennium and affects individuals throughout the world. It causes multiple systemic complications, some of which result in severe impairment of organs and tissues. These complications involve mechanical changes caused by the accumulation of adipose tissue and the numerous cytokines produced by adipocytes. Obesity also significantly interferes with respiratory function by decreasing lung volume, particularly the expiratory reserve volume and functional residual capacity. Because of the ineffectiveness of the respiratory muscles, strength and resistance may be reduced. All these factors lead to inspiratory overload, which increases respiratory effort, oxygen consumption, and respiratory energy expenditure. It is noteworthy that patterns of body fat distribution significantly influence the function of the respiratory system, likely via the direct mechanical effect of fat accumulation in the chest and abdominal regions. Weight loss caused by various types of treatment, including low-calorie diet, intragastric balloon, and bariatric surgery, significantly improves lung function and metabolic syndrome and reduces body mass index. Despite advances in the knowledge of pulmonary and systemic complications associated with obesity, longitudinal randomized studies are needed to assess the impact of weight loss on metabolic syndrome and lung function. PMID:27408717

  16. Altered Lung Function Test in Asymptomatic Women Using Biomass Fuel for Cooking

    PubMed Central

    2014-01-01

    Background: One third of the world’s population use biomass fuel like wood, dung or charcoal for cooking. The smoke from these organic materials increases the incidence of respiratory illness including chronic obstructive pulmonary disease and lung cancer. Aim: To evaluate forced expiratory lung volumes in asymptomatic women previously exposed to biomass fuel smoke. Materials and Methods: The study was done in 74 healthy asymptomatic women divided into two age matched groups of 37 each. Pulmonary function tests (PFT) were assessed by computerised spirometry and statistical comparisons done on women using biomass fuel (study group) and women using other sources of fuel (LPG/ electric stove) for cooking (control group). Results: The PFT results showed significant reduction in forced expiratory lung volumes like Forced Vital Capacity (FVC), Forced Expiratory Volume in 1st sec (FEV1), Forced Expiratory Flow between 25-75% (FEF 25-75%) and Forced Expiratory Volume percentage (FEV1%) in biomass fuel users as compared to those not exposed to biomass fuel smoke. Conclusion: The results of this study suggest that biomass fuel smoke may produce definite impairment in lung function, especially with regard to the smaller airways. PMID:25478331

  17. 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. PMID:26815503

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

    PubMed Central

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

    2009-01-01

    Summary 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. PMID:19181903

  19. Lung function in silica-exposed workers. A relationship to disease severity assessed by CT scan.

    PubMed

    Bégin, R; Ostiguy, G; Cantin, A; Bergeron, D

    1988-09-01

    To investigate the relationship of lung function, airflow limitation, and lung injury in silica-exposed workers, we analyzed the clinical, functional, and radiologic data of 94 long-term workers exposed in the granite industry or in foundries. The subjects were divided into four subsets based on chest roentgenogram and CT scan of the thorax: group 1 consisted of 21 subjects with category 0 chest roentgenogram and category 0 CT scan; group 2, 28 subjects with category E 1 on both chest roentgenogram and CT scan; group 3, 18 subjects with category E 1 on chest roentgenogram but with coalescence or conglomeration or both seen only on CT scan; and group 4, 27 subjects with category E 1 and coalescence or conglomeration or both on roentgenogram and CT scan. The groups did not differ in terms of age, height, cigarette smoking, or years of exposure. Lung volumes were significantly reduced only in group 4 (p less than 0.05). Lung compliance, diffusion capacity, and the rest-exercise P(A-a)O2 gradient were reduced in groups 3 and 4 (p less than 0.05). Expiratory flow rates were significantly reduced in groups 2, 3, and 4, with the lowest values in group 4. The expiratory flow rates in group 3 were significantly lower in group 3 than in group 2. These results support the concept that airflow in silica-exposed workers is significantly reduced when the disease is detectable on simple chest roentgenogram; coalescence or conglomeration or both on chest roentgenogram or CT scan is associated with significant loss of lung volumes, gas exchange function, and increased airflow obstruction.

  20. Ex Vivo Rehabilitation of Non-Heart-Beating Donor Lungs in a Preclinical Porcine Model: Delayed Perfusion Results in Superior Lung Function

    PubMed Central

    Mulloy, Daniel P.; Stone, Matthew L.; Crosby, Ivan K.; LaPar, Damien J.; Sharma, Ashish K.; Webb, David V.; Lau, Christine L.; Laubach, Victor E.; Kron, Irving L.

    2012-01-01

    Objectives Ex vivo lung perfusion (EVLP) is a promising modality for the evaluation and treatment of marginal donor lungs. The optimal timing of EVLP initiation and potential for rehabilitation of donor lungs with extended warm-ischemic times is unknown. This study compares the efficacy of different treatment strategies for uncontrolled non-heart-beating donor lungs. Methods Mature swine underwent hypoxic arrest followed by 60 minutes of no-touch warm-ischemia. Lungs were harvested and flushed with 4°C Perfadex®. Three groups (n=5/group) were stratified according to preservation method: cold-static preservation (CSP: 4 hrs 4°C storage), immediate EVLP (I-EVLP: 4 hrs EVLP at 37°C), and delayed EVLP (D-EVLP: 4 hrs cold storage followed by 4 hrs EVLP). EVLP groups were perfused with Steen solution™ supplemented with heparin, methylprednisolone, cefazolin, and an adenosine 2A receptor agonist. Lungs then underwent allotransplantation and four hours of recipient reperfusion prior to allograft assessment for resultant ischemia-reperfusion injury. Results Donor blood oxygenation (PO2:FiO2) prior to euthanasia was not different between groups. Oxygenation after transplantation was significantly higher in the D-EVLP group compared to the I-EVLP or CSP groups. Mean airway pressure, pulmonary artery pressure, and expression of IL-8, IL-1β, and TNF-α were all significantly reduced in the D-EVLP group. Importantly, post-transplant oxygenation exceeded acceptable clinical levels only in D-EVLP lungs. Conclusions Uncontrolled non-heart-beating donor lungs with extended warm-ischemia can be reconditioned for successful transplantation. The combination of CSP and EVLP present in the D-EVLP group was necessary to obtain optimal post-transplant function. This finding, if confirmed clinically, will allow expanded use of non-heart-beating donor lungs. PMID:22944084

  1. Individualized lung function trends in alpha-1-antitrypsin deficiency: a need for patience in order to provide patient centered management?

    PubMed Central

    Stockley, Robert A; Edgar, Ross G; Pillai, Anilkumar; Turner, Alice M

    2016-01-01

    Background Chronic obstructive pulmonary disease (COPD) is characterized by fixed airflow obstruction and accelerated decline of forced expired volume in 1 second (FEV1). Alpha-1-antitrypsin deficiency is a genetic cause of COPD and associated with more rapid decline in lung function, even in some never smokers (NS) but the potential for individualized assessment to reveal differences when compared to group analyses has rarely been considered. Methods We analyzed decline in post-bronchodilator FEV1 and gas transfer (% predicted) over at least 3 years (mean= 6.11, 95% CI 5.80–6.41) in our unique data set of 482 patients with alpha-1-antitrypsin deficiency (PiZ) to determine individual rates of decline, implications for prognosis, and potential clinical management. Findings There was a marked variation in individual rates of FEV1 decline from levels consistent with normal aging (observed in 23.5% of patients with established COPD, 57.5% of those without) to those of rapidly declining COPD. Gas transfer did not decline in 12.8% of NS and 20.7% of ex-smokers with established COPD (33.3% and 25.0%, respectively, for those without COPD). There was no correlation between decline in gas transfer and FEV1 for those with COPD, although a weak relationship existed for those without (r=0.218; P<0.025). Conclusion These data confirm differing individual rates of lung function decline in alpha-1-antitrypsin deficiency, indicating the importance of comprehensive physiological assessment and a personalized approach to patient management. PMID:27536086

  2. 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.

  3. Dietary intake, lung function and airway inflammation in Mexico City school children exposed to air pollutants

    PubMed Central

    2009-01-01

    Introduction Air pollutant exposure has been associated with an increase in inflammatory markers and a decline in lung function in asthmatic children. Several studies suggest that dietary intake of fruits and vegetables might modify the adverse effect of air pollutants. Methods A total of 158 asthmatic children recruited at the Children's Hospital of Mexico and 50 non-asthmatic children were followed for 22 weeks. Pulmonary function was measured and nasal lavage collected and analyzed every 2 weeks. Dietary intake was evaluated using a 108-item food frequency questionnaire and a fruit and vegetable index (FVI) and a Mediterranean diet index (MDI) were constructed. The impact of these indices on lung function and interleukin-8 (IL-8) and their interaction with air pollutants were determined using mixed regression models with random intercept and random slope. Results FVI was inversely related to IL-8 levels in nasal lavage (p < 0.02) with a significant inverse trend (test for trend p < 0.001), MDI was positively related to lung function (p < 0.05), and children in the highest category of MDI had a higher FEV1 (test for trend p < 0.12) and FVC (test for trend p < 0.06) than children in the lowest category. A significant interaction was observed between FVI and ozone for FEV1 and FVC as was with MDI and ozone for FVC. No effect of diet was observed among healthy children. Conclusion Our results suggest that fruit and vegetable intake and close adherence to the Mediterranean diet have a beneficial effect on inflammatory response and lung function in asthmatic children living in Mexico City. PMID:20003306

  4. 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

  5. Reduction in lung functions in type-2 diabetes in Indian population: correlation with glycemic status.

    PubMed

    Dharwadkar, Anand R; Dharwadkar, Asha A; Banu, Gouher; Bagali, Shrilaxmi

    2011-01-01

    The purpose of this study was to evaluate pulmonary functions in patients with Type-2 diabetes mellitus and to determine their correlation with glycemic status of diabetes in Indian population. Forty Type-2 diabetic patients, aged 30-60 years, with diabetic duration of 1-20 years, were included in the study. FVC, FEV1, & FEV1% are recorded by Benedict's Roth spirometer. PEFR and MEP were recorded by Wright's Peak flow meter & Modified Black's apparatus. Glycemic status of subjects was determined by FBS & PPBS by Glucose oxidase & peroxidase methods. And results were analyzed by calculating Mean +/- SD, using Student's t test, and Pearson correlation. All the respiratory parameters are reduced in Type-2 diabetic patients compared to control of which FEV1, FEV1%, & MEP show very highly significant reduction (P=0.000). Lung functions are negatively correlated with glycemic status & duration of diabetes. (r = -0.390, & -0.342) Reduction in dynamic lung functions and its negative correlation to glycemic status might be due to respiratory muscle weakness as indicated by highly significant reduction in MEP. Hence strict glycemic control and breathing exercises to strengthen the respiratory muscles may improve lung function in diabetics. PMID:22319899

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

    PubMed

    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.

  7. Salivary Telomere Length and Lung Function in Adolescents Born Very Preterm: A Prospective Multicenter Study

    PubMed Central

    Hadchouel, Alice; Marchand-Martin, Laetitia; Franco-Montoya, Marie-Laure; Peaudecerf, Laetitia; Ancel, Pierre-Yves; Delacourt, Christophe

    2015-01-01

    Preterm birth is associated with abnormal respiratory functions throughout life. The mechanisms underlying these long-term consequences are still unclear. Shortening of telomeres was associated with many conditions, such as chronic obstructive pulmonary disease. We aimed to search for an association between telomere length and lung function in adolescents born preterm. Lung function and telomere length were measured in 236 adolescents born preterm and 38 born full-term from the longitudinal EPIPAGE cohort. Associations between telomere length and spirometric indices were tested in univariate and multivariate models accounting for confounding factors in the study population. Airflows were significantly lower in adolescents born preterm than controls; forced expiratory volume in one second was 12% lower in the extremely preterm born group than controls (p<0.001). Lower birth weight, bronchopulmonary dysplasia and postnatal sepsis were significantly associated with lower airflow values. Gender was the only factor that was significantly associated with telomere length. Telomere length correlated with forced expiratory flow 25–75 in the extremely preterm adolescent group in univariate and multivariate analyses (p = 0.01 and p = 0.02, respectively). We evidenced an association between telomere length and abnormal airflow in a population of adolescents born extremely preterm. There was no evident association with perinatal events. This suggests other involved factors, such as a continuing airway oxidative stress leading to persistent inflammation and altered lung function, ultimately increasing susceptibility to chronic obstructive pulmonary disease. PMID:26355460

  8. 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.

  9. Impact of backpack type on respiratory muscle strength and lung function in children.

    PubMed

    Vieira, Ana Christina; Ribeiro, Fernando

    2015-01-01

    We examine the influence of backpack type on lung function and respiratory muscle strength in children. Thirty-seven children were assessed for lung function and inspiratory and expiratory muscle strength under four randomly determined conditions: unloaded erect standing and three conditions carrying 15% of the child's body weight. In these three conditions, children carried the weight on a backpack with bilateral shoulder straps carried over both shoulders, on a backpack with bilateral shoulder straps carried over one shoulder and on a backpack with a mono shoulder strap. Significantly lower forced vital capacity, forced expiratory volume in one second and maximal expiratory pressure were observed when children carried a backpack with a mono shoulder strap compared to the unloaded standing position. In conclusion, the restrictive effect and the decrease in expiratory muscle strength were more pronounced for the backpack with a mono shoulder strap, suggesting that a double strap backpack is preferable to a mono shoulder strap backpack. Practitioner summary: There is little known about the effect of schoolbags on respiratory muscle function. We investigated the influence of backpack type on lung function and respiratory muscle strength. A backpack with a mono shoulder strap created a restrictive effect and a decrease in strength, suggesting that a double strap backpack is preferable to a mono shoulder strap backpack. PMID:25584722

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

    PubMed

    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. PMID:6830030

  11. 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

  12. 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

  13. Genome-wide association study identifies TH1 pathway genes associated with lung function in asthmatic patients

    PubMed Central

    Li, Xingnan; Hawkins, Gregory A.; Ampleford, Elizabeth J.; Moore, Wendy C.; Li, Huashi; Hastie, Annette T.; Howard, Timothy D.; Boushey, Homer A.; Busse, William W.; Calhoun, William J.; Castro, Mario; Erzurum, Serpil C.; Israel, Elliot; Lemanske, Robert F.; Szefler, Stanley J.; Wasserman, Stephen I.; Wenzel, Sally E.; Peters, Stephen P.; Meyers, Deborah A.; Bleecker, Eugene R.

    2013-01-01

    Background Recent meta-analyses of genome-wide association studies in general populations of European descent have identified 28 loci for lung function. Objective We sought to identify novel lung function loci specifically for asthma and to confirm lung function loci identified in general populations. Methods Genome-wide association studies of lung function (percent predicted FEV1 [ppFEV1], percent predicted forced vital capacity, and FEV1/forced vital capacity ratio) were performed in 4 white populations of European descent (n = 1544), followed by meta-analyses. Results Seven of 28 previously identified lung function loci (HHIP, FAM13A, THSD4, GSTCD, NOTCH4-AGER, RARB, and ZNF323) identified in general populations were confirmed at single nucleotide polymorphism (SNP) levels (P < .05). Four of 32 loci (IL12A, IL12RB1, STAT4, and IRF2) associated with ppFEV1 (P < 10−4) belong to the TH1 or IL-12 cytokine family pathway. By using a linear additive model, these 4 TH1 pathway SNPs cumulatively explained 2.9% to 7.8% of the variance in ppFEV1 values in 4 populations (P = 3 × 10−11). Genetic scores of these 4 SNPs were associated with ppFEV1 values (P = 2 × 10−7) and the American Thoracic Society severe asthma classification (P = .005) in the Severe Asthma Research Program population. TH2 pathway genes (IL13, TSLP, IL33, and IL1RL1) conferring asthma susceptibility were not associated with lung function. Conclusion Genes involved in airway structure/remodeling are associated with lung function in both general populations and asthmatic subjects. TH1 pathway genes involved in anti-virus/bacterial infection and inflammation modify lung function in asthmatic subjects. Genes associated with lung function that might affect asthma severity are distinct from those genes associated with asthma susceptibility. PMID:23541324

  14. [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.

  15. 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. PMID:26306104

  16. Acute lung function responses to ambient acid aerosol exposures in children

    SciTech Connect

    Raizenne, M.E.; Burnett, R.T.; Stern, B.; Franklin, C.A.; Spengler, J.D.

    1989-02-01

    We examined the relationship between lung function changes and ambient acid aerosol episodes in children attending a residential summer camp. Young females (112) performed daily spirometry, and 96 were assessed on one occasion for airway hyperresponsiveness using a methacholine bronchoprovocation test. Air quality measurements were performed on site and four distinct acid aerosol episodes were observed during the 41-day study. The maximum values observed during the 41-day study were: O/sub 3/ at 143 ppb; H/sub 2/SO/sub 4/ at 47.7 micrograms/m/sup 3/; and (H+) at 550 nmole/m/sup 3/. Maximum decrements of 3.5 and 7% for FEV1 and PEF, respectively, were observed to be associated with the air pollution episodes. There was some evidence of a differential lung function response to the episodes where children with a positive response to a methacholine challenge had larger decrements compared to their nonresponsive counterparts.

  17. [Lung function and carboxyhemoglobin during the smog episode of January 1987].

    PubMed

    Wichmann, H E; Sugiri, D; Islam, M S; Haake, D; Roscovanu, A

    1988-11-01

    During a phase of elevated ambient air pollution in January 1987 the alert level of the smog alarm recommendation in Northrhine Westfalia (FRG) was reached. The average concentrations during examinations were 0.255 mg/m3 SO2 and 3.2 mg/m3 CO at the closest station. In 111 healthy persons in Cologne and Düsseldorf, resistance measured by oscillatory method was elevated during this period compared to control examinations. In 59 patients with moderate airway-obstruction from different parts of West Germany lung function showed further deterioration during the smog phase: Airway resistance measured by body-plethysmography was higher than during a control period, FVC, FEV1, PEF and MEF75 were decreased. Finally levels of carboxyhemoglobin in blood also were increased in 46 healthy nonsmokers. The investigation shows, that even in moderate smog episodes (compared to earlier years) small, but consistent changes of lung function parameter can be measured.

  18. Acute lung function responses to ambient acid aerosol exposures in children.

    PubMed

    Raizenne, M E; Burnett, R T; Stern, B; Franklin, C A; Spengler, J D

    1989-02-01

    We examined the relationship between lung function changes and ambient acid aerosol episodes in children attending a residential summer camp. Young females (112) performed daily spirometry, and 96 were assessed on one occasion for airway hyperresponsiveness using a methacholine bronchoprovocation test. Air quality measurements were performed on site and four distinct acid aerosol episodes were observed during the 41-day study. The maximum values observed during the 41-day study were: O3 at 143 ppb; H2SO4 at 47.7 micrograms/m3; and [H+] at 550 nmole/m3. Maximum decrements of 3.5 and 7% for FEV1 and PEF, respectively, were observed to be associated with the air pollution episodes. There was some evidence of a differential lung function response to the episodes where children with a positive response to a methacholine challenge had larger decrements compared to their nonresponsive counterparts.

  19. 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.

  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. 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

  2. Longer telomere length in COPD patients with α1-antitrypsin deficiency independent of lung function.

    PubMed

    Saferali, Aabida; Lee, Jee; Sin, Don D; Rouhani, Farshid N; Brantly, Mark L; Sandford, Andrew J

    2014-01-01

    Oxidative stress is involved in the pathogenesis of airway obstruction in α1-antitrypsin deficient patients. This may result in a shortening of telomere length, resulting in cellular senescence. To test whether telomere length differs in α1-antitrypsin deficient patients compared with controls, we measured telomere length in DNA from peripheral blood cells of 217 α1-antitrypsin deficient patients and 217 control COPD patients. We also tested for differences in telomere length between DNA from blood and DNA from lung tissue in a subset of 51 controls. We found that telomere length in the blood was significantly longer in α1-antitrypsin deficient COPD patients compared with control COPD patients (p = 1×10(-29)). Telomere length was not related to lung function in α1-antitrypsin deficient patients (p = 0.3122) or in COPD controls (p = 0.1430). Although mean telomere length was significantly shorter in the blood when compared with the lungs (p = 0.0078), telomere length was correlated between the two tissue types (p = 0.0122). Our results indicate that telomere length is better preserved in α1-antitrypsin deficient COPD patients than in non-deficient patients. In addition, measurement of telomere length in the blood may be a suitable surrogate for measurement in the lung.

  3. Role of TNFR1 in lung injury and altered lung function induced by the model sulfur mustard vesicant, 2-chloroethyl ethyl sulfide

    SciTech Connect

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

    2011-02-01

    Lung toxicity induced by sulfur mustard is associated with inflammation and oxidative stress. To elucidate mechanisms mediating pulmonary damage, we used 2-chloroethyl ethyl sulfide (CEES), a model sulfur mustard vesicant. Male mice (B6129) were treated intratracheally with CEES (3 or 6 mg/kg) or control. Animals were sacrificed 3, 7 or 14 days later and bronchoalveolar lavage (BAL) fluid and lung tissue collected. Treatment of mice with CEES resulted in an increase in BAL protein, an indication of alveolar epithelial damage, within 3 days. Expression of Ym1, an oxidative stress marker also increased in the lung, along with inducible nitric oxide synthase, and at 14 days, cyclooxygenase-2 and monocyte chemotactic protein-1, inflammatory proteins implicated in tissue injury. These responses were attenuated in mice lacking the p55 receptor for TNF{alpha} (TNFR1-/-), demonstrating that signaling via TNFR1 is key to CEES-induced injury, oxidative stress, and inflammation. CEES-induced upregulation of CuZn-superoxide dismutase (SOD) and MnSOD was delayed or absent in TNFR1-/- mice, relative to WT mice, suggesting that TNF{alpha} mediates early antioxidant responses to lung toxicants. Treatment of WT mice with CEES also resulted in functional alterations in the lung including decreases in compliance and increases in elastance. Additionally, methacholine-induced alterations in total lung resistance and central airway resistance were dampened by CEES. Loss of TNFR1 resulted in blunted functional responses to CEES. These effects were most notable in the airways. These data suggest that targeting TNF{alpha} signaling may be useful in mitigating lung injury, inflammation and functional alterations induced by vesicants.

  4. 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

  5. Welding, longitudinal lung function decline and chronic respiratory symptoms: a systematic review of cohort studies.

    PubMed

    Szram, Joanna; Schofield, Susie J; Cosgrove, Martin P; Cullinan, Paul

    2013-11-01

    While the acute respiratory risks of welding are well characterised, more chronic effects, including those on lung function, are less clear. We carried out a systematic review of published longitudinal studies of lung function decline in welders. Original cohort studies documenting two or more sequential measurements of lung function were reviewed. Meta-analysis was carried out on studies with suitable data on forced expiratory volume in 1 s (FEV1). Seven studies were included; their quality (measured on the Newcastle-Ottawa scale) was good, although exposure assessment was limited and the studies showed significant heterogeneity. Five had data suitable for meta-analysis; the pooled estimate of the difference in FEV1 decline between welders and nonwelders was -9.0 mL · year(-1) (95% CI -22.5-4.5; p=0.193). The pooled estimates of difference in annual FEV1 decline between welders and referents who smoked was -13.7 mL · year(-1) (95% CI -33.6-6.3; p=0.179). For welders and referents who did not smoke the estimated difference was -3.8 mL · year(-1) (95% CI -20.2-12.6; p=0.650). Symptom prevalence data were mainly narrative; smoking appeared to have the greatest effect on symptom evolution. Collectively, available longitudinal data on decline of lung function in welders and respiratory symptoms suggest a greater effect in those who smoke, supporting a focus on smoking cessation as well as control of fume exposure in this trade. Further prospective studies are required to confirm these findings.

  6. Asthma, respiratory symptoms and lung function in children living near a petrochemical site.

    PubMed

    Rovira, Enric; Cuadras, Anna; Aguilar, Xavier; Esteban, Leonardo; Borràs-Santos, Alícia; Zock, Jan-Paul; Sunyer, Jordi

    2014-08-01

    Residential proximity to environmental hazards has been related to adverse health outcomes. Respiratory health and allergies in children living near petrochemical sites have not been extensively studied. We evaluated the association between residential proximity to the petrochemical site of Tarragona (Catalonia, Spain) and the prevalence of asthma, respiratory symptoms and lung function in children. Children aged 6-7 (n=2672) and adolescents aged 13-14 (n=2524) residing near two large petrochemical sites and those living in a city with medium vehicular traffic were cross-sectionally compared with children from an area with low vehicular traffic and without industry. The prevalence of symptoms was measured using the International Study of Asthma and Allergies in Childhood written and video questionnaires. Lung function measurements were done in a subsample of 959 adolescents in the four areas. Multivariable analyses were done to estimate the effects of the residential area on symptoms and lung function adjusted for potential confounders. Crude prevalence of symptoms was similar across the studied areas. After adjustment, children and adolescents living near a petrochemical site had a statistically significant higher prevalence of respiratory hospitalizations in the previous year (Prevalence Ratio (PR)=1.49; 95%CI, 1.06-2.09) and of nocturnal cough (PR=1.29; 95%CI 1.05-1.57), respectively. Reduced lung function values among adolescents residing near the petrochemical areas were not observed. Although a higher prevalence of asthma in children and adolescents living near the petrochemical sites could not be demonstrated, as described in other studies, respiratory hospitalizations and nocturnal cough could be related to short-term exposures to pollutants. Other clinical and sub-clinical respiratory health effects in the petrochemical industry areas should be investigated.

  7. Hardware accelerator of convolution with exponential function for image processing applications

    NASA Astrophysics Data System (ADS)

    Panchenko, Ivan; Bucha, Victor

    2015-12-01

    In this paper we describe a Hardware Accelerator (HWA) for fast recursive approximation of separable convolution with exponential function. This filter can be used in many Image Processing (IP) applications, e.g. depth-dependent image blur, image enhancement and disparity estimation. We have adopted this filter RTL implementation to provide maximum throughput in constrains of required memory bandwidth and hardware resources to provide a power-efficient VLSI implementation.

  8. Lung function in patients with gastro-esophageal reflux disease and respiratory symptoms.

    PubMed

    Pirogowicz, I; Patyk, M; Popecki, P; Rudnicki, J; Gojny, L; Pokorski, Mieczyslaw

    2013-01-01

    The aim of this study was to investigate lung function in patients with gastro-esophageal reflux disease (GERD) who present respiratory symptoms suggestive of the possibility of co-morbid asthma. The study encompassed 20 patients (9 women and 11 men; age range from 11 to 68 years) diagnosed with GERD and presenting with chronic cough and other non-specific periodic respiratory complaints. The control group consisted of closely gender and age-matched 20 subjects without any gastrointestinal or respiratory symptoms. All patients and control subjects were tested for lung function, which encompassed spirometric and flow-volume variables. We found that none of the GERD patients had lung function abnormalities characteristic of asthma. There were, however, decreases in forced expired volume in 1 s, forced vital capacity, and in maximal instantaneous forced expiratory flows in the GERD patients compared with the healthy subjects. We conclude that cough accompanying GERD is unlikely to be associated with the presence of co-morbid asthma, but rather suggests a mild airway inflammation developing as a sequel of GERD. The corollary is that chronic cough should prompt physician's attention to consider diagnostic work-up toward the possibility of GERD. PMID:23835974

  9. The Axl receptor tyrosine kinase is a discriminator of macrophage function in the inflamed lung

    PubMed Central

    Kaur, Manminder; Bell, Thomas J; Fujino, Naoya; Cook, Peter C; Svedberg, Freya R; MacDonald, Andrew S; Maciewicz, Rose A; Singh, Dave; Hussell, Tracy

    2014-01-01

    Much of the biology surrounding macrophage functional specificity has arisen through examining inflammation-induced polarising signals, but this also occurs in homeostasis, requiring tissue-specific environmental triggers that influence macrophage phenotype and function. The TAM receptor family of receptor tyrosine kinases (Tyro3, Axl and MerTK) mediates the non-inflammatory removal of apoptotic cells by phagocytes through the bridging phosphatidylserine-binding molecules Gas6 or Protein S. We show that one such TAM receptor (Axl) is exclusively expressed on mouse airway macrophages, but not interstitial macrophages and other lung leukocytes, under homeostatic conditions and is constitutively ligated to Gas6. Axl expression is potently induced by GM-CSF expressed in the healthy and inflamed airway, and by type I interferon or TLR3 stimulation on human and mouse macrophages, indicating potential involvement of Axl in apoptotic cell removal under inflammatory conditions. Indeed, an absence of Axl does not cause sterile inflammation in health, but leads to exaggerated lung inflammatory disease upon influenza infection. These data imply that Axl allows specific identification of airway macrophages, and that its expression is critical for macrophage functional compartmentalisation in the airspaces or lung interstitium. We propose that this may be a critical feature to prevent excessive inflammation due to secondary necrosis of apoptotic cells that have not been cleared by efferocytosis. PMID:25603826

  10. 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

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

    PubMed

    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.

  12. 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.

  13. Respiratory symptoms and lung function in jute processing workers: a primary investigation.

    PubMed

    Zhou, C; Liu, Z L; Ho, C S; Lou, J Z

    1989-01-01

    This paper presents the results of an investigation of respiratory symptoms and lung function of 404 workers who had been exposed to jute dust in a jute mill. Measurement of total dust concentration and analysis of dust composition were also conducted. Most workers in the jute mill were exposed to jute dusts containing less than 5% silica, whereas a few workers were exposed to dusts containing approximately 10-15% silica. Male smokers and nonsmokers in the dust-exposed group had a higher prevalence of cough and chest tightness compared with those in the control group. Among dust-exposed workers, female nonsmokers had a significantly higher prevalence of cough, chronic bronchitis, chest tightness, and dyspnea than those in the control group. Lung function tests showed that dust-exposed workers had a greater incidence of abnormal lung function than did control workers, as measured by percentage of predicted forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1.0), and FEV1.0/FVC. Dust exposure was the main cause of respiratory symptoms and abnormal values of FEV1.0, but both cigarette smoking and dust exposure contributed to the abnormal values reported for FEV1.0.

  14. 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

  15. Frequent loss of Fas expression and function in human lung tumours with overexpression of FasL in small cell lung carcinoma.

    PubMed

    Viard-Leveugle, Isabelle; Veyrenc, Sylvie; French, Lars E; Brambilla, Christian; Brambilla, Elisabeth

    2003-10-01

    Fas (CD95) and its ligand FasL signal apoptosis and are involved in tissue homeostasis and the elimination of target cells by cytotoxic T cells. Corruption of this signalling pathway in tumour cells, for example by reduced Fas expression or increased FasL expression, can participate in tumour development and immune escape. The present study has analysed Fas/FasL expression and Fas death signalling function in vivo in lung tumour tissues [57 non-small cell lung carcinomas and 64 neuroendocrine lung tumours including small cell lung carcinoma (SCLC)] in comparison with normal lung tissue, and in vitro in neuroendocrine tumour cell lines in comparison with normal human bronchial epithelial cells. The Fas expression score was markedly decreased compared with normal lung tissue in 90% of the 121 lung tumours and was completely lost in 24%. The Fas staining pattern suggested cytoplasmic Fas expression in tumours, whereas membrane expression was observed in normal lung tissue. Loss of Fas at the cell surface was also shown in vitro by FACS analysis of neuroendocrine tumour cell lines and was concomitant with the resistance of tumour cells to FasL-mediated apoptosis according to in vitro cell viability. The lack of cell surface Fas expression in tumour cell lines resulted from the lack of intracellular Fas protein due to impaired Fas gene transcription. The FasL expression score was also decreased in most non-small cell lung carcinomas compared with normal bronchial cells, whereas 91% of SCLCs had higher expression than normal cells. FasL overexpression was related to advanced tumour stage as well as to a Fas/FasL ratio less than 1. It is concluded that a marked decrease in Fas expression may be part of lung tumourigenesis allowing tumour cells to escape from apoptosis. FasL overexpression in the context of Fas down-regulation in SCLC predicts the ability of SCLC cells to induce paracrine killing of Fas-expressing cytotoxic T cells. In lung tumours, Fas restoration may

  16. 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.

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

    PubMed

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

    2016-03-01

    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.

  18. 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

  19. 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.

  20. Arsenic Exposure and Impaired Lung Function. Findings from a Large Population-based Prospective Cohort Study

    PubMed Central

    Parvez, Faruque; Chen, Yu; Yunus, Mahbub; Olopade, Christopher; Segers, Stephanie; Slavkovich, Vesna; Argos, Maria; Hasan, Rabiul; Ahmed, Alauddin; Islam, Tariqul; Akter, Mahmud M.; Graziano, Joseph H.

    2013-01-01

    Rationale: Exposure to arsenic through drinking water has been linked to respiratory symptoms, obstructive lung diseases, and mortality from respiratory diseases. Limited evidence for the deleterious effects on lung function exists among individuals exposed to a high dose of arsenic. Objectives: To determine the deleterious effects on lung function that exist among individuals exposed to a high dose of arsenic. Methods: In 950 individuals who presented with any respiratory symptom among a population-based cohort of 20,033 adults, we evaluated the association between arsenic exposure, measured by well water and urinary arsenic concentrations measured at baseline, and post-bronchodilator–administered pulmonary function assessed during follow-up. Measurements and Main Results: For every one SD increase in baseline water arsenic exposure, we observed a lower level of FEV1 (−46.5 ml; P < 0.0005) and FVC (−53.1 ml; P < 0.01) in regression models adjusted for age, sex, body mass index, smoking, socioeconomic status, betel nut use, and arsenical skin lesions status. Similar inverse relationships were observed between baseline urinary arsenic and FEV1 (−48.3 ml; P < 0.005) and FVC (−55.2 ml; P < 0.01) in adjusted models. Our analyses also demonstrated a dose-related decrease in lung function with increasing levels of baseline water and urinary arsenic. This association remained significant in never-smokers and individuals without skin lesions, and was stronger in male smokers. Among male smokers and individuals with skin lesions, every one SD increase in water arsenic was related to a significant reduction of FEV1 (−74.4 ml, P < 0.01; and −116.1 ml, P < 0.05) and FVC (−72.8 ml, P = 0.02; and −146.9 ml, P = 0.004), respectively. Conclusions: This large population-based study confirms that arsenic exposure is associated with impaired lung function and the deleterious effect is evident at low- to moderate-dose range. PMID:23848239

  1. 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

  2. Association of ambient air quality with children`s lung function in urban and rural Iran

    SciTech Connect

    Asgari, M.M.; Dubois, A.; Beckett, W.S.; Asgari, M.; Gent, J.

    1998-05-01

    During the summer of 1994, a cross-sectional epidemiological study, in which the pulmonary function of children in Tehran was compared with pulmonary function in children in a rural town in Iran, was conducted. Four hundred children aged 5--11 y were studied. Daytime ambient nitrogen dioxide, sulfur dioxide, and particulate matter were measured with portable devices, which were placed in the children`s neighborhoods on the days of study. Levels of these ambient substances were markedly higher in urban Tehran than in rural areas. Children`s parents were questioned about home environmental exposures (including heating source and environmental tobacco smoke) and the children`s respiratory symptoms. Pulmonary function was assessed, both by spirometry and peak expiratory flow meter. Forced expiratory volume in 1 s and forced vital capacity--as a percentage of predicted for age, sex and height--were significantly lower in urban children than in rural children. Both measurements evidenced significant reverse correlations with levels of sulfur dioxide, nitrogen dioxide, and particulate matter. Differences in spirometric lung function were not explained by nutritional status, as assessed by height and weight for age, or by home environmental exposures. Reported airway symptoms were higher among rural children, whereas reported physician diagnosis of bronchitis and asthma were higher among urban children. The association between higher pollutant concentrations and reduced pulmonary function in this urban-rural comparison suggests that there is an effect of urban air pollution on short-term lung function and/or lung growth and development during the preadolescent years.

  3. Distribution of computer functionality for accelerator control at the Brookhaven AGS

    SciTech Connect

    Stevens, A.; Clifford, T.; Frankel, R.

    1985-01-01

    A set of physical and functional system components and their interconnection protocols have been established for all controls work at the AGS. Portions of these designs were tested as part of enhanced operation of the AGS as a source of polarized protons and additional segments will be implemented during the continuing construction efforts which are adding heavy ion capability to our facility. Included in our efforts are the following computer and control system elements: a broad band local area network, which embodies MODEMS; transmission systems and branch interface units; a hierarchical layer, which performs certain data base and watchdog/alarm functions; a group of work station processors (Apollo's) which perform the function of traditional minicomputer host(s) and a layer, which provides both real time control and standardization functions for accelerator devices and instrumentation. Data base and other accelerator functionality is assigned to the most correct level within our network for both real time performance, long-term utility, and orderly growth.

  4. 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.

  5. Influence of psychological intervention on pain and immune functions of patients receiving lung cancer surgery

    PubMed Central

    Zhao, Xinying; Cui, Limin; Wang, Wei; Su, Quanzhi; Li, Xiuzhi; Wu, Junben

    2016-01-01

    Objective: To observe the influence of psychological intervention on pain, immune system and adrenocortical functions of patients receiving lung cancer surgery. Methods: We selected 124 patients who received surgery for treating stage I or II lung cancer and divided into experimental group and control group. The experimental group received comprehensive psychological intervention while the control group was given conventional nursing intervention. Pain of patients in two groups was evaluated by visual analog scale (VAS). Before and after intervention, CD3+, CD4+, CD8+, CD4+/CD8+ and free cortisol level in serum were measured. Moreover, QLQ-C30, a life quality measurement scale developed by European Organization for Research and Treatment of Cancer (EORTC) was used. Results: Compared to control group, VAS of patients in experimental group remarkably decreased before anesthesia, 6 hour, 12 hour 24 hour and 48 hour after surgery (P<0.05), and moreover, OLQ-C30 score and various factor scores (except physical symptoms) in experimental group were much higher (P<0.05). No statistical significant difference was found in immune index between two groups before intervention (P>0.05). Differences of CD3+ and CD4+ before and after intervention were both statistically significant (P<0.05), so did free cortisol level (P<0.05). Conclusion: Comprehensive psychological intervention can effectively relieve pain, improve immune functions and enhance quality of life for patients suffering from lung cancer surgery. PMID:27022366

  6. Effect of exposure to dust on lung function of cement factory workers.

    PubMed

    Noor, H; Yap, C L; Zolkepli, O; Faridah, M

    2000-03-01

    Exposure to Portland cement dust has long been associated with the prevalence of respiratory symptoms and varying degrees of airway obstruction in man. Apart from respiratory diseases, it was also found to be the cause of lung and laryngeal cancer, gastrointestinal tumours and also dermatitis. This study was done to investigate the effect of dust exposure on ventilatory lung function of Portland cement factory workers in Rawang, Selangor. Spirometry tests of 62 male workers (exposed to total dust concentration of 10,180 micrograms/m3 and PM10 of 8049 micrograms/m3) and 70 subjects from UPM (exposed to mean total dust of 192 micrograms/m3 and PM10 of 177 micrograms/m3--controls) revealed significant differences in spirometry values between the groups. The workers showed i) significantly lower FEV1% and FEF25-75%, and higher FMFT, ii) reduced FEV1% with increasing level of dust exposure and iii) higher prevalence of respiratory symptoms. Therefore, we suggest that exposure to dust in the cement factory leads to higher incidence of respiratory symptoms and impaired lung function.

  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. Effect of exposure to dust on lung function of cement factory workers.

    PubMed

    Noor, H; Yap, C L; Zolkepli, O; Faridah, M

    2000-03-01

    Exposure to Portland cement dust has long been associated with the prevalence of respiratory symptoms and varying degrees of airway obstruction in man. Apart from respiratory diseases, it was also found to be the cause of lung and laryngeal cancer, gastrointestinal tumours and also dermatitis. This study was done to investigate the effect of dust exposure on ventilatory lung function of Portland cement factory workers in Rawang, Selangor. Spirometry tests of 62 male workers (exposed to total dust concentration of 10,180 micrograms/m3 and PM10 of 8049 micrograms/m3) and 70 subjects from UPM (exposed to mean total dust of 192 micrograms/m3 and PM10 of 177 micrograms/m3--controls) revealed significant differences in spirometry values between the groups. The workers showed i) significantly lower FEV1% and FEF25-75%, and higher FMFT, ii) reduced FEV1% with increasing level of dust exposure and iii) higher prevalence of respiratory symptoms. Therefore, we suggest that exposure to dust in the cement factory leads to higher incidence of respiratory symptoms and impaired lung function. PMID:11072491

  9. The effects of lung volume recruitment on coughing and pulmonary function in patients with ALS.

    PubMed

    Cleary, Stuart; Misiaszek, John E; Kalra, Sanjay; Wheeler, Sonya; Johnston, Wendy

    2013-03-01

    Our objective was to study the intensity and duration of the effects of lung volume recruitment, a manual breath stacking technique, on pulmonary function and coughing in individuals with amyotrophic lateral sclerosis (ALS). Twenty-nine individuals with ALS participated in this study. A cross-over research design was used to compare effects of lung volume recruitment to a control condition. Treatment outcome measures included forced vital capacity (FVC), sniff nasal pressure (SnP) and peak cough flow (PCF). Results demonstrated that LVR had a significantly positive effect on FVC for up to 15 min following treatment but did not have a facilitative effect on SnP at any time-point. LVR had a significantly positive effect on PCF during unassisted coughing at both 15 min and 30 min following treatment, and there was no significant decrease in flow rates from baseline to 30 min later. In conclusion, lung volume recruitment may be an effective treatment for improving coughing and pulmonary function in individuals with ALS. Future research should be focused on determining patient characteristics that contribute to response to treatment, as well as randomized controlled trials of the technique.

  10. 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.

  11. Structure and function of the mucus clearance system of the lung.

    PubMed

    Button, Brenda M; Button, Brian

    2013-08-01

    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. 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

  13. A Functional Landscape of Resistance to ALK Inhibition in Lung Cancer

    PubMed Central

    Wilson, Frederick H.; Johannessen, Cory M.; Piccioni, Federica; Tamayo, Pablo; Kim, Jong Wook; Van Allen, Eliezer M.; Corsello, Steven M.; Capelletti, Marzia; Calles, Antonio; Butaney, Mohit; Sharifnia, Tanaz; Gabriel, Stacey B.; Mesirov, Jill P.; Hahn, William C.; Engelman, Jeffrey A.; Meyerson, Matthew; Root, David E.; Jänne, Pasi A.; Garraway, Levi A.

    2015-01-01

    Summary We conducted a large-scale functional genetic study to characterize mechanisms of resistance to ALK inhibition in ALK-dependent lung cancer cells. We identify members of known resistance pathways and additional putative resistance drivers. Among the latter were members of the P2Y purinergic receptor family of G-protein coupled receptors (P2Y1, P2Y2, and P2Y6). P2Y receptors mediated resistance in part through a protein kinase C (PKC)-dependent mechanism. Moreover, PKC activation alone was sufficient to confer resistance to ALK inhibitors whereas combined ALK and PKC inhibition restored sensitivity. We observed enrichment of gene signatures associated with several resistance drivers (including P2Y receptors) in crizotinib-resistant ALK-rearranged lung tumors compared to treatment-naïve controls, supporting a role for identified resistance mechanisms in clinical resistance. PMID:25759024

  14. Respiratory symptoms, lung function, and pneumoconiosis among self employed dental technicians.

    PubMed Central

    Choudat, D; Triem, S; Weill, B; Vicrey, C; Ameille, J; Brochard, P; Letourneux, M; Rossignol, C

    1993-01-01

    From the registry of self employed workers living in Paris, a group of 105 dental technicians was studied to evaluate occupational exposure, to determine respiratory manifestations, and to investigate immune disturbances. Seventy one dental technicians (age range 43-68: group D), 34 dental technicians younger than 43 or older than 68 (group d), and 68 control workers (age range 43-66: group C) were investigated. The demographic characteristics and the smoking habits of the groups D and C did not differ significantly. The dental technicians often worked alone (43.7%) or in small laboratories without adequate dust control. The mean duration of their exposure was long (group D 34.0 (SD 8.4) years). The prevalence of respiratory symptoms did not differ between groups D and C except for the occurrence of increased cough and phlegm lasting for three weeks or more over the past three years (group D 16.9%, group C 2.9%, p < 0.007). The effect of cigarette smoking on respiratory symptoms and lung function was obvious. All mean values of lung function for dental technicians and controls were within normal limits. Significant decreases in all mean lung function values were found among smokers by comparison with non-smokers, however, and a positive interaction with occupational exposure was established. The x ray films of dental technicians (n = 102, groups D and d) were read independently by four readers and recorded according to the International Labour Office classification of pneumoconioses. The prevalence of small opacities greater than 1/0 was 11.8% with a significant increase with duration of exposure. The prevalence among dental technicians with 30 years or exposure or more was significantly higher (22.2%) than those with less than 30 years (3.5, p < 0.004). The prevalence of autoantibodies (rheumatoid factors, antinuclear antibodies, and antihistone antibodies) was not significantly different in the groups D and C. When positive, autoantibodies only occurred at low

  15. Functional characterisation of human pulmonary monocyte-like cells in lipopolysaccharide-mediated acute lung inflammation

    PubMed Central

    2014-01-01

    Background We have previously reported the presence of novel subpopulations of pulmonary monocyte-like cells (PMLC) in the human lung; resident PMLC (rPMLC, HLA-DR+CD14++CD16+cells) and inducible PMLC (iPMLC, HLA-DR+CD14++CD16- cells). iPMLC are significantly increased in bronchoalveolar lavage (BAL) fluid following inhalation of lipopolysaccharide (LPS). We have carried out the first functional evaluation of PMLC subpopulations in the inflamed lung, following the isolation of these cells, and other lineages, from BAL fluid using novel and complex protocols. Methods iPMLC, rPMLC, alveolar macrophages (AM), neutrophils, and regulatory T cells were quantified in BAL fluid of healthy subjects at 9 hours post-LPS inhalation (n = 15). Cell surface antigen expression by iPMLC, rPMLC and AM and the ability of each lineage to proliferate and to undergo phagocytosis were investigated using flow cytometry. Basal cytokine production by iPMLC compared to AM following their isolation from BAL fluid and the responsiveness of both cell types following in vitro treatment with the synthetic corticosteroid dexamethasone were assessed. Results rPMLC have a significantly increased expression of mature macrophage markers and of the proliferation antigen Ki67, compared to iPMLC. Our cytokine data revealed a pro-inflammatory, corticosteroid-resistant phenotype of iPMLC in this model. Conclusions These data emphasise the presence of functionally distinct subpopulations of the monocyte/macrophage lineage in the human lung in experimental acute lung inflammation. PMID:24684897

  16. 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

  17. Functional importance of the NH2-terminal insertion sequence of lung surfactant protein B

    PubMed Central

    Frey, Shelli L.; Pocivavsek, Luka; Waring, Alan J.; Walther, Frans J.; Hernandez-Juviel, Jose M.; Ruchala, Piotr

    2010-01-01

    Lung surfactant protein B (SP-B) is required for proper surface activity of pulmonary surfactant. In model lung surfactant lipid systems composed of saturated and unsaturated lipids, the unsaturated lipids are removed from the film at high compression. It is thought that SP-B helps anchor these lipids closely to the monolayer in three-dimensional cylindrical structures termed “nanosilos” seen by atomic force microscopy imaging of deposited monolayers at high surface pressures. Here we explore the role of the SP-B NH2 terminus in the formation and stability of these cylindrical structures, specifically the distribution of lipid stack height, width, and density with four SP-B truncation peptides: SP-B 1–25, SP-B 9–25, SP-B 11–25, and SP-B 1–25Nflex (prolines 2 and 4 substituted with alanine). The first nine amino acids, termed the insertion sequence and the interface seeking tryptophan residue 9, are shown to stabilize the formation of nanosilos while an increase in the insertion sequence flexibility (SP-B 1–25Nflex) may improve peptide functionality. This provides a functional understanding of the insertion sequence beyond anchoring the protein to the two-dimensional membrane lining the lung, as it also stabilizes formation of nanosilos, creating reversible repositories for fluid lipids at high compression. In lavaged, surfactant-deficient rats, instillation of a mixture of SP-B 1–25 (as a monomer or dimer) and synthetic lung lavage lipids quickly improved oxygenation and dynamic compliance, whereas SP-B 11–25 surfactants showed oxygenation and dynamic compliance values similar to that of lipids alone, demonstrating a positive correlation between formation of stable, but reversible, nanosilos and in vivo efficacy. PMID:20023175

  18. Lung function and general illness symptoms in a semiconductor manufacturing facility.

    PubMed

    Luo, J C; Hsu, K H; Hsieh, L L; Wong, C J; Chang, M J

    1998-10-01

    Large quantities of potent gases, dopants, photoactive chemicals (photoresists, photoinitiators), solvents, and ionizing radiation are used in the semiconductor manufacturing process, but little is known about the occurrence of respiratory disease from exposures in this industry. The purpose of this study was to assess the pulmonary risk by conducting pulmonary function tests and symptoms survey in a semiconductor plant in Taiwan. This study is part of a clinical survey conducted on 926 workers in a semiconductor plant in Taiwan in July 1995. The study items included a standard self-administered questionnaire, chest x-rays, pulmonary function tests, and physical examinations in 249 workers. There was a borderline significance of higher prevalence (P = 0.06) of restrictive lung abnormality in male photolithographic workers (4 of 21; 19.1%) than in male control workers (0 of 17; 0%), and the smoking- and age-adjusted odds ratio was 4.1 (95% confidence interval [CI], 0.41-41.6). There was a significantly higher prevalence (P = 0.02) of restrictive lung abnormality in male ion-implantation workers (5 of 19; 26.3%) than in male control workers (0 of 17; 0%), and the smoking- and age-adjusted odds ratio was 3.7 (95% CI, 0.52-26.7). There were significantly higher prevalences of airway irritation, eye irritation, headache, stress, tiredness, and poor memory in female photolithographic or etch/diffusion workers than in control workers. This study suggests that restrictive lung abnormality is a potential health effect in male silicon-wafer fabrication workers in the semiconductor industry. The tasks of male process, maintenance, and equipment engineers put them at risk for intermittent short-term peak exposure. This may account for a higher prevalence of mild restrictive lung abnormality among male engineers of photolithographic and ionimplantation sections. The findings of this medical surveillance are tentative, but they suggest that further investigation of the etiologic

  19. 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. PMID:25997942

  20. 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.

  1. Joint Effects of Smoking and Sedentary Lifestyle on Lung Function in African Americans: The Jackson Heart Study Cohort

    PubMed Central

    Campbell Jenkins, Brenda W.; Sarpong, Daniel F.; Addison, Clifton; White, Monique S.; Hickson, DeMarc A.; White, Wendy; Burchfiel, Cecil

    2014-01-01

    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. PMID:24477212

  2. 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

    2014-02-01

    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. PMID:24477212

  3. Fetal dexamethasone exposure accelerates development of renal function: relationship to dose, cell differentiation and growth inhibition.

    PubMed

    Slotkin, T A; Seidler, F J; Kavlock, R J; Gray, J A

    1992-02-01

    Fetal exposure to high doses of glucocorticoids slows cellular development and impairs organ performance, in association with growth retardation. Nevertheless, low doses of glucocorticoids may enhance cell differentiation and accelerate specific functions. The current study examined this apparent paradox in the developing rat kidney, using doses of dexamethasone that span the threshold for growth impairment: 0.05 or 0.2 mg/kg given on gestational days 17, 18 and 19. At the lower dose, which did not significantly retard body growth, the postnatal development of tubular reabsorptive capabilities for sodium, potassium, osmotic particles, water and urea was accelerated. These effects were less notable at the higher dose, which caused initial body growth impairment. The selectivity toward promotion of tubular function was evidenced by the absence of effect of either dose of dexamethasone on development of glomerular filtration rate. Because of the wide spectrum of dexamethasone's effects on tubular function, we also assessed fetal kidney adenylate cyclase as a means of detecting altered cell differentiation in the prenatal period during which dexamethasone was given. Either glucocorticoid dose increased the total adenylate cyclase catalytic activity (assessed with forskolin). Thus, the net effect of fetal dexamethasone exposure on development of renal excretory capabilities probably represents the summation of promoted cell differentiation and slowed development consequent to growth retardation. At low dose levels, the former effect predominates, leading to enhanced functional development, whereas higher doses that interfere with general growth and development can offset the direct promotional effect.

  4. 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

  5. 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

  6. 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.

  7. Pneumonia in Childhood and Impaired Lung Function in Adults: A Longitudinal Study

    PubMed Central

    Chan, Johnny Y.C.; Stern, Debra A.; Guerra, Stefano; Wright, Anne L.; Morgan, Wayne J.

    2015-01-01

    BACKGROUND: Diminished lung function and increased prevalence of asthma have been reported in children with a history of early lower respiratory illnesses (LRIs), including pneumonia. Whether these associations persist up to adulthood has not been established. METHODS: As part of the prospective Tucson Children's Respiratory Study, LRIs during the first 3 years of life were ascertained by pediatricians. Spirometry was performed at ages 11, 16, 22, and 26 years. The occurrence of asthma/wheeze during the previous year was ascertained at ages 11, 13, 16, 18, 22, 24, 26, and 29 years. Longitudinal random effects models and generalized estimating equations were used to assess the relation of LRIs to lung function and asthma. RESULTS: Compared with participants without early-life LRIs, those with pneumonia had the most severe subsequent lung function impairment, with mean ± SE deficits of −3.9% ± 0.9% (P < .001) and −2.5% ± 0.8% (P = .001) for pre- and post-bronchodilator FEV1:FVC ratio from age 11 to 26 years, respectively. Pneumonia was associated with increased risk for asthma (odds ratio [OR]: 1.95; 95% confidence interval [CI]: 1.11–3.44) and wheeze (OR: 1.94; 95% CI: 1.28–2.95) over the same age range. Early non-pneumonia LRIs were associated with mildly impaired pre-bronchodilator FEV1 (−62.8 ± 27.9mL, P = .024) and FEV1:FVC ratio (−1.1 ± 0.5%, P = .018), and wheeze (OR: 1.37; 95% CI: 1.09–1.72). CONCLUSIONS: Early pneumonia is associated with asthma and impaired airway function, which is partially reversible with bronchodilators and persists into adulthood. Early pneumonia may be a major risk factor for adult chronic obstructive pulmonary disease. PMID:25733757

  8. 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.

  9. Surface biophysics of the surface monolayer theory is incompatible with regional lung function.

    PubMed Central

    Scarpelli, E M; Mautone, A J

    1994-01-01

    The surface monolayer theory of Clements was tested on open surface films of calf lung surfactant extract in a leak-free vertical film surface balance in which alveolar area (A) changes in each lung zone were simulated in accordance with the theory. We found that: 1) physiologically necessary low surface tension (gamma), < 4 dyn/cm, was sustained only by continuous film compression ("expiration"); 2) compression from A equivalent to total lung capacity to functional residual capacity produced fleeting gamma reduction in all zones and quick reversal to high gamma with A changes that simulated tidal volume (VT) breathing at both 14 (adult) and 40 (neonatal) cpm; 3) phase differences between gamma and A axes of VT loops that indicate mixed surface film composition may be attributable to film inertia and viscoelasticity; 4) estimated alveolar retraction pressure due to gamma (P gamma) exceeds "net" transpulmonary pressure, i.e., favors alveolar collapse, under virtually all conditions of the theory in all zones; 5) return to transient, fleeting low gamma in successive VT cycles was determined by the inherent difference in compression and decompression rates, which results in exhaustion of available A in very few cycles; 6) the "sigh", which restores stable low gamma according to the theory, actually produced unstable high gamma during virtually all phases of the maneuver. In contrast, closed bubble films of the surfactant were structurally stable and produce stable near 0 gamma and P gamma. Images FIGURE 4 FIGURE 5 PMID:7811918

  10. Ventilation-perfusion imaging in evaluating regional lung function in nonpenetrating injury to the chest.

    PubMed

    Van Eeden, S F; Klopper, J F; Alheit, B; Bardin, P G

    1989-03-01

    The extent of chest wall and lung injury after nonpenetrating injury to the chest (NIC) determine how aggressive and invasive management modalities should be. We investigated the value of ventilation (133Xe) and perfusion (99mTc) studies as indicators of extent of lung injury in 28 patients with moderate to severe unilateral NIC. The ventilation-perfusion (V/Q) abnormalities were compared with parameters conventionally used to evaluate NIC. All studies were carried out within 24 h of NIC and repeated 24 h later. Ventilation (p less than 0.001) and perfusion (p less than 0.01) abnormalities were more extensive soon after NIC than suggested by chest roentgenograms. Chest x-ray film changes lagged behind V/Q changes on admission and also after 24 h. The extent of ventilation, perfusion, and chest x-ray film abnormalities on admission were all predictors of increased morbidity. V/Q studies may be useful to define the extent as well as the changes in regional lung function following NIC.

  11. Lung function after allogeneic bone marrow transplantation for leukaemia or lymphoma.

    PubMed

    Nysom, K; Holm, K; Hesse, B; Ulrik, C S; Jacobsen, N; Bisgaard, H; Hertz, H

    1996-05-01

    Longitudinal data were analysed on the lung function of 25 of 29 survivors of childhood leukaemia or lymphoma, who had been conditioned with cyclophosphamide and total body irradiation before allogeneic bone marrow transplantation, to test whether children are particularly vulnerable to pulmonary damage after transplantation. None developed chronic graft-versus-host disease. Transfer factor and lung volumes were reduced immediately after bone marrow transplantation, but increased during the following years. However, at the last follow up, 4-13 years (median 8) after transplantation, patients had significantly reduced transfer factor, total lung capacity, and forced vital capacity (-1.0, -1.2, and -0.8 SD score, respectively), and increased ratio of forced expiratory volume in one second to forced vital capacity (+0.9 SD score). None of the patients had pulmonary symptoms, and changes were unrelated to their age at bone marrow transplantation. In conclusion, patients had subclinical restrictive pulmonary disease at a median of eight years after total body irradiation and allogeneic bone marrow transplantation.

  12. Increased numbers but functional defects of CD56+CD3+ cells in lung cancer.

    PubMed

    Al Omar, Suliman Y; Marshall, Ernie; Middleton, Derek; Christmas, Stephen E

    2012-07-01

    CD56+ T cells were studied in samples of peripheral blood from small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) patients compared with healthy controls. Relative numbers of CD56+CD3+ cells were increased in NSCLC (P = 0.001) and SCLC (P = 0.002) compared with normal subjects but their ability to respond to activation by up-regulating CD25 or producing IFN-γ were both significantly impaired. Expression of the killer-immunoglobulin-like receptor CD158a was significantly lower on CD56+CD3+ cells in SCLC than controls and also in early stage compared with late stage NSCLC patients. Mean levels of CD158e were higher in NSCLC patients than controls. CD158e levels on CD56+CD3+ cells were increased in the presence of its ligand HLA-Bw4 compared with controls. Although the precise role of CD56+CD3+ cells is not clear, they appear to be functionally impaired in lung cancer, which may have implications for a reduction of direct or indirect anti-tumour responses.

  13. Quantitative study of lung perfusion SPECT scanning and pulmonary function testing for early radiation-induced lung injury in patients with locally advanced non-small cell lung cancer

    PubMed Central

    ZHANG, WEI; WANG, JIEZHONG; TANG, MINGDENG; PAN, JIANJI; BAI, PENGGANG; LIN, DUANYU; QIAN, FEIYU; LIN, FENGJIE; YANG, XUEQIN; ZHANG, SHENGLI

    2012-01-01

    Radiation lung injury is a common side-effect of pulmonary radiotherapy. The aim of this study was to quantitatively assess early changes in lung perfusion single photon emission computed tomography (SPECT) scanning and pulmonary function testing (PFT) prior to and after intensity modulated radiotherapy (IMRT) for patients suffering from locally advanced non-small cell lung cancer (LANSCLC). Twenty patients with LANSCLC received lung perfusion SPECT scanning and PFT prior to IMRT and immediately after IMRT. Lung perfusion index (LPI) was calculated after the quantification of perfusion SPECT images. The LPI of the two groups was analyzed by matched t-test. The radioactive count of each layer of single lung was added to obtain the sum of the irradiated area. The percentage of the irradiated area of single lung was calculated. Linear correlation analysis was carried out between the percentage of the irradiated area and LPI in order to verify the validity of LPI. In this study, LPI and the percentage of the irradiated area of single lung exhibited an excellent correlation either prior to or after IMRT (r=0.820 and r=0.823, respectively; p<0.001). There was no statistically significant difference between pre-IMRT LPI and post-IMRT LPI (p=0.135). LPI in the group receiving a radical dose had no statistically significant difference (p=0.993), however, it showed a statistically significant difference in the group receiving a non-radical dose (p=0.025). In the non-radical dose group, the post-IMRT LPI was larger compared to pre-IMRT. None of the parameters of PFT exhibited a statistically significant difference prior to and after IMRT (p>0.05). The quantitative method of lung perfusion SPECT scanning can be used to evaluate changes in perfusion early in patients receiving a non-radical dose (BED ≤126,500 cGy) IMRT. Evaluating early changes in global lung function using the current method of PFT is difficult, since time can be a contributing factor for radiation

  14. Investigation of the effect of high +Gz accelerations on human cardiac function.

    PubMed

    Jamshidi, M; Ahmadian, M T

    2013-11-01

    This study investigates the effect of body acceleration on human cardiac function. Finite element analysis is conducted to simulate geometrical and mechanical properties of human heart. Heart geometrical modeling in three-dimension is performed by segmentation of cardiac MRI images. The nonlinear mechanical behavior of myocardium is modeled by Mooney-Rivlin, Polynomial, Ogden and Yeoh hyperelastic material models. Stress-strain curves of myocardial tissue are obtained from experimental compression tests on bovine heart samples. The experimental results are employed for the evaluation of material coefficients by the nonlinear least squares method. Among hyperelastic models, the Yeoh model presents the best fit with experimental stress-strain curve and is used for finite element simulation of heart tissue. Obtained material coefficients are implemented into the constructed heart model and nonlinear finite element analysis is performed for different levels of acceleration in upward direction of vertical axis of body during the rapid filling phase of cardiac cycle. Based on the finite element analysis, ventricular volume change, stress and deformation of heart model are evaluated. It is revealed that when the body is subjected to high accelerations, structural changes in the heart reduce blood supply to body up to 7.2% at +6G.

  15. 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

  16. 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.

  17. GPU Accelerated Implementation of Density Functional Theory for Hybrid QM/MM Simulations.

    PubMed

    Nitsche, Matías A; Ferreria, Manuel; Mocskos, Esteban E; González Lebrero, Mariano C

    2014-03-11

    The hybrid simulation tools (QM/MM) evolved into a fundamental methodology for studying chemical reactivity in complex environments. This paper presents an implementation of electronic structure calculations based on density functional theory. This development is optimized for performing hybrid molecular dynamics simulations by making use of graphic processors (GPU) for the most computationally demanding parts (exchange-correlation terms). The proposed implementation is able to take advantage of modern GPUs achieving acceleration in relevant portions between 20 to 30 times faster than the CPU version. The presented code was extensively tested, both in terms of numerical quality and performance over systems of different size and composition. PMID:26580175

  18. 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.

  19. Impact of chronic systolic heart failure on lung structure-function relationships in large airways.

    PubMed

    Chase, Steven C; Wheatley, Courtney M; Olson, Lyle J; Beck, Kenneth C; Wentz, Robert J; Snyder, Eric M; Taylor, Bryan J; Johnson, Bruce D

    2016-07-01

    Heart failure (HF) is often associated with pulmonary congestion, reduced lung function, abnormal gas exchange, and dyspnea. We tested whether pulmonary congestion is associated with expanded vascular beds or an actual increase in extravascular lung water (EVLW) and how airway caliber is affected in stable HF Subsequently we assessed the influence of an inhaled short acting beta agonist (SABA). Thirty-one HF (7F; age, 62 ± 11 years; ht. 175 ± 9 cm; wt. 91 ± 17 kg; LVEF, 28 ± 15%) and 29 controls (11F; age; 56 ± 11 years; ht. 174 ± 8 cm; wt. 77 ± 14 kg) completed the study. Subjects performed PFTs and a chest computed tomography (CT) scan before and after SABA CT measures of attenuation, skew, and kurtosis were obtained from areas of lung tissue to assess EVLW Airway luminal areas and wall thicknesses were also measured : CT tissue density suggested increased EVLW in HF without differences in the ratio of airway wall thickness to luminal area or luminal area to TLC (skew: 2.85 ± 1.08 vs. 2.11 ± 0.79, P < 0.01; Kurtosis: 15.5 ± 9.5 vs. 9.3 ± 5.5 P < 0.01; control vs. HF). PFTs were decreased in HF at baseline (% predicted FVC:101 ± 15% vs. 83 ± 18%, P < 0.01;FEV1:103 ± 15% vs. 82 ± 19%, P < 0.01;FEF25-75: 118 ± 36% vs. 86 ± 36%, P < 0.01; control vs. HF). Airway luminal areas, but not CT measures, were correlated with PFTs at baseline. The SABA cleared EVLW and decreased airway wall thickness but did not change luminal area. Patients with HF had evidence of increased EVLW, but not an expanded bronchial circulation. Airway caliber was maintained relative to controls, despite reductions in lung volume and flow rates. SABA improved lung function, primarily by reducing EVLW.

  20. 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

  1. Radiological progression and lung function in silicosis: a ten year follow up study.

    PubMed

    Ng, T P; Chan, S L; Lam, K P

    1987-07-18

    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.

  2. 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. PMID:21310877

  3. Relationship between body composition and both cardiovascular risk factors and lung function in systemic sclerosis.

    PubMed

    Caramaschi, Paola; Biasi, Domenico; Caimmi, Cristian; Barausse, Giovanni; Gatti, Davide; Ferrari, Marcello; Pieropan, Sara; Sabbagh, Dania; Adami, Silvano

    2014-01-01

    The aims of this study were to evaluate body composition in systemic sclerosis (SSc) and to assess its association with the traditional risk factors for atherosclerosis and parameters of lung function. Eighty-six patients affected by SSc (13 men and 73 women, mean age 58.5 years, mean disease duration 10.7 years, 31 with diffuse form and 55 with limited pattern) underwent evaluation of body composition using a dual-energy X-ray (DXA) fan beam densitometer (GE Lunar iDXA) in order to assess total and regional body fat mass and fat-free mass. Clinical features, pulmonary function parameters, and the concomitant presence of the traditional cardiovascular risk factors were recorded. Android fat resulted to be higher in SSc patients with coexistence of hypercholesterolemia (P = 0.021), hypertension (P = 0.028), and overweight/obesity (P < 0.001) and positively correlated with body mass index (P < 0.001). Forced vital capacity (FVC) was inversely correlated with android fat (P = 0.034) and with the android fat/gynoid fat ratio (P = 0.013) and positively correlated with android lean (P = 0.041); the correlations were improved when FVC data were adjusted for sex, age, disease duration, and smoking habits (P = 0.010 for android fat, P = 0.010 for android fat/gynoid fat ratio, P = 0.011 for android lean). In this study, we showed that visceral abdominal fat, measured by DXA, is correlated with the main cardiovascular risk factors and lung volumes in SSc patients. Longitudinal studies are needed to evaluate if decrease of abdominal fat would improve lung function. PMID:24052413

  4. 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.

  5. Nebulised 7% hypertonic saline improves lung function and quality of life in bronchiectasis.

    PubMed

    Kellett, Fiona; Robert, Niven M

    2011-12-01

    Sputum retention is a distressing feature of non-cystic fibrosis bronchiectasis and has been shown to contribute to the vicious cycle of infection seen in this disease. In a previous study we demonstrated that nebulised 7% hypertonic saline was both safe and effective in this patient population. Patients with a clinical diagnosis of non-cystic fibrosis bronchiectasis, confirmed by HRCT, were entered into a randomised single blind cross-over study to evaluate 0.9% sodium chloride (IS) and 7% hypertonic saline (HS). Following a 4 week run in patients received a random order active HS or IS daily for 3 months. A 4 week wash-out phase was included between phases. We report lung function, quality of life, and health care utilisation responses. 32 patients mean age 56.6 years (SD 14.6), 16 male, were recruited of which 28 were randomised and completed the study. Lung function (%change from baseline) improved in HS vs. IS (FEV(1): 15.1, 1.8 p<0.01; FVC: 11.2, 0.7 p<0.01. SGRQ improved significantly from baseline (HS 6.0, IS 1.2; p<0.05). There were reductions in annualised antibiotic usage (HS 2.4, IS 5.4 courses per patient per year), annualised emergency health care utilisation visits were reduced (HS 2.1, IS 4.9 events per patient per year). There were also improvements in sputum viscosity and ease of expectoration (visual analogue scale). Regular use of 7% hypertonic saline improves lung function, quality of life and health care utilisation in non-cystic fibrosis bronchiectasis patients. PMID:22018993

  6. Influence of childhood growth on asthma and lung function in adolescence

    PubMed Central

    Sonnenschein-van der Voort, Agnes M.M.; Howe, Laura D.; Granell, Raquel; Duijts, Liesbeth; Sterne, Jonathan A.C.; Tilling, Kate; Henderson, A. John

    2015-01-01

    Background Low birth weight and rapid infant growth in early infancy are associated with increased risk of childhood asthma, but little is known about the role of postinfancy growth in asthmatic children. Objectives We sought to examine the associations of children's growth patterns with asthma, bronchial responsiveness, and lung function until adolescence. Methods Individual growth trajectories from birth until 10 years of age were estimated by using linear spline multilevel models for 9723 children participating in a population-based prospective cohort study. Current asthma at 8, 14, and 17 years of age was based on questionnaires. Lung function and bronchial responsiveness or reversibility were measured during clinic visits at 8 and 15 years of age. Results Rapid weight growth between 0 and 3 months of age was most consistently associated with increased risks of current asthma at the ages of 8 and 17 years, bronchial responsiveness at age 8 years, and bronchial reversibility at age 15 years. Rapid weight growth was associated with lung function values, with the strongest associations for weight gain between 3 and 7 years of age and higher forced vital capacity (FVC) and FEV1 values at age 15 years (0.12 [95% CI, 0.08 to 0.17] and 0.11 [95% CI, 0.07 to 0.15], z score per SD, respectively) and weight growth between 0 and 3 months of age and lower FEV1/FVC ratios at age 8 and 15 years (−0.13 [95% CI, −0.16 to −0.10] and −0.04 [95% CI, −0.07 to −0.01], z score per SD, respectively). Rapid length growth was associated with lower FVC and FVC1 values at age 15 years. Conclusion Faster weight growth in early childhood is associated with asthma and bronchial hyperresponsiveness, and faster weight growth across childhood is associated with higher FVC and FEV1 values. PMID:25577593

  7. 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

  8. 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.

  9. 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

  10. 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

  11. Long-term stable lung function and second uncomplicated pregnancy on sirolimus in lymphangioleiomyomatosis (LAM).

    PubMed

    Faehling, Martin; Wienhausen-Wilke, Vera; Fallscheer, Sabine; Trinajstic-Schulz, B; Weber, J; Leschke, Matthias

    2015-01-01

    We present a patient with lymphangioleiomyomatosis (LAM) on long-term sirolimus (now 79 months) who has had a second successful pregnancy. The second pregnancy on uninterrupted low-dose sirolimus (plasma levels 3-5 mg/L) was uncomplicated both with respect to mother and child suggesting that low-dose sirolimus might be safe in selected pregnant patients with stable LAM. The long-term time course in this patient is in agreement with recent reports of a long-term beneficial effect of sirolimus in LAM. In this patient, the pregnancies did not seem to impair the long-term improvement of lung-function on sirolimus.

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

    PubMed Central

    2013-01-01

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

  13. 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

  14. Different approaches for quantifying ventilation distribution and lung tissue properties by functional EIT.

    PubMed

    Hahn, G; Dittmar, J; Just, A; Quintel, M; Hellige, G

    2010-08-01

    We investigated five different methods which can be applied to quantitatively construct functional tomograms of the lungs. The focus was on the sensitivity of functional tomograms to errors in acquired data. To quantify this sensitivity, theoretical, error-free data sets of well-known properties were artificially generated based on a 'living thorax model'. Physiological time courses and a typical distribution of errors caused by a typical Goe-MF II EIT system were used for the calculations which encompassed a range up to 50 times greater than the initial error level (4 microV(rms max)-400 microV(rms max)). Additionally, low-pass filtering and principal component analysis (PCA) were used to quantify the effect of preprocessing the raw data. The results demonstrate that all methods based on fitting the local to the global time course were superior to the common functional tomograms utilizing standard deviation or maximum and minimum detection. Ventilation distribution was best quantified by the so-called VT methods. Filling capacity--a lung tissue property--was least dependent on increasing error levels. The errors introduced by filtering are significant with respect to a quantitative analysis of ventilation distribution. A preprocessing of raw data by applying a PCA performed well on the data sets which had been constructed but were, nonetheless, realistic. This approach appears to be highly promising for application on real data which is known to be erroneous.

  15. Evaluation of the reproducibility of lung motion probability distribution function (PDF) using dynamic MRI

    NASA Astrophysics Data System (ADS)

    Cai, Jing; Read, Paul W.; Altes, Talissa A.; Molloy, Janelle A.; Brookeman, James R.; Sheng, Ke

    2007-01-01

    Treatment planning based on probability distribution function (PDF) of patient geometries has been shown a potential off-line strategy to incorporate organ motion, but the application of such approach highly depends upon the reproducibility of the PDF. In this paper, we investigated the dependences of the PDF reproducibility on the imaging acquisition parameters, specifically the scan time and the frame rate. Three healthy subjects underwent a continuous 5 min magnetic resonance (MR) scan in the sagittal plane with a frame rate of approximately 10 f s-1, and the experiments were repeated with an interval of 2 to 3 weeks. A total of nine pulmonary vessels from different lung regions (upper, middle and lower) were tracked and the dependences of their displacement PDF reproducibility were evaluated as a function of scan time and frame rate. As results, the PDF reproducibility error decreased with prolonged scans and appeared to approach equilibrium state in subjects 2 and 3 within the 5 min scan. The PDF accuracy increased in the power function with the increase of frame rate; however, the PDF reproducibility showed less sensitivity to frame rate presumably due to the randomness of breathing which dominates the effects. As the key component of the PDF-based treatment planning, the reproducibility of the PDF affects the dosimetric accuracy substantially. This study provides a reference for acquiring MR-based PDF of structures in the lung.

  16. 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.

  17. Dust exposure and impairment of lung function at a small iron foundry in a rapidly developing country

    PubMed Central

    Gomes, J; Lloyd, O; Norman, N; Pahwa, P

    2001-01-01

    OBJECTIVES—A cross sectional prospective study was carried out among iron foundry workers (exposed) and soft drink bottling and supply company workers (unexposed) to assess their occupational exposure to ambient respiratory dust in their work environment and its effect on their lung function profile.
PARTICIPANTS—Lung function was measured in 81 exposed and 113 unexposed workers. Personal respirable dust concentrations were measured for all the exposed and the unexposed workers. Information on respiratory signs and symptoms was also collected from the participants.
RESULTS—Among the exposed workers, midexpiratory flow (FEF25-75), forced expiratory volume in 1 second (FEV1), peak expiratory flow (PEF), FEV1/FVC, and FEV1/VC ratios were significantly lower whereas the vital capacity (VC) and forced vital capacity (FVC) were non-significantly higher. Job at the iron foundry was a significant predictor of lung function. Exposure to high concentration of respirable dust at the iron foundry was also a significant predictor. Workers working in high exposure areas (general works, furnace, continuous casting areas, and fabrication workshop) had lower lung function values than workers in medium and low exposure areas. Smoking did not enhance the effects of exposure to dust on lung function.
CONCLUSIONS—Exposure to respirable dust was higher among the iron foundry workers; and among these, general, furnace, rolling mill, and fabrication workers had higher exposures to dust than did workers in continuous casting, the mechanical workshop, and the bottling plant. Job type and exposure to dust were significant predictors of lung function. Implementation of industrial hygiene and proper and efficient use of personal protection equipment while at work could help to protect the respiratory health of industrial workers.


Keywords: lung function; dust exposure; foundry; smoking; personal protection PMID:11555687

  18. Tables of phase functions, opacities, albedos, equilibrium temperatures, and radiative accelerations of dust grains in exoplanets

    NASA Astrophysics Data System (ADS)

    Budaj, J.; Kocifaj, M.; Salmeron, R.; Hubeny, I.

    2015-11-01

    There has been growing observational evidence for the presence of condensates in the atmospheres and/or comet-like tails of extrasolar planets. As a result, systematic and homogeneous tables of dust properties are useful in order to facilitate further observational and theoretical studies. In this paper we present calculations and analysis of non-isotropic phase functions, asymmetry parameter (mean cosine of the scattering angle), absorption and scattering opacities, single scattering albedos, equilibrium temperatures, and radiative accelerations of dust grains relevant for extrasolar planets. Our assumptions include spherical grain shape, Deirmendjian particle size distribution, and Mie theory. We consider several species: corundum/alumina, perovskite, olivines with 0 and 50 per cent iron content, pyroxenes with 0, 20, and 60 per cent iron content, pure iron, carbon at two different temperatures, water ice, liquid water, and ammonia. The presented tables cover the wavelength range of 0.2-500 μm and modal particle radii from 0.01 to 100 μm. Equilibrium temperatures and radiative accelerations assume irradiation by a non-blackbody source of light with temperatures from 7000 to 700 K seen at solid angles from 2π to 10-6 sr. The tables are provided to the community together with a simple code which allows for an optional, finite, angular dimension of the source of light (star) in the phase function.

  19. HOIL-1L Functions as the PKCζ Ubiquitin Ligase to Promote Lung Tumor Growth

    PubMed Central

    Queisser, Markus A.; Dada, Laura A.; Deiss-Yehiely, Nimrod; Angulo, Martin; Zhou, Guofei; Kouri, Fotini M.; Knab, Lawrence M.; Liu, Jing; Stegh, Alexander H.; DeCamp, Malcolm M.; Budinger, G. R. Scott; Chandel, Navdeep S.; Ciechanover, Aaron; Iwai, Kazuhiro

    2014-01-01

    Rationale: Protein kinase C zeta (PKCζ) has been reported to act as a tumor suppressor. Deletion of PKCζ in experimental cancer models has been shown to increase tumor growth. However, the mechanisms of PKCζ down-regulation in cancerous cells have not been previously described. Objectives: To determine the molecular mechanisms that lead to decreased PKCζ expression and thus increased survival in cancer cells and tumor growth. Methods: The levels of expression of heme-oxidized IRP2 ubiquitin ligase 1L (HOIL-1L), HOIL-1–interacting protein (HOIP), Shank-associated RH domain-interacting protein (SHARPIN), and PKCζ were analyzed by Western blot and/or quantitative real-time polymerase chain reaction in different cell lines. Coimmunoprecipitation experiments were used to demonstrate the interaction between HOIL-1L and PKCζ. Ubiquitination was measured in an in vitro ubiquitination assay and by Western blot with specific antibodies. The role of hypoxia-inducible factor (HIF) was determined by gain/loss-of-function experiments. The effect of HOIL-1L expression on cell death was investigated using RNA interference approaches in vitro and on tumor growth in mice models. Increased HOIL-1L and decreased PKCζ expression was assessed in lung adenocarcinoma and glioblastoma multiforme and documented in several other cancer types by oncogenomic analysis. Measurements and Main Results: Hypoxia is a hallmark of rapidly growing solid tumors. We found that during hypoxia, PKCζ is ubiquitinated and degraded via the ubiquitin ligase HOIL-1L, a component of the linear ubiquitin chain assembly complex (LUBAC). In vitro ubiquitination assays indicate that HOIL-1L ubiquitinates PKCζ at Lys-48, targeting it for proteasomal degradation. In a xenograft tumor model and lung cancer model, we found that silencing of HOIL-1L increased the abundance of PKCζ and decreased the size of tumors, suggesting that lower levels of HOIL-1L promote survival. Indeed, mRNA transcript levels of HOIL

  20. IL6R Variation Asp358Ala Is a Potential Modifier of Lung Function in Asthma

    PubMed Central

    Hawkins, Gregory A; Robinson, Mac B; Hastie, Annette T; Li, Xingnan; Li, Huashi; Moore, Wendy C; Howard, Timothy D; Busse, William W.; Erzurum, Serpil C.; Wenzel, Sally E.; Peters, Stephen P; Meyers, Deborah A; Bleecker, Eugene R

    2012-01-01

    Background The IL6R SNP rs4129267 has recently been identified as an asthma susceptibility locus in subjects of European ancestry but has not been characterized with respect to asthma severity. The SNP rs4129267 is in linkage disequilibrium (r2=1) with the IL6R coding SNP rs2228145 (Asp358Ala). This IL6R coding change increases IL6 receptor shedding and promotes IL6 transsignaling. Objectives To evaluate the IL6R SNP rs2228145 with respect to asthma severity phenotypes. Methods The IL6R SNP rs2228145 was evaluated in subjects of European ancestry with asthma from the Severe Asthma Research Program (SARP). Lung function associations were replicated in the Collaborative Study on the Genetics of Asthma (CSGA) cohort. Serum soluble IL6 receptor (sIL6R) levels were measured in subjects from SARP. Immunohistochemistry was used to qualitatively evaluate IL6R protein expression in BAL cells and endobronchial biopsies. Results The minor C allele of IL6R SNP rs2228145 was associated with lower ppFEV1 in the SARP cohort (p=0.005), the CSGA cohort (0.008), and in combined cohort analysis (p=0.003). Additional associations with ppFVC, FEV1/FVC, and PC20 were observed. The rs2228145 C allele (Ala358) was more frequent in severe asthma phenotypic clusters. Elevated serum sIL6R was associated with lower ppFEV1 (p=0.02) and lower ppFVC (p=0.008) (N=146). IL6R protein expression was observed in BAL macrophages, airway epithelium, vascular endothelium, and airway smooth muscle. Conclusions The IL6R coding SNP rs2228145 (Asp358Ala) is a potential modifier of lung function in asthma and may identify subjects at risk for more severe asthma. IL6 transsignaling may have a pathogenic role in the lung. PMID:22554704

  1. Existence, Functional Impairment, and Lung Repair Potential of Endothelial Colony-Forming Cells in Oxygen-Induced Arrested Alveolar Growth

    PubMed Central

    Alphonse, Rajesh S.; Vadivel, Arul; Fung, Moses; Shelley, William Chris; Critser, Paul John; Ionescu, Lavinia; O’Reilly, Megan; Ohls, Robin K.; McConaghy, Suzanne; Eaton, Farah; Zhong, Shumei; Yoder, Merv; Thébaud, Bernard

    2014-01-01

    Background Bronchopulmonary dysplasia and emphysema are life-threatening diseases resulting from impaired alveolar development or alveolar destruction. Both conditions lack effective therapies. Angiogenic growth factors promote alveolar growth and contribute to alveolar maintenance. Endothelial colony-forming cells (ECFCs) represent a subset of circulating and resident endothelial cells capable of self-renewal and de novo vessel formation. We hypothesized that resident ECFCs exist in the developing lung, that they are impaired during arrested alveolar growth in experimental bronchopulmonary dysplasia, and that exogenous ECFCs restore disrupted alveolar growth. Methods and Results Human fetal and neonatal rat lungs contain ECFCs with robust proliferative potential, secondary colony formation on replating, and de novo blood vessel formation in vivo when transplanted into immunodeficient mice. In contrast, human fetal lung ECFCs exposed to hyperoxia in vitro and neonatal rat ECFCs isolated from hyperoxic alveolar growth–arrested rat lungs mimicking bronchopulmonary dysplasia proliferated less, showed decreased clonogenic capacity, and formed fewer capillary-like networks. Intrajugular administration of human cord blood–derived ECFCs after established arrested alveolar growth restored lung function, alveolar and lung vascular growth, and attenuated pulmonary hypertension. Lung ECFC colony- and capillary-like network-forming capabilities were also restored. Low ECFC engraftment and the protective effect of cell-free ECFC-derived conditioned media suggest a paracrine effect. Long-term (10 months) assessment of ECFC therapy showed no adverse effects with persistent improvement in lung structure, exercise capacity, and pulmonary hypertension. Conclusions Impaired ECFC function may contribute to arrested alveolar growth. Cord blood–derived ECFC therapy may offer new therapeutic options for lung diseases characterized by alveolar damage. PMID:24710033

  2. Reformulation of DFT +U as a Pseudohybrid Hubbard Density Functional for Accelerated Materials Discovery

    NASA Astrophysics Data System (ADS)

    Agapito, Luis A.; Curtarolo, Stefano; Buongiorno Nardelli, Marco

    2015-01-01

    The accurate prediction of the electronic properties of materials at a low computational expense is a necessary condition for the development of effective high-throughput quantum-mechanics (HTQM) frameworks for accelerated materials discovery. HTQM infrastructures rely on the predictive capability of density functional theory (DFT), the method of choice for the first-principles study of materials properties. However, DFT suffers from approximations that result in a somewhat inaccurate description of the electronic band structure of semiconductors and insulators. In this article, we introduce ACBN0, a pseudohybrid Hubbard density functional that yields an improved prediction of the band structure of insulators such as transition-metal oxides, as shown for TiO2 , MnO, NiO, and ZnO, with only a negligible increase in computational cost.

  3. Accelerating the two-point and three-point galaxy correlation functions using Fourier transforms

    NASA Astrophysics Data System (ADS)

    Slepian, Zachary; Eisenstein, Daniel J.

    2016-01-01

    Though Fourier transforms (FTs) are a common technique for finding correlation functions, they are not typically used in computations of the anisotropy of the two-point correlation function (2PCF) about the line of sight in wide-angle surveys because the line-of-sight direction is not constant on the Cartesian grid. Here we show how FTs can be used to compute the multipole moments of the anisotropic 2PCF. We also show how FTs can be used to accelerate the 3PCF algorithm of Slepian & Eisenstein. In both cases, these FT methods allow one to avoid the computational cost of pair counting, which scales as the square of the number density of objects in the survey. With the upcoming large data sets of Dark Energy Spectroscopic Instrument, Euclid, and Large Synoptic Survey Telescope, FT techniques will therefore offer an important complement to simple pair or triplet counts.

  4. Impact of Endoscopic Lung Volume Reduction on Right Ventricular Myocardial Function

    PubMed Central

    Pizarro, Carmen; Schueler, Robert; Hammerstingl, Christoph; Tuleta, Izabela; Nickenig, Georg; Skowasch, Dirk

    2015-01-01

    Introduction Endoscopic lung volume reduction (ELVR) provides a minimally invasive therapy for patients with severe lung emphysema. As its impact on right ventricular (RtV) function is undefined, we examined the extent of RtV functional changes following ELVR, as assessed by use of speckle tracking-based RtV deformation analysis. Methods We enrolled 32 patients with severe emphysematous COPD scheduled for bronchoscopic LVR using endobronchial valves (Zephyr, PulmonX, Inc.), comprising 16 matched clinical responders and 16 non-responders. Echocardiography was conducted one day prior to ELVR and at an eight-week postprocedural interval. Results Patients were predominantly of late middle-age (65.8±8.7yrs), male (62.5%) and presented advanced COPD emphysema (means FEV1 and RV: 32.6% and 239.1% of predicted, respectively). After ELVR, RtV apical longitudinal strain improved significantly in the total study cohort (-7.96±7.02% vs. -13.35±11.48%, p=0.04), whereas there were no significant changes in other parameters of RtV function such as RtV global longitudinal strain, TAPSE or pulmonary arterial systolic pressure. In responding patients, 6MWT-improvement correlated with a decrease in NT-proBNP (Pearson´s r: -0.53, p=0.03). However, clinical non-responders did not exhibit any RtV functional improvement. Discussion ELVR beneficially impacts RtV functional parameters. Speckle tracking-based RtV apical longitudinal strain analysis allows early determination of RtV contractile gain and identification of clinical responsiveness. PMID:25856379

  5. 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.

  6. 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

  7. 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.

  8. 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. PMID:26493801

  9. 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

  10. The loss of Hoxa5 function promotes Notch-dependent goblet cell metaplasia in lung airways

    PubMed Central

    Boucherat, Olivier; Chakir, Jamila; Jeannotte, Lucie

    2012-01-01

    Summary Hox genes encode transcription factors controlling complex developmental processes in various organs. Little is known, however, about how HOX proteins control cell fate. Herein, we demonstrate that the goblet cell metaplasia observed in lung airways from Hoxa5−/− mice originates from the transdifferentiation of Clara cells. Reduced CC10 expression in Hoxa5−/− embryos indicates that altered cell specification occurs prior to birth. The loss of Hoxa5 function does not preclude airway repair after naphthalene exposure, but the regenerated epithelium presents goblet cell metaplasia and less CC10-positive cells, demonstrating the essential role of Hoxa5 for correct differentiation. Goblet cell metaplasia in Hoxa5−/− mice is a FOXA2-independent process. However, it is associated with increased Notch signaling activity. Consistent with these findings, expression levels of activated NOTCH1 and the effector gene HEY2 are enhanced in patients with chronic obstructive pulmonary disease. In vivo administration of a γ-secretase inhibitor attenuates goblet cell metaplasia in Hoxa5−/− mice, highlighting the contribution of Notch signaling to the phenotype and suggesting a potential therapeutic strategy to inhibit goblet cell differentiation and mucus overproduction in airway diseases. In summary, the loss of Hoxa5 function in lung mesenchyme impacts on epithelial cell fate by modulating Notch signaling. PMID:23213461

  11. About the effect of pulmonary rehabilitation on lung function in patients with chronic obstructive pulmonary disease.

    PubMed

    Incorvaia, Cristoforo; Riario-Sforza, Gian-Galeazzo; Ridolo, Erminia

    2016-01-01

    Detecting an improvement of lung function in a patient with chronic obstructive pulmonary disease (COPD) following pulmonary rehabilitation (PR) may appear unexpected, but actually recent studies showed that is not so rare. In fact, in a prospective study comparing a group of 190 COPD patients undergoing PR to a group of 67 patients treated only with drugs a mean improvement of FEV1 from 1240 mL to 1252.4 mL was found in the former, while the values changed from 1367 mL to 1150 mL in the latter (p < 0.001). Such improvement was detected also in a study in patients with very severe COPD, as assessed by a FEV1 increasing from 970 mL at baseline to 1080 mL after a 3-week PR inpatient program (p < 0.001). These observations suggest that improvement of lung function in COPD patients undergoing PR should be included among the expected outcomes and routinely assessed as an index of clinical success during the treatment. PMID:27489761

  12. 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

  13. Nicotinic acetylcholine receptor expression in human airway correlates with lung function.

    PubMed

    Lam, David Chi-Leung; Luo, Susan Yang; Fu, Kin-Hang; Lui, Macy Mei-Sze; Chan, Koon-Ho; Wistuba, Ignacio Ivans; Gao, Boning; Tsao, Sai-Wah; Ip, Mary Sau-Man; Minna, John Dorrance

    2016-02-01

    Nicotine and its derivatives, by binding to nicotinic acetylcholine receptors (nAChRs) on bronchial epithelial cells, can regulate cellular signaling and inflammatory processes. Delineation of nAChR subtypes and their responses to nicotine stimulation in bronchial epithelium may provide information for therapeutic targeting in smoking-related inflammation in the airway. Expression of nAChR subunit genes in 60 bronchial epithelial biopsies and immunohistochemical staining for the subcellular locations of nAChR subunit expression were evaluated. Seven human bronchial epithelial cell lines (HBECs) were exposed to nicotine in vitro for their response in nAChR subunit gene expression to nicotine exposure and removal. The relative normalized amount of expression of nAChR α4, α5, and α7 and immunohistochemical staining intensity of nAChR α4, α5, and β3 expression showed significant correlation with lung function parameters. Nicotine stimulation in HBECs resulted in transient increase in the levels of nAChR α5 and α6 but more sustained increase in nAChR α7 expression. nAChR expression in bronchial epithelium was found to correlate with lung function. Nicotine exposure in HBECs resulted in both short and longer term responses in nAChR subunit gene expression. These results gave insight into the potential of targeting nAChRs for therapy in smoking-related inflammation in the airway. PMID:26608528

  14. 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.

  15. Muscle mass, structural and functional investigations of senescence-accelerated mouse P8 (SAMP8)

    PubMed Central

    Guo, An Yun; Leung, Kwok Sui; Siu, Parco Ming Fai; Qin, Jiang Hui; Chow, Simon Kwoon Ho; Qin, Ling; Li, Chi Yu; Cheung, Wing Hoi

    2015-01-01

    Sarcopenia is an age-related systemic syndrome with progressive deterioration in skeletal muscle functions and loss in mass. Although the senescence-accelerated mouse P8 (SAMP8) was reported valid for muscular ageing research, there was no report on the details such as sarcopenia onset time. Therefore, this study was to investigate the change of muscle mass, structure and functions during the development of sarcopenia. Besides the average life span, muscle mass, structural and functional measurements were also studied. Male SAMP8 animals were examined at month 6, 7, 8, 9, and 10, in which the right gastrocnemius was isolated and tested for ex vivo contractile properties and fatigability while the contralateral one was harvested for muscle fiber cross-sectional area (FCSA) and typing assessments. Results showed that the peak of muscle mass appeared at month 7 and the onset of contractility decline was observed from month 8. Compared with month 8, most of the functional parameters at month 10 decreased significantly. Structurally, muscle fiber type IIA made up the largest proportion of the gastrocnemius, and the fiber size was found to peak at month 8. Based on the altered muscle mass, structural and functional outcomes, it was concluded that the onset of sarcopenia in SAMP8 animals was at month 8. SAMP8 animals at month 8 should be at pre-sarcopenia stage while month 10 at sarcopenia stage. It is confirmed that SAMP8 mouse can be used in sarcopenia research with established time line in this study. PMID:26193895

  16. Quantification of the Relative Contribution of Environmental and Genetic Factors to Variation in Cystic Fibrosis Lung Function

    PubMed Central

    Collaco, J. Michael; Blackman, Scott M.; McGready, John; Naughton, Kathleen M.; Cutting, Garry R.

    2010-01-01

    Objective To assess the relative contributions of environmental and genetic factors to variation in cystic fibrosis (CF) pulmonary disease. Study design Genetic and environmental contributions were quantified using intra-pair correlations and differences in CF-specific FEV1 measures from 134 monozygous twins and 272 dizygous twins and siblings while in different living environments (i.e. living with parents vs. living alone) as well as using intra-individual differences in lung function from a separate group of 80 siblings. Results Lung function among monozygous twins was more similar than among dizygous twin and sibling pairs, regardless of living environment, affirming the role of genetic modifiers in CF lung function. Regression modeling revealed that genetic factors account for 50% of lung function variation, unique environmental and stochastic factors 36%, and shared environmental factors, 14% (Model p: <0.0001). The intra-individual analysis produced similar estimates for the contributions of the unique and shared environment. The shared environment effects appeared primarily due to living with a sibling with CF (p: 0.003), rather than factors within the parental household (p: 0.310). Conclusions Genetic and environmental factors contribute equally to lung function variation in CF. Environmental effects are dominated by unique and stochastic effects rather than common exposures. PMID:20580019

  17. Occupational Health Hazards among Sewage Workers: Oxidative Stress and Deranged Lung Functions

    PubMed Central

    Agrawal, Dhirendra Kumar; Aslam, Mohammad; Islam, Najmul; Ahmad, Zuber

    2014-01-01

    Background: Sewage workers, because of their occupation, are exposed to different types of dusts, bio-aerosols, fumes and gases like methane, hydrogen sulfide, sulphur dioxide, etc, which contribute towards oxidative stress and detrimental effects on various body functions, especially lung functions. Aims and Objectives: This study was carried out on sewage workers (who had been working for more than five years). We wanted to study the role of oxidative stress in development of impaired lung functions among sewage workers. Materials and Methods: This cross sectional study was done in a tertiary care hospital (J.N. Medical College) in Aligarh, U.P. Study was done from March 2008 to December 2009. The study group comprised of 62 sewage workers who had been working for more than five years (32 non-smokers and 30 smokers) and 60 control subjects (30 smokers and 30 non-smokers). The pulmonary functions of these workers were assessed by using a MIR (Medical International Lab) Spiro Lab II Spirometer, with subjects in sitting position. Valid written consents were obtained from all the subjects. Malondialdehyde (MDA) is produced as a result of the action of reactive oxygen species (ROS) on the lipids present in the membranes of the cells, especially, contracting muscle cells. Serum MDA levels were assessed as an indirect measure of oxidative stress in these sewage workers and they were compared with serum MDA levels of control subjects. Appropriate statistical tests were applied for analysis of the data which was generated. Observation and Results: There were statistically significant decreases in Peak Expiratory Flow Rate (PEFR), Forced Expiratory Volume in first second (FEV1) and FEV1/FVC percent ratio (<80%) and Forced Expiratory Flow at 25%-75% of volume as percentage of Vital Capacity (FEF 25%-75%). Also, we found statistically significant increased levels of serum MDA in these sewage workers as compared to those in control subjects (with a p-value of <0.05 with a

  18. 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.

  19. 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

  20. Functionality, growth and accelerated aging of tissue engineered living autologous vascular grafts.

    PubMed

    Kelm, Jens M; Emmert, Maximilian Y; Zürcher, Armin; Schmidt, Dörthe; Begus Nahrmann, Yvonne; Rudolph, Karl L; Weber, Benedikt; Brokopp, Chad E; Frauenfelder, Thomas; Leschka, Sebastian; Odermatt, Bernhard; Jenni, Rolf; Falk, Volkmar; Zünd, Gregor; Hoerstrup, Simon P

    2012-11-01

    Living autologous tissue engineered vascular-grafts (TEVGs) with growth-capacity may overcome the limitations of contemporary artificial-prostheses. However, the multi-step in vitro production of TEVGs requires extensive ex vivo cell-manipulations with unknown effects on functionality and quality of TEVGs due to an accelerated biological age of the cells. Here, the impact of biological cell-age and tissue-remodeling capacity of TEVGs in relation to their clinical long-term functionality are investigated. TEVGs were implanted as pulmonary-artery (PA) replacements in juvenile sheep and followed for up to 240 weeks (∼4.5years). Telomere length and telomerase activity were compared amongst TEVGs and adjacent native tissue. Telomerase-activity of in vitro expanded autologous vascular-cells prior to seeding was <5% as compared to a leukemic cell line, indicating biological-aging associated with decreasing telomere-length with each cellular-doubling. Up to 100 weeks, the cells in the TEVGs had consistently shorter telomeres compared to the native counterpart, whereas no significant differences were detectable at 240 weeks. Computed tomography (CT) analysis demonstrated physiological wall-pressures, shear-stresses, and flow-pattern comparable to the native PA. There were no signs of degeneration detectable and continuous native-analogous growth was confirmed by vessel-volumetry. TEVGs exhibit a higher biological age compared to their native counterparts. However, despite of this tissue engineering technology related accelerated biological-aging, growth-capacity and long-term functionality was not compromised. To the contrary, extensive in-vivo remodeling processes with substantial endogenous cellular turnover appears to result in "TEVG rejuvenation" and excellent clinical performance. As these large-animal results can be extrapolated to approximately 20 human years, this study suggests long-term clinical-safety of cardiovascular in vitro tissue engineering and may

  1. Echocardiographic evaluation of pulmonary venous blood flow and cardiac function changes during one-lung ventilation

    PubMed Central

    Lee, Su Hyun; Kim, Namo; Kim, Hyun IL; Oh, Young Jun

    2015-01-01

    Objectives: The intra-pulmonary shunt induced by one-lung ventilation (OLV), is alleviated by increased pulmonary blood flow by gravitational redistribution and hypoxic pulmonary vasoconstriction. We investigated the changes of pulmonary venous blood flow (PVBF) and biventricular function during OLV with echocardiography. And the correlation between PVBF and intra-pulmonary shunt fraction (Qs/Qt) was evaluated. Methods: PVBF of the left upper pulmonary vein and cardiac function were measured with echocardiography in twenty-five patients who underwent elective thoracic surgery in left lateral decubitus. Qs/Qt and PaO2 were measured with blood gas analysis. Data was obtained at 10 min after two-lung ventilation in supine (TLV-S) and lateral decubitus position (TLV-L), and at 10, 20 and 30 min after OLV in lateral decubitus position (OLV-10, -20 and -30). Results: There were significant changes in PVBF among TLV-S, TLV-L and OLV-10 (959.5±280.8, 1416.9±489.7 and 1999.9±670.5 ml/min; P<0.05, respectively). There were not differences in PVBF, Qs/Qt and PaO2 among OLV-10, -20 and -30. There were an inverse correlation between percent change of PVBF and change of Qs/Qt (r2 = 0.5; P<0.0001) and positive correlations between the percent change of PVBF and change of PaO2 (r2 = 0.4; P<0.0001) during OLV over TLV-L. No significant changes in biventricular systolic and diastolic function were observed during positional change and OLV. Conclusions: A remarkable change of PVBF relevant to gravitational distribution and hypoxic pulmonary vasoconstriction was proved by echocardiography. And PVBF changes could represent the changes of Qs/Qt and PaO2 during OLV. However, biventricular function was not impaired during OLV. PMID:26550232

  2. 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

  3. 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.

  4. Ginkgolide B functions as a determinant constituent of Ginkgolides in alleviating lipopolysaccharide-induced lung injury.

    PubMed

    Wu, Fugen; Shi, Wei; Zhou, Guojun; Yao, Hongyi; Xu, Chengyun; Xiao, Weiqiang; Wu, Junsong; Wu, Ximei

    2016-07-01

    Ginkgolides are the major bioactive components of Ginkgo biloba extracts, however, the exact constituents of Ginkgolides contributing to their pharmacological effects remain unknown. Herein, we have determined the anti-inflammatory effects of Ginkgolide B (GB) and Ginkgolides mixture (GM) at equivalent dosages against lipopolysaccharide (LPS)-induced inflammation. RAW 264.7 cell culture model and mouse model of LPS-induced lung injury were used to evaluate in vitro and in vivo effects of GB and GM, respectively. In RAW 264.7 cells, GB and GM at equivalent dosages exhibit an identical capacity to attenuate LPS-induced inducible nitric oxide synthase mRNA and protein expression and subsequent NO production. Likewise, GB and GM possess almost the same potency in attenuating LPS-induced expression and activation of nuclear factor kappa B (p65) and subsequent increases in tumor necrosis factor-α mRNA levels. In LPS-induced pulmonary injury, GB and GM at the equivalent dosages have equal efficiency in attenuating the accumulation of inflammatory cells, including neutrophils, lymphocytes, and macrophages, and in improving the histological damage of lungs. Moreover, GB and GM at equivalent dosages decrease the exudation of plasma protein to the same degree, whereas GM is superior to GB in alleviating myeloperoxidase activities. Finally, though GB and GM at equivalent dosages appear to reduce LPS-induced IL-1β mRNA and protein levels and IL-10 protein levels to the same degree, GM is more potent than GB to attenuate the IL-10 mRNA levels. Taken together, this study demonstrates that GB functions as the determinant constituent of Ginkgolides in alleviating LPS-induced lung injury. PMID:27261579

  5. Endogenous ligands of the aryl hydrocarbon receptor regulate lung dendritic cell function.

    PubMed

    Thatcher, Thomas H; Williams, Marc A; Pollock, Stephen J; McCarthy, Claire E; Lacy, Shannon H; Phipps, Richard P; Sime, Patricia J

    2016-01-01

    The aryl hydrocarbon receptor (AhR) is a transcription factor that has been extensively studied as a regulator of toxicant metabolism. However, recent evidence indicates that the AhR also plays an important role in immunity. We hypothesized that the AhR is a novel, immune regulator of T helper type 2 (Th2) -mediated allergic airway disease. Here, we report that AhR-deficient mice develop increased allergic responses to the model allergen ovalbumin (OVA), which are driven in part by increased dendritic cell (DC) functional activation. AhR knockout (AhR(-/-) ) mice sensitized and challenged with OVA develop an increased inflammatory response in the lung compared with wild-type controls, with greater numbers of inflammatory eosinophils and neutrophils, greater T-cell proliferation, greater production of Th2 cytokines, and higher levels of OVA-specific IgE and IgG1. Lung DCs from AhR(-/-) mice stimulated antigen-specific proliferation and Th2 cytokine production by naive T cells in vitro. Additionally, AhR(-/-) DCs produced higher levels of tumour necrosis factor-α and interleukin-6, which promote Th2 differentiation, and expressed higher cell surface levels of stimulatory MHC Class II and CD86 molecules. Overall, loss of the AhR was associated with enhanced T-cell activation by pulmonary DCs and heightened pro-inflammatory allergic responses. This suggests that endogenous AhR ligands are involved in the normal regulation of Th2-mediated immunity in the lung via a DC-dependent mechanism. Therefore, the AhR may represent an important target for therapeutic intervention in allergic airways inflammation.

  6. 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.

  7. 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%.

  8. 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%.

  9. 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.

  10. 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

  11. The relationship between lung function and indoor air pollution among rural women in the Niger Delta region of Nigeria

    PubMed Central

    Umoh, Victor Aniedi; Peters, Etete

    2014-01-01

    Background: Burning of biomass is widely used by the rural poor for energy generation. Long term exposure to biomass smoke is believed to affect lung function and cause respiratory symptoms. Materials and Methods: Women with long term occupational exposure to burning firewood were recruited from a rural fishing community in Nigeria. A questionnaire was used to obtain information on symptoms of chronic bronchitis and spirometery was performed to measure lung function. Data obtained from the subjects was compared with that from healthy controls. Results: Six hundred and eighty six women were recruited for this study made up of 342 subjects and 346 controls. Sixty eight (19.9%) of the subjects had chronic bronchitis compared with eight (2.3%) of the controls (χ2 = 54.0, P < 0.001). The subjects had lower values for the lung function as well as the percentage predicted values (P < 0.05). Fish smoking and chronic bronchitis were significantly associated with predicted lung volumes. Conclusion: Chronic exposure to biomass smoke is associated with chronic bronchitis and reduced lung functions in women engaged in fish smoking. PMID:24778471

  12. Expression of secretory phospholipase A2 enzymes in lungs of humans with pneumonia and their potential prostaglandin-synthetic function in human lung-derived cells

    PubMed Central

    Masuda, Seiko; Murakami, Makoto; Mitsuishi, Michiko; Komiyama, Kazuo; Ishikawa, Yukio; Ishii, Toshiharu; Kudo, Ichiro

    2004-01-01

    Although a number of sPLA2 (secretory phospholipase A2) enzymes have been identified in mammals, the localization and functions of individual enzymes in human pathologic tissues still remain obscure. In the present study, we have examined the expression and function of sPLA2s in human lung-derived cells and in human lungs with pneumonia. Group IID, V and X sPLA2s were expressed in cultured human bronchial epithelial cells (BEAS-2B) and normal human pulmonary fibroblasts with distinct requirement for cytokines (interleukin-1β, tumour necrosis factor α and interferon-γ). Lentivirus- or adenovirus-mediated transfection of various sPLA2s into BEAS-2B or normal human pulmonary fibroblast cells revealed that group V and X sPLA2s increased arachidonate release and prostaglandin production in both cell types, whereas group IIA and IID sPLA2s failed to do so. Immunohistochemistry of human lungs with pneumonia demonstrated that group V and X sPLA2s were widely expressed in the airway epithelium, interstitium and alveolar macrophages, in which group IID sPLA2 was also positive, whereas group IIA sPLA2 was restricted to the pulmonary arterial smooth muscle layers and bronchial chondrocytes, and group IIE and IIF sPLA2s were minimally detected. These results suggest that group V and X sPLA2s affect lung pathogenesis by facilitating arachidonate metabolism or possibly through other functions. PMID:15509193

  13. 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

  14. 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

  15. Liquid ventilation improves pulmonary function, gas exchange, and lung injury in a model of respiratory failure.

    PubMed Central

    Hirschl, R B; Parent, A; Tooley, R; McCracken, M; Johnson, K; Shaffer, T H; Wolfson, M R; Bartlett, R H

    1995-01-01

    OBJECTIVE: The authors evaluated gas exchange, pulmonary function, and lung histology during perfluorocarbon liquid ventilation (LV) when compared with gas ventilation (GV) in the setting of severe respiratory failure. BACKGROUND: The efficacy of LV in the setting of respiratory failure has been evaluated in premature animals with surfactant deficiency. However, very little work has been performed in evaluating the efficacy of LV in older animal models of the adult respiratory distress syndrome (ARDS). METHODS: A stable model of lung injury was induced in 12 young sheep weighing 16.4 +/- 3.0 kg using right atrial injection of 0.07 mL/kg of oleic acid followed by saline pulmonary lavage and bijugular venovenous extracorporeal life support (ECLS). For the first 30 minutes on ECLS, all animals were ventilated with gas. Animals were then ventilated with either 15 mL/kg gas (GV, n = 6) or perflubron ([PFC], LV, n = 6) over the ensuing 2.5 hours. Subsequently, ECLS was discontinued in five of the GV animals and five of the LV animals, and GV or LV continued for 1 hour or until death. MAIN FINDINGS: Physiologic shunt (Qps/Qt) was significantly reduced in the LV animals when compared with the GV animals (LV = 31 +/- 10%; GV = 93 +/- 4%; p < 0.001) after 3 hours of ECLS. At the same time point, pulmonary compliance (CT) was significantly increased in the LV group when compared with the GV group (LV = 1.04 +/- 0.19 mL/cm H2O/kg; GV = 0.41 +/- 0.02 mL/cm H2O/kg; p < 0.001). In addition, the ECLS flow rate required to maintain the PaO2 in the 50- to 80-mm Hg range was substantially and significantly lower in the LV group when compared with that of the GV group (LV = 14 +/- 5 mL/kg/min; GV = 87 +/- 15 mL/kg/min; p < 0.001). All of the GV animals died after discontinuation of ECLS, whereas all the LV animals demonstrated effective gas exchange without extracorporeal support for 1 hour (p < 0.01). Lung biopsy light microscopy demonstrated a marked reduction in alveolar hemorrhage

  16. 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.

  17. 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.

  18. Pulmonary function tests in the preoperative evaluation of lung cancer surgery candidates. A review of guidelines

    PubMed Central

    Skoczyński, Szymon; Pierzchała, Władysław

    2014-01-01

    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). PMID:26336435

  19. 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.

  20. 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

  1. Viral bronchiolitis in young rats causes small airway lesions that correlate with reduced lung function.

    PubMed

    Sorkness, Ronald L; Szakaly, Renee J; Rosenthal, Louis A; Sullivan, Ruth; Gern, James E; Lemanske, Robert F; Sun, Xin

    2013-11-01

    Viral illness with wheezing during infancy is associated with the inception of childhood asthma. Small airway dysfunction is a component of childhood asthma, but little is known about how viral illness at an early age may affect the structure and function of small airways. We used a well-characterized rat model of postbronchiolitis chronic airway dysfunction to address how postinfectious small airway lesions affect airway physiological function and if the structure/function correlates persist into maturity. Brown Norway rats were sham- or virus inoculated at 3 to 4 weeks of age and allowed to recover from the acute illness. At 3 to 14 months of age, physiology (respiratory system resistance, Newtonian resistance, tissue damping, and static lung volumes) was assessed in anesthetized, intubated rats. Serial lung sections revealed lesions in the terminal bronchioles that reduced luminal area and interrupted further branching, affecting 26% (range, 13-39%) of the small airways at 3 months of age and 22% (range, 6-40%) at 12 to 14 months of age. At 3 months of age (n = 29 virus; n = 7 sham), small airway lesions correlated with tissue damping (rs = 0.69) but not with Newtonian resistance (rs = 0.23), and Newtonian resistance was not elevated compared with control rats, indicating that distal airways were primarily responsible for the airflow obstruction. Older rats (n = 7 virus; n = 6 sham) had persistent small airway dysfunction and significantly increased Newtonian resistance in the postbronchiolitis group. We conclude that viral airway injury at an early age may induce small airway lesions that are associated quantitatively with small airway physiological dysfunction early on and that these defects persist into maturity.

  2. 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

  3. 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

    2016-01-01

    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

  4. Effects of a single saturation dive on lung function and exercise performance.

    PubMed

    Lehnigk, B; Jörres, R A; Elliott, D H; Holthaus, J; Magnussen, H

    1997-01-01

    We studied the effects of an experimental saturation dive to 360 and 450 m in a simulation chamber on spirometric lung function, diffusing capacity, pulmonary compliance, and exercise performance in eight professional divers (age 22-40 years). To assess intraindividual variability, all parameters were measured on 2 days before and on 2 consecutive days immediately after the dive. For the group as a whole there was a significant increase in vital capacity and alveolar volume, and a decrease in Krogh factor and specific compliance (P < 0.01). These changes were reduced on the 2nd day after the dive. All subjects showed lowered exercise performance after the dive. Arterial pressure of oxygen and ventilation during exercise increased (P < 0.01), whereas arterial pressure of carbon dioxide, oxygen uptake, and anaerobic threshold decreased (P < 0.01). Exercise parameters showed only a slight trend towards pre-dive values on the 2nd day after a dive. The individual analysis revealed that after the dive two subjects showed a marked decrease in diffusing capacity and a more than average decrease in Krogh factor (TLCO/VA). One of them had signs of mild decompression sickness and the other, signs of pre-existing obstructive airways disease. Our data are compatible with the hypothesis that the effects of a single deep saturation dive on pulmonary function and exercise performance are the results of counteracting mechanisms. We suggest that lung volumes increase due to the enhanced work of breathing during a deep saturation dive and that these changes could mask an impairment in gas exchange. Furthermore, a saturation dive can induce an apparent deterioration of pulmonary function.

  5. 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

  6. 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.

  7. 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

  8. Maternal smoking during pregnancy, environmental tobacco smoke exposure and childhood lung function

    PubMed Central

    Gilliland, F.; Berhane, K.; McConnell, R.; Gauderman, W; Vora, H.; Rappaport, E.; Avol, E.; Peters, J.

    2000-01-01

    BACKGROUND—Exposure to environmental tobacco smoke (ETS) during childhood and in utero exposure to maternal smoking are associated with adverse effects on lung growth and development.
METHODS—A study was undertaken of the associations between maternal smoking during pregnancy, exposure to ETS, and pulmonary function in 3357 school children residing in 12 Southern California communities. Current and past exposure to household ETS and exposure to maternal smoking in utero were assessed by a self-administered questionnaire completed by parents of 4th, 7th, and 10th grade students in 1993.Standard linear regression techniques were used to estimate the effects of in utero and ETS exposure on lung function, adjusting for age, sex, race, Hispanic ethnicity, height, weight, asthma, personal smoking, and selected household characteristics.
RESULTS—In utero exposure to maternal smoking was associated with reduced peak expiratory flow rate (PEFR) (-3.0%, 95% CI -4.4 to -1.4), mean mid expiratory flow (MMEF) (-4.6%, 95% CI -7.0 to -2.3), and forced expiratory flow (FEF75) (-6.2%, 95% CI -9.1 to -3.1), but not forced expiratory volume in one second (FEV1). Adjusting for household ETS exposure did not substantially change these estimates. The reductions in flows associated with in utero exposure did not significantly vary with sex, race, grade, income, parental education, or personal smoking. Exposure to two or more current household smokers was associated with reduced MMEF (-4.1%, 95% CI -7.6 to -0.4) and FEF75 (-4.4%, 95% CI -9.0 to 0.4). Current or past maternal smoking was associated with reductions in PEFR and MMEF; however, after adjustment for in utero exposure, deficits in MMEF and FEF75 associated with all measurements of ETS were substantially reduced and were not statistically significant.
CONCLUSIONS—In utero exposure to maternal smoking is independently associated with decreased lung function in children of school age, especially for small airway flows

  9. [Differential diagnosis of chronic obstructive lung disease, A statistical analysis of the discriminating power of various lung function tests (author's transl)].

    PubMed

    Delaunois, L; Lulling, J; Prignot, J

    1976-01-01

    Among 65 patients admitted to the hospital for chronic obstructive lung disease, the following pulmonary tests were systematically performed : spirometric vital capacity and total lung capacity, FEV1, functional residual capacity and total lung capacity measured by body plethysmography, airway resistance and specific conductance, CO diffusion capacity measured by single-breath test, N2 clearance by single breath oxygen dilution, and blood gases. The patients were divided into bronchitics, emphysematous and broncho-emphysematous, according to the clinical and radiological Nash's score, and to another personal score derived from the former. The simple and multiple correlations between the clinico-radiological score and the functional results are low. The clustering analysis groups the 65 patients into four clouds of points, around two principal axes : the volume axis and the overinflation axis. This study indicates that the most suggestive results for emphysema diagnosis are increased FRC and TLC and low Tlco/V'a. The clinical score is not dominant for the clustering of the patients into the dynamic clouds. Beneath the bronchitic, the broncho-emphysematous and the emphysematous groups, the clustering analysis individualizes a fourth group of cases characterized by chronic asthma, and which were not isolated by Nash's score.

  10. 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.

  11. Long-term benefits in lung function and nutritional status of strict metabolic control of cystic fibrosis-related diabetes.

    PubMed

    Martín-Frías, María; Máiz, Luis; Carcavilla, Atilano; Barrio, Raquel

    2011-10-01

    Cystic fibrosis related diabetes (CFRD) is a strong determinant for lung function decline and increased mortality. Insulin treatment of CFRD is reportedly beneficial for this situation. We report on the long-term impact of insulin treatment of CFRD on pulmonary function and nutritional status in a CF male patient since diagnosis of diabetes. We report the case of a patient diagnosed with CF at the age of 16. Two years later, he experienced a rapidly evolving decrease in pulmonary function, some months later criteria were met warranting lung transplantation. Concomitantly, he was diagnosed with CFRD and insulin therapy was started. Lung function (spirometry), nutritional status (body mass index) and metabolic control (HbA(1c)) were determined every 3 months. After the introduction of insulin treatment, pulmonary function and nutritional status progressively improved and good glycemic control was achieved. The significant and sustained improvement in pulmonary function allowed for the patient's withdrawal from the lung transplantation program within 4 months, a situation which has been maintained until now, 8 years later. The long follow-up of our patient documents the rapid and prolonged beneficial effect of proper metabolic control of CFRD on the respiratory deterioration in CF.

  12. Nonrespiratory metabolic function and morphology of lung following exposure to polybrominated biphenyls in rats

    SciTech Connect

    McCormack, K.M.; Roth, R.A.; Wallace, K.B.; Ross, L.M.; Hook, J.B.

    1982-01-01

    Exposure to polybrominated biphenyls (PBBs) resulted in increased activity of microsomal arylhydrocarbon hydroxylase and ethoxyresorufin-O-deethylase in rat lung. Clearance of 5-hydroxytryptamine (5-HT) and angiotensin I by perfused lungs was decreased by PBBs. However, PBBs had no effect on the activity of epoxide hydrolase, monoamine oxidase, or angiotensin-converting enzyme in lung. The only hisotpathlogic change detected in lungs from PBB-treated rats was an increase in alveolar type II cell lamellar bodies. Selective accumulation of certain PBB congeners by lung was not observed in this investigation.

  13. Large-Scale Genome-Wide Association Studies and Meta-Analyses of Longitudinal Change in Adult Lung Function

    PubMed Central

    Tang, Wenbo; Kowgier, Matthew; Loth, Daan W.; Soler Artigas, María; Joubert, Bonnie R.; Hodge, Emily; Gharib, Sina A.; Smith, Albert V.; Ruczinski, Ingo; Gudnason, Vilmundur; Mathias, Rasika A.; Harris, Tamara B.; Hansel, Nadia N.; Launer, Lenore J.; Barnes, Kathleen C.; Hansen, Joyanna G.; Albrecht, Eva; Aldrich, Melinda C.; Allerhand, Michael; Barr, R. Graham; Brusselle, Guy G.; Couper, David J.; Curjuric, Ivan; Davies, Gail; Deary, Ian J.; Dupuis, Josée; Fall, Tove; Foy, Millennia; Franceschini, Nora; Gao, Wei; Gläser, Sven; Gu, Xiangjun; Hancock, Dana B.; Heinrich, Joachim; Hofman, Albert; Imboden, Medea; Ingelsson, Erik; James, Alan; Karrasch, Stefan; Koch, Beate; Kritchevsky, Stephen B.; Kumar, Ashish; Lahousse, Lies; Li, Guo; Lind, Lars; Lindgren, Cecilia; Liu, Yongmei; Lohman, Kurt; Lumley, Thomas; McArdle, Wendy L.; Meibohm, Bernd; Morris, Andrew P.; Morrison, Alanna C.; Musk, Bill; North, Kari E.; Palmer, Lyle J.; Probst-Hensch, Nicole M.; Psaty, Bruce M.; Rivadeneira, Fernando; Rotter, Jerome I.; Schulz, Holger; Smith, Lewis J.; Sood, Akshay; Starr, John M.; Strachan, David P.; Teumer, Alexander; Uitterlinden, André G.; Völzke, Henry; Voorman, Arend; Wain, Louise V.; Wells, Martin T.; Wilk, Jemma B.; Williams, O. Dale; Heckbert, Susan R.; Stricker, Bruno H.; London, Stephanie J.; Fornage, Myriam; Tobin, Martin D.; O′Connor, George T.; Hall, Ian P.; Cassano, Patricia A.

    2014-01-01

    Background Genome-wide association studies (GWAS) have identified numerous loci influencing cross-sectional lung function, but less is known about genes influencing longitudinal change in lung function. Methods We performed GWAS of the rate of change in forced expiratory volume in the first second (FEV1) in 14 longitudinal, population-based cohort studies comprising 27,249 adults of European ancestry using linear mixed effects model and combined cohort-specific results using fixed effect meta-analysis to identify novel genetic loci associated with longitudinal change in lung function. Gene expression analyses were subsequently performed for identified genetic loci. As a secondary aim, we estimated the mean rate of decline in FEV1 by smoking pattern, irrespective of genotypes, across these 14 studies using meta-analysis. Results The overall meta-analysis produced suggestive evidence for association at the novel IL16/STARD5/TMC3 locus on chromosome 15 (P  =  5.71 × 10-7). In addition, meta-analysis using the five cohorts with ≥3 FEV1 measurements per participant identified the novel ME3 locus on chromosome 11 (P  =  2.18 × 10-8) at genome-wide significance. Neither locus was associated with FEV1 decline in two additional cohort studies. We confirmed gene expression of IL16, STARD5, and ME3 in multiple lung tissues. Publicly available microarray data confirmed differential expression of all three genes in lung samples from COPD patients compared with controls. Irrespective of genotypes, the combined estimate for FEV1 decline was 26.9, 29.2 and 35.7 mL/year in never, former, and persistent smokers, respectively. Conclusions In this large-scale GWAS, we identified two novel genetic loci in association with the rate of change in FEV1 that harbor candidate genes with biologically plausible functional links to lung function. PMID:24983941

  14. Electrical stimulation accelerates axonal and functional peripheral nerve regeneration across long gaps.

    PubMed

    Haastert-Talini, Kirsten; Schmitte, Ruth; Korte, Nele; Klode, Dorothee; Ratzka, Andreas; Grothe, Claudia

    2011-04-01

    Short-term low-frequency electrical stimulation (ESTIM) of proximal peripheral nerve stumps prior to end-to-end coaptation or tubular bridging of small distances has been reported to increase preferential motor reinnervation and functional motor recovery in animal models and human patients undergoing carpal tunnel release surgery. We investigated the effects of ESTIM on regeneration across rat sciatic nerve gaps, which exceed distances that allow spontaneous regeneration. Three different reconstruction approaches were combined with ESTIM in the experimental groups. Nerve gaps (13 mm) were bridged using (I) nerve autotransplantation, (II) transplantation of differentially filled silicone tubes, or (III) transplantation of tubular grafts containing fibroblast growth factor-2 overexpressing Schwann cells (SCs) for gene therapy. The regeneration outcome was followed for up to 8 weeks, and functionally as well as histomorphometrically analyzed in comparison to non-stimulated control groups. Combining ESTIM with nerve autotransplantation significantly increased the nerve fiber density in the regenerated nerve, and the grade of functional recovery as detected by electrodiagnostic recordings from the gastrocnemius muscle. The combination of ESTIM with transplantation of naïve SCs increased the regeneration of gap-bridging nerve tissue. Although macroscopic tissue regeneration was not further improved after combining ESTIM with FGF-2(21/23-kD) gene therapy, the latter resulted in a high rate of regenerated nerves that functionally reconnected to the target muscle. Based on our results, brief ESTIM shows high potential to accelerate axonal as well as functional (motor and sensory) outcomes in the clinical setting of peripheral nerve gap reconstruction in human patients. PMID:21265597

  15. Changes in lung function of children after an air pollution decrease

    SciTech Connect

    Arossa, W.; Spinaci, S.; Bugiani, M.; Natale, P.; Bucca, C.; de Candussio, G.

    1987-05-01

    Forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1.0), forced expiratory flow between 25 and 75% of FVC (FEF25-75), and maximal expiratory flow at 50% of FVC (MEF50) were measured in 1,880 school children who lived in urban areas before and after a decrease of air pollution. A group of 162 children from a suburban area served as controls. In the first survey, FEV1.0, FEF25-75, and MEF50 of children from urban areas were significantly lower, while in the second survey they were not significantly different from those of controls. The slopes over time of FEV1.0, FEF25-75, and MEF50, adjusted for sex and anthropometric variables, were closely related to the decrease of pollutants concentration. Our results suggest that a decrease of air pollution may produce an improvement of lung function.

  16. 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.

  17. Sixteen new lung function signals identified through 1000 Genomes Project reference panel imputation

    PubMed Central

    Artigas, María Soler; 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.; Deloukas, Panos; Hansell, Anna L.; Hubbard, Richard; Jackson, Victoria E.; Marchini, Jonathan; Pavord, Ian; Thomson, Neil C.; Zeggini, Eleftheria; 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.

    2015-01-01

    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. PMID:26635082

  18. 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

    2015-01-01

    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. PMID:26635082

  19. 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

  20. Effects of smoking on chest expansion, lung function, and respiratory muscle strength of youths.

    PubMed

    Tantisuwat, Anong; Thaveeratitham, Premtip

    2014-02-01

    [Purpose] Smoking has a direct effect on the respiratory system. The rate of cigarette smoking among young people has continued to increase steadily. The present study quantified and compared the respiratory function of smoking and non-smoking youths. [Subjects] Smoking and non-smoking male participants aged between 15 to 18 years were recruited (n=34 per group). [Methods] Participants were asked to complete a questionnaire relating to smoking habits and the Fagerström test for nicotine dependence questionnaire, and their respiratory function was tested (measurement of chest expansion, lung function test with a spirometer, and assessment of respiratory muscle strength). [Results] All respiratory function tests demonstrated significant differences between the smoking and non-smoking groups. Smokers initiated cigarette smoking between the ages of 15 to 18 years. The most common duration of cigarette smoking was 1-3 years and the degree of nicotine dependence among the youths was at a low level. [Conclusion] This study's findings show that the early effects of cigarette smoking found in youths can lead to problems with the respiratory system. Such information can be used to illustrate the harm of smoking and should be used to encourage young people to quit or avoid cigarette smoking. PMID:24648624

  1. Effects of Smoking on Chest Expansion, Lung Function, and Respiratory Muscle Strength of Youths

    PubMed Central

    Tantisuwat, Anong; Thaveeratitham, Premtip

    2014-01-01

    [Purpose] Smoking has a direct effect on the respiratory system. The rate of cigarette smoking among young people has continued to increase steadily. The present study quantified and compared the respiratory function of smoking and non-smoking youths. [Subjects] Smoking and non-smoking male participants aged between 15 to 18 years were recruited (n=34 per group). [Methods] Participants were asked to complete a questionnaire relating to smoking habits and the Fagerström test for nicotine dependence questionnaire, and their respiratory function was tested (measurement of chest expansion, lung function test with a spirometer, and assessment of respiratory muscle strength). [Results] All respiratory function tests demonstrated significant differences between the smoking and non-smoking groups. Smokers initiated cigarette smoking between the ages of 15 to 18 years. The most common duration of cigarette smoking was 1-3 years and the degree of nicotine dependence among the youths was at a low level. [Conclusion] This study’s findings show that the early effects of cigarette smoking found in youths can lead to problems with the respiratory system. Such information can be used to illustrate the harm of smoking and should be used to encourage young people to quit or avoid cigarette smoking. PMID:24648624

  2. Lung function and respiratory symptoms in a randomized smoking cessation trial of electronic cigarettes.

    PubMed

    Cibella, Fabio; Campagna, Davide; Caponnetto, Pasquale; Amaradio, Maria Domenica; Caruso, Massimo; Russo, Cristina; Cockcroft, Donald W; Polosa, Riccardo

    2016-11-01

    Quitting smoking is the most important step smokers can take to improve their health. Nonetheless, there is little information on long-term improvements in lung function and/or respiratory symptoms after smoking cessation. Here we illustrate long-term changes in spirometric indices as well as in respiratory symptoms in smokers invited to quit or reduce their cigarette consumption by switching to electronic cigarettes (ECs). Prospective evaluation of cigarette consumption, spirometry and symptoms was performed in a 1-year randomized controlled trial of smokers receiving EC containing 2.4%, 1.8% or 0% nicotine. Spirometric data are presented on the basis of participants' pooled continuous smoking phenotype classification (Quitters, Reducers, Failures), whereas respiratory symptoms on the basis of their point prevalence-smoking phenotype. Smoking phenotype classification (Quitters, Reducers, Failures) had no significant effect on spirometric indices (FEV1, FVC and FEV1/FVC) with the exception of FEF25-75%, which significantly (P  =0.034) increased over the time among Quitters; their FEF25-75% (% predicted) improving from (means±S.D.) 85.7±15.6% at baseline (BL) to 100.8±14.6%. High prevalence of cough/phlegm (43.1%) and shortness of breath (SoB; 34.8%) was reported at BL with substantial reduction in their frequency at subsequent follow-up visits. These symptoms virtually disappeared very quickly in both quitters and reducers. Smokers invited to switch to ECs who completely abstained from smoking showed steady progressive improvements in their FEF25-75% Normalization of peripheral airways function was associated with improvement in respiratory symptoms, adding to the notion that abstaining from smoking can reverse tobacco harm in the lung. PMID:27543458

  3. Does occupational exposure to brown coal dust cause a decline in lung function?

    PubMed Central

    Finocchiaro, C; Lark, A; Keating, M; Ugoni, A; Abramson, M

    1997-01-01

    OBJECTIVES: To determine if the rate of change in forced expiratory volume in one second (FEV1) in subjects with high exposure to Latrobe Valley brown coal dust was significantly greater than the rate of change among subjects with low exposure. METHODS: A retrospective dynamic cohort design with variable time windows. This study was conducted over a period of 14 years from 1980 to 1994 and used data collected by the State Electricity Commission (SEC) Lung Function Unit for an asbestos surveillance programme. The subjects were exposed to low, medium, or high levels of coal dust. Basic spirometry with wedge bellows spirometers was used to assess lung function. A general linear model (GLM) was used to assess the effects of smoking and exposure to coal dust upon the change in forced expiratory volume in one second (FEV1) while adjusting for age and height. RESULTS: The mean (95% confidence interval (95% CI) rate of decline in FEV1 was 40 (36 to 44) ml/year. Age was a significant predictor of change. A significant effect was found for smoking (P = 0.02) and for exposure to coal dust (P = 0.008). The only significant difference with exposure to coal dust was between the high and mixed exposure categories. CONCLUSION: There is no convincing evidence of excessive decline in FEV1 with exposure to coal dust > 0.75 mg/m3. The absence of a dose response relation provides some evidence against a causal relation. On the basis of this study, reduction of the exposure standards currently applied to brown coal dust in the Victorian electricity industry is not warranted to prevent respiratory disease. PMID:9423576

  4. Alteration in lung particle translocation, macrophage function, and microfilament arrangement in monocrotaline-treated rats.

    PubMed

    Madl, A K; Wilson, D W; Segall, H J; Pinkerton, K E

    1998-11-01

    Individuals with preexisting cardiopulmonary disease are thought to be more susceptible to acute episodes of particulate pollution resulting in increased morbidity and mortality. Our study was designed to evaluate particle fate and macrophage function in an animal model of monocrotaline (MCT)-induced pulmonary hypertension. Two weeks following a single MCT injection, Sprague-Dawley rats were exposed sequentially to two different colored fluorescent microspheres 1.0 micron in diameter by aerosolization. Morphometric evaluation of lung sections was performed 0 and 24 h following the final particle exposure to determine the intrapulmonary location of inhaled microspheres. A decrease in the number of particles phagocytized by alveolar macrophages and an increase of free particles overlying the epithelium were found in MCT-treated animals compared with control. Pulmonary macrophages recovered by bronchoalveolar lavage were evaluated for chemotactic and phagocytic ability. Macrophage chemotaxis was significantly impaired following MCT treatment compared with controls, whereas phagocytic activity of macrophages lavaged from MCT and control treatment groups was similar. Macrophages were stained for filamentous (F) and globular (G) actin using Texas-Red-labeled phalloidin and Oregon-green-labeled DNase I, respectively. The area of microfilament staining for F and G actin increased, but the ratio of F/G actin was significantly decreased in animals with MCT treatment compared with control. While the responses observed with MCT treatment, such as pulmonary edema, polymorphonuclear leukocytes influx, and unique macrophage morphology may contribute to impaired macrophage function, the change in microfilament arrangement suggests that MCT may inhibit macrophage chemotaxis and impair particle clearance from the lungs. PMID:9875297

  5. High-altitude alpine therapy and lung function in asthma: systematic review and meta-analysis

    PubMed Central

    Khafagy, Abdullah; Blanc, Paul D.; Brimkulov, Nurlan; Steinmaus, Craig

    2016-01-01

    We used meta-analysis to measure the effect of high-altitude climate therapy (HACT) on lung function outcomes in asthma, and systematically searched PubMed, Embase and www.elibrary.ru for publications appearing from 1970 to mid-2015. We included studies carried out with children or adults with an exposure of up to 12 weeks at an altitude of ≥1500 m above sea level. Changes in forced expiratory volume in 1 s (FEV1), FEV1/vital capacity ratio or peak expiratory flow rate as the HACT intervention outcomes were analysed. We included data for 907 participants (age range 4–58 years) from 21 studies, altogether including 28 substrata based on asthma type or severity. Only three of 21 included studies had high quality, whereas 93% of substudies reported lung function improvement with an overall pooled standardised mean difference (SMD) of 0.53 (95% CI 0.43–0.62). The measured effect of HACT was greater in adults (SMD 0.75, 95% CI 0.63–0.88, n=14) than in children (SMD 0.24, 95% CI 0.09–0.38, n=14). Studies at altitude >2000 m above sea level yielded the same effect as those at lower altitude. Based on a cut-point of a 0.50 change in SMD to define a meaningful clinical difference, HACT appears to have efficacy as an intervention. This extent of benefit appears to be limited to adults with asthma. PMID:27730196

  6. Lung function and respiratory symptoms in a randomized smoking cessation trial of electronic cigarettes.

    PubMed

    Cibella, Fabio; Campagna, Davide; Caponnetto, Pasquale; Amaradio, Maria Domenica; Caruso, Massimo; Russo, Cristina; Cockcroft, Donald W; Polosa, Riccardo

    2016-11-01

    Quitting smoking is the most important step smokers can take to improve their health. Nonetheless, there is little information on long-term improvements in lung function and/or respiratory symptoms after smoking cessation. Here we illustrate long-term changes in spirometric indices as well as in respiratory symptoms in smokers invited to quit or reduce their cigarette consumption by switching to electronic cigarettes (ECs). Prospective evaluation of cigarette consumption, spirometry and symptoms was performed in a 1-year randomized controlled trial of smokers receiving EC containing 2.4%, 1.8% or 0% nicotine. Spirometric data are presented on the basis of participants' pooled continuous smoking phenotype classification (Quitters, Reducers, Failures), whereas respiratory symptoms on the basis of their point prevalence-smoking phenotype. Smoking phenotype classification (Quitters, Reducers, Failures) had no significant effect on spirometric indices (FEV1, FVC and FEV1/FVC) with the exception of FEF25-75%, which significantly (P  =0.034) increased over the time among Quitters; their FEF25-75% (% predicted) improving from (means±S.D.) 85.7±15.6% at baseline (BL) to 100.8±14.6%. High prevalence of cough/phlegm (43.1%) and shortness of breath (SoB; 34.8%) was reported at BL with substantial reduction in their frequency at subsequent follow-up visits. These symptoms virtually disappeared very quickly in both quitters and reducers. Smokers invited to switch to ECs who completely abstained from smoking showed steady progressive improvements in their FEF25-75% Normalization of peripheral airways function was associated with improvement in respiratory symptoms, adding to the notion that abstaining from smoking can reverse tobacco harm in the lung.

  7. Effect of exposures to ambient ozone on ventilatory lung function in children

    SciTech Connect

    Higgins, I.T.; D'Arcy, J.B.; Gibbons, D.I.; Avol, E.L.; Gross, K.B. )

    1990-05-01

    This study was undertaken to determine if the ventilatory capacity of children is affected by hourly concentrations of ozone inhaled during their daily activity. Over a 3-wk period children who were attending a summer camp in the San Bernardino mountains of California performed spirometry up to three times per day during their stay at the camp. Ozone, oxides of nitrogen, sulfur dioxide, temperature, and relative humidity were measured continuously. Daily average measurements of total suspended particulate and the PM10 particulate fraction were also made. Hourly ozone concentrations at the time of testing varied between 20 and 245 ppb. Regressions of each individual's FEV1 and FVC supported the view that high ozone levels reduced these lung function parameters. The average regression coefficient for FEV1 on ozone was -0.39 ml/ppb (SEM = 0.12) and for FVC -0.44 ml/ppb (SEM = 0.15), both of which were significantly different from zero. Statistical allowance for temperature and humidity increased the magnitude of these slopes. Nitrogen dioxide never exceeded 40 ppb during the time of testing and averaged 13 ppb. Sulfur dioxide's highest measurement was 8 ppb and often was at the limit of detection. Neither NO2 nor SO2 was considered in the statistical modeling. Data were divided based on whether each subject had been exposed to levels of ozone in excess of the National Ambient Air Quality Standard (NAAQS) during the several hours previous to being tested. Exposures exceeding the NAAQS indicated a significant negative relationship between ozone and FEV1, FVC, and PEFR. Data for nonexceedance periods did not indicate this negative relationship for any of the three lung function parameters, but it could not be determined if this was due to an absence of an ozone effect or to a combination of the increased variability and decreased size of this data subset.

  8. Maternal 25-hydroxyvitamin D and its association with childhood atopic outcomes and lung function

    PubMed Central

    Wills, A K; Shaheen, S O; Granell, R; Henderson, A J; Fraser, W D; Lawlor, D A

    2013-01-01

    Background It has been suggested that maternal vitamin D status in pregnancy influences the risk of asthma and atopy in the offspring. The epidemiological evidence to support these claims is conflicting and may reflect chance findings and differences in how vitamin D was assessed. Objective To examine the association between blood total maternal 25-hydroxy vitamin D (25(OH)D) concentrations in pregnancy and offspring asthma, atopy and lung function in the largest birth cohort study to date. Methods Participants were largely of white European origin and resident in the South West of England. We examined the associations of maternal 25(OH)D concentrations in pregnancy with the following outcomes in the offspring: wheeze, asthma, atopy, eczema, hayfever, at mean age 7.5 years (n = 3652–4696 depending on outcome), IgE at 7 years (n = 2915) and lung function and bronchial responsiveness at mean age 8.7 years (n = 3728–3784). Results Sixty-eight per cent of mothers had sufficient (> 50 nmol/L) concentrations of 25(OH)D, 27% were insufficient (27.5–49.99 nmol/L) and 5% were deficient (< 27.5 nmol/L). There was no evidence to suggest that maternal 25(OH)D concentration in pregnancy was associated with any respiratory or atopic outcome in the offspring. These findings remained after adjustment for season of measurement and for potential confounders. There was also no evidence that these relationships followed a non-linear form and no evidence that either deficient or high concentrations of maternal 25(OH)D were associated with atopic or respiratory outcomes. Conclusions We found no evidence that maternal blood 25(OH)D concentration in pregnancy is associated with childhood atopic or respiratory outcomes. PMID:24074336

  9. Decrements in lung function related to arsenic in drinking water in West Bengal, India.

    PubMed

    von Ehrenstein, Ondine S; Mazumder, D N Guha; Yuan, Yan; Samanta, Sambit; Balmes, John; Sil, Arabinda; Ghosh, Nilima; Hira-Smith, Meera; Haque, Reina; Purushothamam, Radhika; Lahiri, Sarbari; Das, Subhankar; Smith, Allan H

    2005-09-15

    During 1998-2000, the authors investigated relations between lung function, respiratory symptoms, and arsenic in drinking water among 287 study participants, including 132 with arsenic-caused skin lesions, in West Bengal, India. The source population involved 7,683 participants who had been surveyed for arsenic-related skin lesions in 1995-1996. Respiratory symptoms were increased among men with arsenic-caused skin lesions (versus those without lesions), particularly "shortness of breath at night" (odds ratio (OR) = 2.8, 95% confidence interval (CI): 1.1, 7.6) and "morning cough" (OR = 2.8, 95% CI: 1.2, 6.6) in smokers and "shortness of breath ever" (OR = 3.8, 95% CI: 0.7, 20.6) in nonsmokers. Among men with skin lesions, the average adjusted forced expiratory volume in 1 second (FEV1) was reduced by 256.2 ml (95% CI: 113.9, 398.4; p < 0.001) and the average adjusted forced vital capacity (FVC) was reduced by 287.8 ml (95% CI: 134.9, 440.8; p < 0.001). In men, a 100-microg/liter increase in arsenic level was associated with a 45.0-ml decrease (95% CI: 6.2, 83.9) in FEV1 (p = 0.02) and a 41.4-ml decrease (95% CI: -0.7, 83.5) in FVC (p = 0.054). Women had lower risks than men of developing skin lesions and showed little evidence of respiratory effects. In this study, consumption of arsenic-contaminated water was associated with respiratory symptoms and reduced lung function in men, especially among those with arsenic-related skin lesions.

  10. Air Pollution, Airway Inflammation, and Lung Function in a Cohort Study of Mexico City Schoolchildren

    PubMed Central

    Barraza-Villarreal, Albino; Sunyer, Jordi; Hernandez-Cadena, Leticia; Escamilla-Nuñez, Maria Consuelo; Sienra-Monge, Juan Jose; Ramírez-Aguilar, Matiana; Cortez-Lugo, Marlene; Holguin, Fernando; Diaz-Sánchez, David; Olin, Anna Carin; Romieu, Isabelle

    2008-01-01

    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 of 158 asthmatic and 50 nonasthmatic school-age children, followed an average of 22 weeks. We conducted spirometric tests, measurements of fractional exhaled nitric oxide (FeNO), interleukin-8 (IL-8) in nasal lavage, and pH of exhaled breath condensate every 15 days during follow-up. Data were analyzed using linear mixed-effects models. Results An increase of 17.5 μg/m3 in the 8-hr moving average of PM2.5 levels (interquartile range) was associated with a 1.08-ppb increase in FeNO [95% confidence interval (CI), 1.01–1.16] and a 1.07-pg/mL increase in IL-8 (95% CI 0.98–1.19) in asthmatic children and a 1.16 pg/ml increase in IL-8 (95% CI, 1.00–1.36) in nonasthmatic children. The 5-day accumulated average of exposure to particulate matter < 2.5 μm in aerodynamic diamter (PM2.5) was significantly inversely associated with forced expiratory volume in 1 sec (FEV1) (p = 0.048) and forced vital capacity (FVC) (p = 0.012) in asthmatic children and with FVC (p = 0.021) in nonasthmatic children. FeNO and FEV1 were inversely associated (p = 0.005) in asthmatic children. Conclusions Exposure to PM2.5 resulted in acute airway inflammation and decrease in lung function in both asthmatic and nonasthmatic children. PMID:18560490

  11. Developmental regulation of DUOX1 expression and function in human fetal lung epithelial cells.

    PubMed

    Fischer, Horst; Gonzales, Linda K; Kolla, Venkatadri; Schwarzer, Christian; Miot, Françoise; Illek, Beate; Ballard, Philip L

    2007-06-01

    The purpose of this study was to determine the expression and cellular functions of the epithelial NADPH oxidase DUOX1 during alveolar type II cell development. When human fetal lung cells (gestational age 11-22 wk) were cultured to confluency on permeable filters, exposure of cells to a hormone mixture (dexamethasone, 8-Br-cAMP, and IBMX, together referred to as DCI) resulted in differentiation of cells into a mature type II phenotype as assessed by expression of lamellar bodies, surfactant proteins, and transepithelial electrical parameters. After 6 days in culture in presence of DCI, transepithelial resistance (2,616 +/- 529 Omega.cm(2)) and potential (-8.5 +/- 0.6 mV) indicated epithelial polarization. At the same time, treatment with DCI significantly increased the mRNA expression of DUOX1 ( approximately 21-fold), its maturation factor DUOXA1 ( approximately 12-fold), as well as DUOX protein ( approximately 12-fold), which was localized near the apical cell pole in confluent cultures. For comparison, in fetal lung specimens, DUOX protein was not detectable at up to 27 wk of gestational age but was strongly upregulated after 32 wk. Function of DUOX1 was assessed by measuring H(2)O(2) and acid production. Rates of H(2)O(2) production were increased by DCI treatment and blocked by small interfering RNA directed against DUOX1 or by diphenylene iodonium. DCI-treated cultures also showed increased intracellular acid production and acid release into the mucosal medium, and acid production was largely blocked by knockdown of DUOX1 mRNA. These data establish the regulated expression of DUOX1 during alveolar maturation, and indicate DUOX1 in alveolar H(2)O(2) and acid secretion by differentiated type II cells.

  12. 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.

  13. Roles of genotypes of beta2-adrenergic receptor in the relationship between eosinophil counts and lung function in Taiwanese adolescents.

    PubMed

    Lin, Ying-Chu; Lu, Cheng-Chan; Shen, Chen-Yang; Lei, Huan-Yao; Guo, Yueliang Leon; Su, Huey-Jen

    2003-05-01

    To examine the roles of genetic polymorphism of the beta2-adrenergic receptor (beta2AR) in the relationship between eosinophil (EOS) counts and eosinophil cationic protein (ECP) counts and lung function, we recruited a random sample from the 1996 nationwide survey of asthma prevalence in middle school children. A total of 149 subjects--42 asthmatic children, 38 asthmatics in remission (no reported attack for more than 12 months), and 69 nonasthmatics--completed a physical evaluation, pulmonary function test, and determination of EOS, ECP, and beta2AR genotypes at amino acids 16 and 27. Asthmatic children had higher EOS and ECP than did nonasthmatics. No association was found between asthma and beta2AR genotypes. Lung function was significantly and inversely correlated with EOS but not with ECP in asthmatic children. By genotype, an inverse correlation between lung function and EOS was found in asthmatic children with Arg16Arg or Gln27Glu. A nonsignificant but similar inverse correlation was found in asthmatic children with Arg16Gly or Gln27Gln. However, a nonsignificant but positive correlation was found in asthmatic children with Gly16Gly. In conclusion, we suggest that EOS is a better clinical indicator of airway inflammation than ECP when children are not having an asthma attack. The association between an increase of EOS and lower lung function can be differentiated by beta2AR genotypes at amino acid 16.

  14. 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

  15. COPD phenotypes on computed tomography and its correlation with selected lung function variables in severe patients

    PubMed Central

    da Silva, Silvia Maria Doria; Paschoal, Ilma Aparecida; De Capitani, Eduardo Mello; Moreira, Marcos Mello; Palhares, Luciana Campanatti; Pereira, Mônica Corso

    2016-01-01

    Background Computed tomography (CT) phenotypic characterization helps in understanding the clinical diversity of chronic obstructive pulmonary disease (COPD) patients, but its clinical relevance and its relationship with functional features are not clarified. Volumetric capnography (VC) uses the principle of gas washout and analyzes the pattern of CO2 elimination as a function of expired volume. The main variables analyzed were end-tidal concentration of carbon dioxide (ETCO2), Slope of phase 2 (Slp2), and Slope of phase 3 (Slp3) of capnogram, the curve which represents the total amount of CO2 eliminated by the lungs during each breath. Objective To investigate, in a group of patients with severe COPD, if the phenotypic analysis by CT could identify different subsets of patients, and if there was an association of CT findings and functional variables. Subjects and methods Sixty-five patients with COPD Gold III–IV were admitted for clinical evaluation, high-resolution CT, and functional evaluation (spirometry, 6-minute walk test [6MWT], and VC). The presence and profusion of tomography findings were evaluated, and later, the patients were identified as having emphysema (EMP) or airway disease (AWD) phenotype. EMP and AWD groups were compared; tomography findings scores were evaluated versus spirometric, 6MWT, and VC variables. Results Bronchiectasis was found in 33.8% and peribronchial thickening in 69.2% of the 65 patients. Structural findings of airways had no significant correlation with spirometric variables. Air trapping and EMP were strongly correlated with VC variables, but in opposite directions. There was some overlap between the EMP and AWD groups, but EMP patients had signicantly lower body mass index, worse obstruction, and shorter walked distance on 6MWT. Concerning VC, EMP patients had signicantly lower ETCO2, Slp2 and Slp3. Increases in Slp3 characterize heterogeneous involvement of the distal air spaces, as in AWD. Conclusion Visual assessment and

  16. Functional Genetic Polymorphisms in PP2A Subunit Genes Confer Increased Risks of Lung Cancer in Southern and Eastern Chinese

    PubMed Central

    Yang, Rongrong; Yang, Lei; Qiu, Fuman; Zhang, Lisha; Wang, Hui; Yang, Xiaorong; Deng, Jieqiong; Fang, Wenxiang; Zhou, Yifeng; Lu, Jiachun

    2013-01-01

    Protein phosphatase-2A (PP2A) is one of the major cellular serine-threonine phosphatases and functions as a tumor suppressor that negatively regulates the activity of some oncogenic kinases. Recent studies have reported that PP2A expression was suppressed during lung carcinogenesis, we there hypothesized that the single nucleotide polymorphisms (SNPs) in PP2A subunit genes may affect PP2A function and thus contribute to lung cancer susceptibility. In a two-stage case-control study with a total of 1559 lung cancer patients and 1679 controls, we genotyped eight putative functional SNPs and one identified functional SNP (i.e., rs11453459) in seven major PP2A subunits (i.e., PPP2R1A, PPP2R1B, PPP2CA, PPP2R2A, PPP2R2B, PPP2R5C, PPP2R5E) in southern and eastern Chinese. We found that rs11453459G (-G/GG) variant genotypes of PPP2R1A and the rs1255722AA variant genotype of PPP2R5E conferred increased risks of lung cancer (rs11453459, -G/GG vs. –: OR = 1.31, 95% CI = 1.13–1.51; rs1255722, AA vs. AG/GG: OR = 1.27, 95% CI = 1.07–1.51). After combined the two variants, the number of the adverse genotypes was positively associated with lung cancer risk in a dose-response manner (Ptrend  = 5.63×10−6). Further functional assay showed that lung cancer tissues carrying rs1255722AA variant genotype had a significantly lower mRNA level of PPP2R5E compared with tissues carrying GG/GA genotypes. However, such effect was not observed for the other SNPs and other combinations. Our findings suggested that the two functional variants in PPP2R1A and PPP2R5E and their combination are associated with lung cancer risk in Chinese, which may be valuable biomarkers to predict risk of lung cancer. PMID:24204789

  17. Impaired motor function in senescence-accelerated mouse prone 1 (SAMP1).

    PubMed

    Aoyama, Yo; Kim, Tae Yeon; Yoshimoto, Takuro; Niimi, Kimie; Takahashi, Eiki; Itakura, Chitoshi

    2013-06-17

    Senescence-accelerated mouse prone (SAMP) strains of mice show early onset of senescence, whereas senescence-accelerated mouse resistant (SAMR) strains are resistant to early senescence and serve as controls. Although SAMP6 and SAMP8 are established models of central nervous system alterations, it is unclear whether SAMP1/Sku (SAMP1) is characterized by brain alterations and dysfunction related to behavioral functioning. In the present study, behavioral tests (i.e., locomotor activity, Y-maze, rotating rod, hind-limb extension, and traction), histochemistry, and Western blot analyses were employed to study this mouse model using 2- and 4-month-old SAMP1 and age-matched control SAMR1. Although 2-month-old SAMP1 and SAMR1 showed similar activity, 4-month-old SAMP1 exhibited less activity than age-matched SAMR1 in locomotor activity and Y-maze tests. In rotating rod test, 2- and 4-month-old SAMP1 showed motor-coordination dysfunction. An abnormal extension reflex in the hind-limb test was observed in 2- and 4-month-old SAMP1. There were no significant differences between SAMP1 and SAMR1 with respect to grip strength in the traction test or alternation behavior in the Y-maze test. Histochemistry and Western blot analyses exhibited that cerebellar Purkinje cells in 4-month-old SAMP1 mice persistently expressed tyrosine hydroxylase. These results suggest that SAMP1 is a useful model for examining mechanisms underlying motor dysfunction. PMID:23583482

  18. Modification by antioxidant supplementation of changes in human lung function associated with air pollutant exposure: A systematic review

    PubMed Central

    2011-01-01

    Background Outdoor air pollution, given its demonstrated negative effects on the respiratory system, is a growing public health concern worldwide, particularly in urban cities. Human exposure to pollutants such as ozone, nitrogen oxides, combustion-related particulate matter and oxides of sulfur is responsible for significant cardiopulmonary morbidity and mortality in both adults and children. Several antioxidants have shown an ability to partially attenuate the negative physiological and functional impacts of air pollutants. This study systematically presents current data on the potential benefits of antioxidant supplementation on lung function outcomes associated with air pollutant exposures in intact humans. Methods Electronic databases (MEDLINE, EMBASE, BIOSIS Previews, Web of Sciences, Environmental Sciences & Pollution Management and TOXNET) were systematically searched for all studies published up to April 2009. Search terms relating to the concepts of respiratory tract diseases, respiratory function tests, air pollution, and antioxidants were used. Data was systematically abstracted from original articles that satisfied selection criteria for inclusion. For inclusion, the studies needed to have evaluated human subjects, given supplemental antioxidants, under conditions of known levels of air pollutants with measured lung function before and after antioxidant administration and/or air pollution exposure. Selected studies were summarized and conclusions presented. Results Eight studies investigated the role of antioxidant supplementation on measured lung function outcomes after subject exposure to air pollutants under controlled conditions; 5 of these studies concluded that pollutant-induced airway hyper-responsiveness and diminution in lung function measurements were attenuated by antioxidant supplementation. The remaining five studies took place under ambient (uncontrolled) exposures and unanimously concluded that antioxidant supplementations attenuate the

  19. [Combined pulmonary fibrosis and emphysema (CPFE)--limitation of usual lung function test and challenge at practice].

    PubMed

    Takai, Daiya

    2014-12-01

    Spirometry and the flow-volume curve test are commonly performed lung function tests. However, a unique clinical entity occasionally shows almost normal data in these tests, and is therefore missed on screening tests. The clinical entity of combined pulmonary emphysema and pulmdoary fibrosis was recognized and documented in the 90's in Japan, the USA, and Europe. Typical emphysema shows obstructive disorders, and pulmonary fibrosis shows restrictive disorders. Thus, the combination of both should lead to a combined disorder pattern in lung function tests, but this is not the case. In 2005, Cottin reported and redefined this combination of emphysema and fibrosis of the lung as "Combined Pulmonary Fibrosis and Emphysema" (CPFE). The patients are typically heavily smoking males who show an almost normal lung function. The upper lobe of these patients usually shows severe emphysema, which contributes to a static volume and a late phase in the forced volume test. On the other hand their lower lobe shows fibrotic change. The fibrotic portion contributes to early phase flow in the flow-volume curve. These mechanisms are a reason for the normal pattern appearance in lung function tests in CPFE patients. As a matter of course, these patients have damaged upper and lower lobes: their diffusing capacity of the lung shows a low performance, their saturation of blood hemoglobin decreases soon after light exercise, and their KL-6 (a blood marker of pulmonary fibrosis) usually shows a high value. They are considered a high risk group regarding complications of post-surgical treatment. Thus, when medical technologists identify suspicious cases, they should advise doctors to add diffusing capacity and KL-6 tests. (Review).

  20. The relative balance of GM-CSF and TGF-β1 regulates lung epithelial barrier function.

    PubMed

    Overgaard, Christian E; Schlingmann, Barbara; Dorsainvil White, StevenClaude; Ward, Christina; Fan, Xian; Swarnakar, Snehasikta; Brown, Lou Ann S; Guidot, David M; Koval, Michael

    2015-06-15

    Lung barrier dysfunction is a cardinal feature of the acute respiratory distress syndrome (ARDS). Alcohol abuse, which increases the risk of ARDS two- to fourfold, induces transforming growth factor (TGF)-β1, which increases epithelial permeability and impairs granulocyte/macrophage colony-stimulating factor (GM-CSF)-dependent barrier integrity in experimental models. We hypothesized that the relative balance of GM-CSF and TGF-β1 signaling regulates lung epithelial barrier function. GM-CSF and TGF-β1 were tested separately and simultaneously for their effects on lung epithelial cell barrier function in vitro. TGF-β1 alone caused an ∼ 25% decrease in transepithelial resistance (TER), increased paracellular flux, and was associated with projections perpendicular to tight junctions ("spikes") containing claudin-18 that colocalized with F-actin. In contrast, GM-CSF treatment induced an ∼ 20% increase in TER, decreased paracellular flux, and showed decreased colocalization of spike-associated claudin-18 with F-actin. When simultaneously administered to lung epithelial cells, GM-CSF antagonized the effects of TGF-β1 on epithelial barrier function in cultured cells. Given this, GM-CSF and TGF-β1 levels were measured in bronchoalveolar lavage (BAL) fluid from patients with ventilator-associated pneumonia and correlated with markers for pulmonary edema and patient outcome. In patient BAL fluid, protein markers of lung barrier dysfunction, serum α2-macroglobulin, and IgM levels were increased at lower ratios of GM-CSF/TGF-β1. Critically, patients who survived had significantly higher GM-CSF/TGF-β1 ratios than nonsurviving patients. This study provides experimental and clinical evidence that the relative balance between GM-CSF and TGF-β1 signaling is a key regulator of lung epithelial barrier function. The GM-CSF/TGF-β1 ratio in BAL fluid may provide a concentration-independent biomarker that can predict patient outcomes in ARDS.

  1. Structural-functional lung imaging using a combined CT-EIT and a Discrete Cosine Transformation reconstruction method

    NASA Astrophysics Data System (ADS)

    Schullcke, Benjamin; Gong, Bo; Krueger-Ziolek, Sabine; Soleimani, Manuchehr; Mueller-Lisse, Ullrich; Moeller, Knut

    2016-05-01

    Lung EIT is a functional imaging method that utilizes electrical currents to reconstruct images of conductivity changes inside the thorax. This technique is radiation free and applicable at the bedside, but lacks of spatial resolution compared to morphological imaging methods such as X-ray computed tomography (CT). In this article we describe an approach for EIT image reconstruction using morphologic information obtained from other structural imaging modalities. This leads to recon- structed images of lung ventilation that can easily be superimposed with structural CT or MRI images, which facilitates image interpretation. The approach is based on a Discrete Cosine Transformation (DCT) of an image of the considered transversal thorax slice. The use of DCT enables reduction of the dimensionality of the reconstruction and ensures that only conductivity changes of the lungs are reconstructed and displayed. The DCT based approach is well suited to fuse morphological image information with functional lung imaging at low computational costs. Results on simulated data indicate that this approach preserves the morphological structures of the lungs and avoids blurring of the solution. Images from patient measurements reveal the capabilities of the method and demonstrate benefits in possible applications.

  2. Structural-functional lung imaging using a combined CT-EIT and a Discrete Cosine Transformation reconstruction method

    PubMed Central

    Schullcke, Benjamin; Gong, Bo; Krueger-Ziolek, Sabine; Soleimani, Manuchehr; Mueller-Lisse, Ullrich; Moeller, Knut

    2016-01-01

    Lung EIT is a functional imaging method that utilizes electrical currents to reconstruct images of conductivity changes inside the thorax. This technique is radiation free and applicable at the bedside, but lacks of spatial resolution compared to morphological imaging methods such as X-ray computed tomography (CT). In this article we describe an approach for EIT image reconstruction using morphologic information obtained from other structural imaging modalities. This leads to recon- structed images of lung ventilation that can easily be superimposed with structural CT or MRI images, which facilitates image interpretation. The approach is based on a Discrete Cosine Transformation (DCT) of an image of the considered transversal thorax slice. The use of DCT enables reduction of the dimensionality of the reconstruction and ensures that only conductivity changes of the lungs are reconstructed and displayed. The DCT based approach is well suited to fuse morphological image information with functional lung imaging at low computational costs. Results on simulated data indicate that this approach preserves the morphological structures of the lungs and avoids blurring of the solution. Images from patient measurements reveal the capabilities of the method and demonstrate benefits in possible applications. PMID:27181695

  3. Estimation of ventilatory capacity in subjects with unacceptable lung function tests.

    PubMed

    Eisen, E A; Robins, J M

    1986-09-01

    Based on pulmonary function data collected annually for six years on 540 Vermont granite workers, FEV1 in survey 1 was estimated by extrapolating back from subsequent measurements. The extrapolation method was found to fit the observed data of subjects with reproducible initial values very well (R2 = 0.87). Extrapolated FEV1s for workers unable to perform an adequate pulmonary function test according to the standards of the American Thoracic Society were compared to extrapolated values in the rest of the cohort. After adjusting for confounding, subjects with test failure in survey 1 had a lower extrapolated FEV1 than the rest of the cohort (p = 0.07). The mean extrapolated FEV1 of the 71 workers with an initial test failure was only 95% of a predicted value derived from the group with reproducible data, and the per cent predicted decreased from 98% to 71% as the number of test failures in the follow-up surveys increased (p = 0.0004). The American Thoracic Society and the Epidemiology Standardization Project currently recommend that test failures be excluded from the analysis of epidemiological data. Our findings suggest that alternative strategies for handling non-reproducible lung function may need to be explored in order to avoid selection bias.

  4. Work capacity, thermal responses and lung function: united kingdom studies in the L.B.P.

    PubMed

    Weiner, J S

    1976-07-01

    Results of physiological studies from some ten U.K. Human Adaptability projects are presented. U.K. investigators made major contributions in developing and adapting techniques for the assussment under field conditions of work capacity, heat tolerance and respiratory function. The various ethnic studies of work capacity revealed the special role of body size and muscularity, as well as training, in determining the observed inter- and intra-population variance. The results on samples from U.K., New Guinea, the Caribbean, Israel, West and East Africa and the Ethiopian highlands gave no indication that genetic difference were significant in determining population differences. Differences in heat tolerance reflect in general the intensity of heat exposure, especially when combined with hard physical work. Indigenous peoples in Africa and New Guinea show some modification in sweating responses which do not appear to be genetically determined but are in some way, as yet not clearly established, attributable to long continued residence in tropical climates. In renal function of some seven ethnic groups were analysed in terms of lung volume bellows function, gas exchange and responses to excercise and carbon dioxide. The relative importance of genetic and non-genetic factors was examined. PMID:8802

  5. Effect of Wearing the Elevation Training Mask on Aerobic Capacity, Lung Function, and Hematological Variables.

    PubMed

    Porcari, John P; Probst, Lauren; Forrester, Karlei; Doberstein, Scott; Foster, Carl; Cress, Maria L; Schmidt, Katharina

    2016-06-01

    Altitude training and respiratory muscle training (RMT) have been reported to improve performance in elite and well-trained athletes. Several devices (altitude and RMT) have been developed to help athletes gain the competitive edge. The Elevation Training Mask 2.0 (ETM) purportedly simulates altitude training and has been suggested to increase aerobic capacity (VO2max), endurance performance, and lung function. Twenty-four moderately trained subjects completed 6 weeks of high-intensity cycle ergometer training. Subjects were randomized into a mask (n = 12) or control (n = 12) group. Pre and post-training tests included VO2max, pulmonary function, maximal inspiration pressure, hemoglobin and hematocrit. No significant differences were found in pulmonary function or hematological variables between or within groups. There was a significant improvement in VO2max and PPO in both the control (13.5% and 9.9%) and mask (16.5% and 13.6%) groups. There was no difference in the magnitude of improvement between groups. Only the mask group had significant improvements in ventilatory threshold (VT) (13.9%), power output (PO) at VT (19.3%), respiratory compensation threshold (RCT) (10.2%), and PO at RCT (16.4%) from pre to post-testing. The trends for improvements in VT and PO at VT between groups were similar to improvements in RCT and PO at RCT, but did not reach statistical significance (VT p = 0.06, PO at VT p = 0.170). Wearing the ETM while participating in a 6-week high-intensity cycle ergometer training program does not appear to act as a simulator of altitude, but more like a respiratory muscle training device. Wearing the ETM may improve specific markers of endurance performance beyond the improvements seen with interval training alone. Key pointsWearing the ETM during a 6-week high-intensity cycle ergometer training program may improve performance variables, such as VO2max, PPO, VT, PO at VT, RCT and PO at RCT.Wearing the ETM did not improve lung function, inspiratory

  6. Effect of Wearing the Elevation Training Mask on Aerobic Capacity, Lung Function, and Hematological Variables

    PubMed Central

    Porcari, John P.; Probst, Lauren; Forrester, Karlei; Doberstein, Scott; Foster, Carl; Cress, Maria L.; Schmidt, Katharina

    2016-01-01

    Altitude training and respiratory muscle training (RMT) have been reported to improve performance in elite and well-trained athletes. Several devices (altitude and RMT) have been developed to help athletes gain the competitive edge. The Elevation Training Mask 2.0 (ETM) purportedly simulates altitude training and has been suggested to increase aerobic capacity (VO2max), endurance performance, and lung function. Twenty-four moderately trained subjects completed 6 weeks of high-intensity cycle ergometer training. Subjects were randomized into a mask (n = 12) or control (n = 12) group. Pre and post-training tests included VO2max, pulmonary function, maximal inspiration pressure, hemoglobin and hematocrit. No significant differences were found in pulmonary function or hematological variables between or within groups. There was a significant improvement in VO2max and PPO in both the control (13.5% and 9.9%) and mask (16.5% and 13.6%) groups. There was no difference in the magnitude of improvement between groups. Only the mask group had significant improvements in ventilatory threshold (VT) (13.9%), power output (PO) at VT (19.3%), respiratory compensation threshold (RCT) (10.2%), and PO at RCT (16.4%) from pre to post-testing. The trends for improvements in VT and PO at VT between groups were similar to improvements in RCT and PO at RCT, but did not reach statistical significance (VT p = 0.06, PO at VT p = 0.170). Wearing the ETM while participating in a 6-week high-intensity cycle ergometer training program does not appear to act as a simulator of altitude, but more like a respiratory muscle training device. Wearing the ETM may improve specific markers of endurance performance beyond the improvements seen with interval training alone. Key points Wearing the ETM during a 6-week high-intensity cycle ergometer training program may improve performance variables, such as VO2max, PPO, VT, PO at VT, RCT and PO at RCT. Wearing the ETM did not improve lung function, inspiratory

  7. Effect of Wearing the Elevation Training Mask on Aerobic Capacity, Lung Function, and Hematological Variables.

    PubMed

    Porcari, John P; Probst, Lauren; Forrester, Karlei; Doberstein, Scott; Foster, Carl; Cress, Maria L; Schmidt, Katharina

    2016-06-01

    Altitude training and respiratory muscle training (RMT) have been reported to improve performance in elite and well-trained athletes. Several devices (altitude and RMT) have been developed to help athletes gain the competitive edge. The Elevation Training Mask 2.0 (ETM) purportedly simulates altitude training and has been suggested to increase aerobic capacity (VO2max), endurance performance, and lung function. Twenty-four moderately trained subjects completed 6 weeks of high-intensity cycle ergometer training. Subjects were randomized into a mask (n = 12) or control (n = 12) group. Pre and post-training tests included VO2max, pulmonary function, maximal inspiration pressure, hemoglobin and hematocrit. No significant differences were found in pulmonary function or hematological variables between or within groups. There was a significant improvement in VO2max and PPO in both the control (13.5% and 9.9%) and mask (16.5% and 13.6%) groups. There was no difference in the magnitude of improvement between groups. Only the mask group had significant improvements in ventilatory threshold (VT) (13.9%), power output (PO) at VT (19.3%), respiratory compensation threshold (RCT) (10.2%), and PO at RCT (16.4%) from pre to post-testing. The trends for improvements in VT and PO at VT between groups were similar to improvements in RCT and PO at RCT, but did not reach statistical significance (VT p = 0.06, PO at VT p = 0.170). Wearing the ETM while participating in a 6-week high-intensity cycle ergometer training program does not appear to act as a simulator of altitude, but more like a respiratory muscle training device. Wearing the ETM may improve specific markers of endurance performance beyond the improvements seen with interval training alone. Key pointsWearing the ETM during a 6-week high-intensity cycle ergometer training program may improve performance variables, such as VO2max, PPO, VT, PO at VT, RCT and PO at RCT.Wearing the ETM did not improve lung function, inspiratory

  8. IL-10 Gene Polymorphisms Are Associated with Post-Bronchiolitis Lung Function Abnormalities at Six Years of Age

    PubMed Central

    Lauhkonen, Eero; Koponen, Petri; Teräsjärvi, Johanna; Gröndahl-Yli-Hannuksela, Kirsi; Vuononvirta, Juho; Nuolivirta, Kirsi; Toikka, Jyri O.; Helminen, Merja; He, Qiushui; Korppi, Matti

    2015-01-01

    Aim Interleukin-10 (IL-10) has been associated with wheezing and asthma in children and the genetic variation of the IL-10 cytokine production may be linked to post-bronchiolitis lung function. We used impulse oscillometry (IOS) to evaluate the associations of IL10 polymorphisms with lung function at a median age of 6.3 years in children hospitalised for bronchiolitis before six months of age. Methods We performed baseline and post-exercise IOS on 103 former bronchiolitis patients. Data on single nucleotide polymorphisms (SNP) of IL10 rs1800896 (–1082G/A), rs1800871 (–819C/T), rs1800872 (–592C/A) were available for 99 children and of IL10 rs1800890 (–3575T/A) for 98 children. Results IL10 rs1800896, rs1800871 and rs1800872 combined genotype AA+CT+CA and carriage of haplotype ATA, respectively, were associated with higher resistance and lower reactance in baseline IOS in adjusted analyses. At IL10 rs1800890, the A/A-genotype and carriers of A-allele were associated with lower reactance in baseline IOS. There were no significant associations between the studied SNPs and airway hyper-reactivity to exercise. Conclusion Low-IL-10-producing polymorphisms in the IL-10 encoding gene were associated with obstructive lung function parameters, suggesting an important role for IL-10 in development of lung function deficit in early bronchiolitis patients. PMID:26473365

  9. Effects of coal combustion and gasification upon lung structure and function. Quarterly progress report, March 12, 1981

    SciTech Connect

    Not Available

    1981-01-01

    The overall objective of the proposed research is to correlate both structural and functional alterations in cells and tissues of the lung brought about by exposure to fluidized bed combustion and fixed bed gasification effluents and reagent grade oxides of metals known to be associated with coal combustion and gasification.

  10. CHANGES IN HEART RATE VARIABILITY AND LUNG FUNCTION OBSERVED IN NC PATROL TROOPERS EXPOSED TO PM AND AIR TOXICS

    EPA Science Inventory

    Changes in Heart Rate Variability and Lung Function in NC Patrol Troopers exposed to PM and Air Toxics

    Michael Riediker1, Wayne E Cascio1, Robert B Devlin2, Thomas Griggs1&4, Margaret Herbst1, Ronald W Williams3, Steve P McCorquodale4, Philip A Bromberg1
    1) University o...

  11. ACCOUNTING FOR THE ENDOGENEITY OF HEALTH AND ENVIRONMENTAL TOBACCO SMOKE EXPOSURE IN CHILDREN: AN APPLICATION TO CONTINUOUS LUNG FUNCTION

    EPA Science Inventory

    The goal of this study is to estimate an unbiased exposure effect of environmental tobacco smoke (ETS) exposure on children's continuous lung function. A majority of the evidence from health studies suggests that ETS exposure in early life contributes significantly to childhood ...

  12. The effect of gravitational acceleration on cardiac diastolic function: a biofluid mechanical perspective with initial results.

    PubMed

    Pantalos, George M; Bennett, Thomas E; Sharp, M Keith; Woodruff, Stewart J; O'Leary, Sean D; Gillars, Kevin J; Schurfranz, Thomas; Everett, Scott D; Lemon, Mark; Schwartz, John

    2005-08-01

    Echocardiographic measurements of astronaut cardiac function have documented an initial increase, followed by a progressive reduction in both left ventricular end-diastolic volume index and stroke volume with entry into microgravity (micro-G). The investigators hypothesize that the observed reduction in cardiac filling may, in part, be due to the absence of a gravitational acceleration dependent, intraventricular hydrostatic pressure difference in micro-G that exists in the ventricle in normal gravity (1-G) due to its size and anatomic orientation. This acceleration-dependent pressure difference, DeltaP(LV), between the base and the apex of the heart for the upright posture can be estimated to be 6660 dynes/cm(2) ( approximately 5 mm Hg) on Earth. DeltaP(LV) promotes cardiac diastolic filling on Earth, but is absent in micro-G. If the proposed hypothesis is correct, cardiac pumping performance would be diminished in micro-G. To test this hypothesis, ventricular function experiments were conducted in the 1-G environment using an artificial ventricle pumping on a mock circulation system with the longitudinal axis anatomically oriented for the upright posture at 45 degrees to the horizon. Additional measurements were made with the ventricle horizontally oriented to null DeltaP(LV)along the apex-base axis of the heart as would be the case for the supine posture, but resulting in a lesser hydrostatic pressure difference along the minor (anterior-posterior) axis. Comparative experiments were also conducted in the micro-G environment of orbital space flight on board the Space Shuttle. This paper reviews the use of an automated cardiovascular simulator flown on STS-85 and STS-95 as a Get Away Special payload to test this hypothesis. The simulator consisted of a pneumatically actuated, artificial ventricle connected to a closed-loop, fluid circuit with adjustable compliance and resistance elements to create physiologic pressure and flow conditions. Ventricular

  13. Effect of welding fume solubility on lung macrophage viability and function in vitro.

    PubMed

    Antonini, J M; Lawryk, N J; Murthy, G G; Brain, J D

    1999-11-26

    It was shown previously that fumes generated from stainless steel (SS) welding induced more pneumotoxicity and were cleared from the lungs at a slower rate than fumes collected from mild steel (MS) welding. These differences in response may be attributed to the metal composition of SS and MS welding fumes. In this study, fumes with vastly different metal profiles were collected during gas metal arc (GMA) or flux-covered manual metal arc (MMA) welding using two different consumable electrodes, SS or MS. The collected samples were suspended in saline, incubated for 24 h at 37 degrees C, and centrifuged. The supernatant (soluble components) and pellets (insoluble particulates) were separated, and their effects on lung macrophage viability and the release of reactive oxygen species (ROS) by macrophages were examined in vitro. The soluble MMA-SS sample was shown to be the most cytotoxic to macrophages and to have the greatest effect on their function as compared to the GMA-SS and GMA-MS fumes. Neither the soluble nor insoluble forms of the GMA-MS sample had any marked effect on macrophage viability. The flux-covered MMA-SS fume was found to be much more water soluble as compared to either the GMA-SS or the GMA-MS fumes. The soluble fraction of the MMA-SS samples was comprised almost entirely of Cr. The small fraction of the GMA-MS sample that was soluble contained Mn with little Fe, while a more complex mixture was observed in the soluble portion of the GMA-SS sample, which contained Mn, Ni, Fe, Cr, and Cu. Data show that differences in the solubility of welding fumes influence the viability and ROS production of macrophages. The presence of soluble metals, such as Fe, Cr, Ni, Cu, and Mn, and the complexes formed by these different metals are likely important in the pulmonary responses observed after welding fume exposure.

  14. Urinary Dialkyl Phosphate Concentrations and Lung Function Parameters in Adolescents and Adults: Results from the Canadian Health Measures Survey

    PubMed Central

    Ye, Ming; Beach, Jeremy; Martin, Jonathan W.; Senthilselvan, Ambikaipakan

    2015-01-01

    Background: Epidemiological studies have reported associations between lung function parameters and organophosphate (OP) pesticide exposures in agricultural oc