Long-term exposure to diesel engine exhaust induced lung function decline in a cross sectional study

PubMed Central

ZHANG, Li Ping; ZHANG, Xiao; DUAN, Hua Wei; MENG, Tao; NIU, Yong; HUANG, Chuan Feng; GAO, Wei Min; YU, Shan Fa; ZHENG, Yu Xin

2016-01-01

To clarify the effects of lung function following exposure to diesel engine exhaust (DEE), we recruited 137 diesel engine testing workers exposed to DEE and 127 non-DEE-exposed workers as study subjects. We performed lung function tests and measured cytokinesis-block micronucleus (CBMN) cytome index and levels of urinary polycyclic aromatic hydrocarbons (PAHs) metabolites. There was a significant decrease of forced expiratory volume in 1 second (FEV1), ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/ FVC), maximal mid expiratory flow curve (MMF), forced expiratory flow at 50% of FVC (FEF50%), and forced expiratory flow at 75% of FVC (FEF75%) in the DEE-exposed workers than non-DEE-exposed workers (all p<0.05). Among all study subjects, the decreases of FEF75% were associated with the increasing levels of PAHs metabolites (p<0.05), and there were negative correlations between FEV1, FEV1/FVC, MMF, FEF50%, and FEF75% with CBMN cytome index (all p<0.05). Our results show that long-term exposure to DEE can induce lung function decline which shows mainly obstructive changes and influence of small airways function. The decreased lung function is associated with internal dosage of DEE exposure, and accompany with the increasing CBMN cytome index. PMID:27334424

A neutrophil elastase inhibitor improves lung function during ex vivo lung perfusion.

PubMed

Harada, Masaaki; Oto, Takahiro; Otani, Shinji; Miyoshi, Kentaroh; Okada, Masanori; Iga, Norichika; Nishikawa, Hitoshi; Sugimoto, Seiichiro; Yamane, Masaomi; Miyoshi, Shinichiro

2015-12-01

Ex vivo lung perfusion (EVLP) has been used not only for graft evaluation but also for graft reconditioning prior to lung transplantation. Inflammatory cells such as neutrophils may cause additional graft injury during EVLP. Neutrophil elastase inhibitors protect lungs against neutrophil-induced lung injury, such as acute respiratory distress syndrome. This study aimed to investigate the effect of a neutrophil elastase inhibitor during EVLP. EVLP was performed for 4 h in bilateral pig lungs that had previously experienced warm ischemia for 2 h with or without a neutrophil elastase inhibitor (treated and control groups, respectively; n = 6). Following EVLP, the left lung was transplanted into a recipient pig, and this was followed by observation for 4 h. Pulmonary functions were observed both during EVLP and during the early post-transplant stage. During EVLP, decreases in neutrophil elastase levels (P < 0.001), the wet-dry weight ratio (P < 0.05), and pulmonary vascular resistance (P < 0.01) and increases in the PaO2/FiO2 ratio (P < 0.01) and pulmonary compliance (P < 0.05) were observed in the treated group. After transplantation, decreased pulmonary vascular resistance (P < 0.05) was observed in the treated group. A neutrophil elastase inhibitor attenuated the inflammatory response during EVLP and may decrease the incidence of lung reperfusion injury after transplantation.

Restoring Cystic Fibrosis Transmembrane Conductance Regulator Function Reduces Airway Bacteria and Inflammation in People with Cystic Fibrosis and Chronic Lung Infections.

PubMed

Hisert, Katherine B; Heltshe, Sonya L; Pope, Christopher; Jorth, Peter; Wu, Xia; Edwards, Rachael M; Radey, Matthew; Accurso, Frank J; Wolter, Daniel J; Cooke, Gordon; Adam, Ryan J; Carter, Suzanne; Grogan, Brenda; Launspach, Janice L; Donnelly, Seamas C; Gallagher, Charles G; Bruce, James E; Stoltz, David A; Welsh, Michael J; Hoffman, Lucas R; McKone, Edward F; Singh, Pradeep K

2017-06-15

Previous work indicates that ivacaftor improves cystic fibrosis transmembrane conductance regulator (CFTR) activity and lung function in people with cystic fibrosis and G551D-CFTR mutations but does not reduce density of bacteria or markers of inflammation in the airway. These findings raise the possibility that infection and inflammation may progress independently of CFTR activity once cystic fibrosis lung disease is established. To better understand the relationship between CFTR activity, airway microbiology and inflammation, and lung function in subjects with cystic fibrosis and chronic airway infections. We studied 12 subjects with G551D-CFTR mutations and chronic airway infections before and after ivacaftor. We measured lung function, sputum bacterial content, and inflammation, and obtained chest computed tomography scans. Ivacaftor produced rapid decreases in sputum Pseudomonas aeruginosa density that began within 48 hours and continued in the first year of treatment. However, no subject eradicated their infecting P. aeruginosa strain, and after the first year P. aeruginosa densities rebounded. Sputum total bacterial concentrations also decreased, but less than P. aeruginosa. Sputum inflammatory measures decreased significantly in the first week of treatment and continued to decline over 2 years. Computed tomography scans obtained before and 1 year after ivacaftor treatment revealed that ivacaftor decreased airway mucous plugging. Ivacaftor caused marked reductions in sputum P. aeruginosa density and airway inflammation and produced modest improvements in radiographic lung disease in subjects with G551D-CFTR mutations. However, P. aeruginosa airway infection persisted. Thus, measures that control infection may be required to realize the full benefits of CFTR-targeting treatments.

Stereotactic body radiotherapy for second primary lung cancer and intra-parenchymal lung metastasis in patients previously treated with surgery: evaluation of indications and predictors of decreased respiratory function.

PubMed

Ishihara, Takeaki; Yamada, Kazunari; Harada, Aya; Yukiue, Haruhiro; Tanahashi, Masayuki; Niwa, Hiroshi; Matsui, Takashi; Yokomura, Koshi; Ejima, Yasuo; Sasaki, Ryohei

2018-05-03

The adaptation criteria for administration of stereotactic body radiotherapy (SBRT) to patients with lung cancer who previously underwent surgery and subsequently developed a second primary lung cancer (SPLC) or intra-parenchymal lung metastasis (IPLM) are controversial, unlike the criteria for repeat surgery. We aimed to evaluate the feasibility of SBRT for these patients. Factors associated with decreased respiratory function were also evaluated. Sixty-nine patients with 89 lesions who underwent SBRT between 2008 and 2017 were analyzed. Of these, 29 were diagnosed with SPLC while the remaining 40 had IPLM. The distribution of histological types was as follows: squamous cell carcinoma (n = 13 lesions); adenocarcinoma (n = 25); non-small cell carcinoma (n = 1); unknown histological type (n = 49). The prescribed doses to the planning target volume (PTV) were 50 Gy in five fractions for 85 lesions and 60 Gy in 10 fractions for four lesions at PTV mean. Over a median follow-up period of 55 months, the 4-year overall survival and local control rates were 50.3% and 87.6%, respectively. Six patients experienced grade 2 radiation pneumonitis and one experienced grade 3. Two patients experienced grade 5 pulmonary fibrosis. Decreased respiratory function was observed in 10 patients (15.1%). On multivariate analysis, the presence of pulmonary disease before SBRT was the only statistically significant factor associated with decreased respiratory function. SBRT is safe and feasible in patients with SPLC or IPLM previously treated surgically. Pre-existing pulmonary disease was a predictive factor for decreased respiratory function.

Alveolar macrophages have a dual role in a rat model for trimellitic anhydride-induced occupational asthma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Valstar, Dingena L.; Schijf, Marcel A.; Nijkamp, Frans P.

2006-02-15

Occupational exposure to low molecular weight chemicals, like trimellitic anhydride (TMA), can result in occupational asthma. Alveolar macrophages (AMs) are among the first cells to encounter inhaled compounds. These cells can produce many different mediators that have a putative role in asthma. In this study, we examined the role of AMs in lung function and airway inflammation of rats exposed to TMA. Female Brown Norway rats were sensitized by dermal application of TMA or received vehicle alone on days 0 and 7. One day before challenge, rats received intratracheally either empty or clodronate-containing liposomes to deplete the lungs of AMs.more » On day 21, all rats were challenged by inhalation of TMA in air. Lung function parameters were measured before, during, within 1 h after, and 24 h after challenge. IgE levels and parameters of inflammation and tissue damage were assessed 24 h after challenge. Sensitization with TMA led to decreased lung function parameters during and within 1 h after challenge as compared to non-sensitized rats. AM depletion alleviated the TMA-induced drop in lung function parameters and induced a faster recovery compared to sham-depleted TMA-sensitized rats. It also decreased the levels of serum IgE 24 h after challenge, but did not affect the sensitization-dependent increase in lung lavage fluid IL-6 and tissue TNF-{alpha} levels. In contrast, AM depletion augmented the TMA-induced tissue damage and inflammation 24 h after challenge. AMs seem to have a dual role in this model for TMA-induced occupational asthma since they potentiate the immediate TMA-induced decrease in lung function but tended to dampen the TMA-induced inflammatory reaction 24 h later.« less

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

Fibroblast growth factor 10 haploinsufficiency causes chronic obstructive pulmonary disease.

PubMed

Klar, Joakim; Blomstrand, Peter; Brunmark, Charlott; Badhai, Jitendra; Håkansson, Hanna Falk; Brange, Charlotte Sollie; Bergendal, Birgitta; Dahl, Niklas

2011-10-01

Genetic factors influencing lung function may predispose to chronic obstructive pulmonary disease (COPD). The fibroblast growth factor 10 (FGF10) signalling pathway is critical for lung development and lung epithelial renewal. The hypothesis behind this study was that constitutive FGF10 insufficiency may lead to pulmonary disorder. Therefore investigation of the pulmonary functions of patients heterozygous for loss of function mutations in the FGF10 gene was performed. The spirometric measures of lung function from patients and non-carrier siblings were compared and both groups were related to matched reference data for normal human lung function. The patients show a significant decrease in lung function parameters when compared to control values. The average FEV1/IVC quota (FEV1%) for the patients is 0.65 (80% of predicted) and reversibility test using Terbutalin resulted in a 3.7% increase in FEV1. Patients with FGF10 haploinsufficiency have lung function parameters indicating COPD. A modest response to Terbutalin confirms an irreversible obstructive lung disease. These findings support the idea that genetic variants affecting the FGF10 signalling pathway are important determinants of lung function that may ultimately contribute to COPD. Specifically, the results show that FGF10 haploinsufficiency affects lung function measures providing a model for a dosage sensitive effect of FGF10 in the development of COPD.

Budesonide ameliorates lung function of the cigarette smoke-exposed rats through reducing matrix metalloproteinase-1 content

PubMed Central

Sun, Jiawei; Zhang, Ping; Zhang, Bin; Li, Kang; Li, Zhu; Li, Junhong; Zhang, Yongjian; Sun, Wuzhuang

2015-01-01

Objectives: This study was conducted to investigate an effect of inhaled budesonide on cigarette smoke-exposed lungs with a possible mechanism involved in the event. Methods: Rats were exposed to air (control) and cigarette smoke (smoking) in presence and absence of budesonide. Inflammatory cell count in bronchoalveolar lavage fluid (BALF), lung function testing, mean liner intercept (MLI) in lung tissue, mean alveolar number (MAN) and a ratio of bronchial wall thickness and external diameter (BWT/D) were determined in the grouped rats, respectively. Contents of matrix metalloproteinase (MMP)-1, MMP-2 and tissue inhibitor of metalloproteinase (TIMP)-2 productions in BALF were examined as well. Results: There were significant changes in the above assessments in the smoking rats as compared to those in the control rats (all P < 0.01 and 0.05). Budesonide inhalation significantly decreased the numbers of the BALF cells and partly reversed lung function decline in the challenged rats (P < 0.01 and 0.05). However, this corticosteroid did not influence pathological changes in fine structures of the tobacco smoke-exposed lungs. Treatment with budesonide resulted in an obvious decrease in the MMP-1 but not MMP-2 and TIMP-2 productions (P < 0.05). Conclusion: Inhaled budesonide mitigates the ongoing inflammatory process in the smoked lungs and ameliorates declining lung function through reducing MMP-1 content. PMID:26191209

Budesonide ameliorates lung function of the cigarette smoke-exposed rats through reducing matrix metalloproteinase-1 content.

PubMed

Sun, Jiawei; Zhang, Ping; Zhang, Bin; Li, Kang; Li, Zhu; Li, Junhong; Zhang, Yongjian; Sun, Wuzhuang

2015-01-01

This study was conducted to investigate an effect of inhaled budesonide on cigarette smoke-exposed lungs with a possible mechanism involved in the event. Rats were exposed to air (control) and cigarette smoke (smoking) in presence and absence of budesonide. Inflammatory cell count in bronchoalveolar lavage fluid (BALF), lung function testing, mean liner intercept (MLI) in lung tissue, mean alveolar number (MAN) and a ratio of bronchial wall thickness and external diameter (BWT/D) were determined in the grouped rats, respectively. Contents of matrix metalloproteinase (MMP)-1, MMP-2 and tissue inhibitor of metalloproteinase (TIMP)-2 productions in BALF were examined as well. There were significant changes in the above assessments in the smoking rats as compared to those in the control rats (all P<0.01 and 0.05). Budesonide inhalation significantly decreased the numbers of the BALF cells and partly reversed lung function decline in the challenged rats (P<0.01 and 0.05). However, this corticosteroid did not influence pathological changes in fine structures of the tobacco smoke-exposed lungs. Treatment with budesonide resulted in an obvious decrease in the MMP-1 but not MMP-2 and TIMP-2 productions (P<0.05). Inhaled budesonide mitigates the ongoing inflammatory process in the smoked lungs and ameliorates declining lung function through reducing MMP-1 content.

A Functional Role for KLF6-SV1 in Lung Adenocarcinoma Prognosis and Chemotherapy Response

PubMed Central

DiFeo, Analisa; Feld, Lauren; Rodriguez, Estefania; Wang, Christine; Beer, David G.; Martignetti, John A.; Narla, Goutham

2009-01-01

Kruppel-like factor 6 (KLF6) is a tumor suppressor gene that is functionally inactivated in human cancer by loss of heterozygosity, somatic mutation, decreased expression, and increased alternative splicing into an oncogenic splice variant, KLF6-SV1. Here we show that increased expression of KLF6-SV1 is associated with decreased survival in patients with lung adenocarcinoma. In addition, KLF6-SV1 is a novel antiapoptotic protein in lung cancer cell lines, and targeted reduction of KLF6-SV1 using siRNA induces apoptosis both alone and in combination with the chemotherapeutic drug cisplatin. Together, these findings highlight a critical role for KLF6-SV1 in lung cancer, and show a potential novel therapeutic strategy for the treatment of lung cancer. PMID:18250346

[Function in patients with chronic fibrocavernous tuberculosis].

PubMed

Nefedov, V B; Popova, L A; Shergina, E A

2008-01-01

Vital capacity (VC), forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), FEV1/VC%, PEF, MEF25, MEF50, MEF75, TLC, TGV, residual volume (RV), R(aw), R(in), R(ex), DLCO-SB, DLCO-SS, PaO2, and PaCO2 were determined in 62 patients with chronic fibrocavernous tuberculosis. Lung dysfunctions were detected in 96.8% of the patients. Changes in lung volumes and capacities were found in 90.3%, impaired bronchial patency was in 90.3%, and pulmonary gas exchange dysfunction was in 79.0%. The lung volume and capacity changes appeared as decreased VC and FVC, decreased and increased TLC, TGV, RV; impaired bronchial patency presented as decreased PEF, MEF25, MEF50, MEF75, and FEV1/VC%; and increased R(aw), R(in), R(ex); pulmonary gas exchange dysfunction manifested itself as reduced DLCO-SB, DLCO-SS, PaO2, and decreased and increased PaCO2. The magnitude of the observed functional changes ranges from slight to significant and drastic with a predominance of considerable and drastic changes in lung volumes and capacities and mild impairments of bronchial patency and pulmonary gas exchange function.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

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 regressionmore » 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.« less

Effects of Body Mass Index on Lung Function Index of Chinese Population

NASA Astrophysics Data System (ADS)

Guo, Qiao; Ye, Jun; Yang, Jian; Zhu, Changan; Sheng, Lei; Zhang, Yongliang

2018-01-01

To study the effect of body mass index (BMI) on lung function indexes in Chinese population. A cross-sectional study was performed on 10, 592 participants. The linear relationship between lung function and BMI was evaluated by multivariate linear regression analysis, and the correlation between BMI and lung function was assessed by Pearson correlation analysis. Correlation analysis showed that BMI was positively related with the decreasing of forced vital capacity (FVC), forced expiratory volume in one second (FEV1) and FEV1/FVC (P <0.05), the increasing of FVC% predicted value (FVC%pre) and FEV1% predicted value (FEV1%pre). These suggested that Chinese people can restrain the decline of lung function to prevent the occurrence and development of COPD by the control of BMI.

Violence exposure, a chronic psychosocial stressor, and childhood lung function

PubMed Central

Suglia, Shakira Franco; Ryan, Louise; Laden, Francine; Dockery, Douglas; Wright, Rosalind J

2011-01-01

Background Chronic psychosocial stressors, including violence, have been linked to neuropsychological and behavioral development in children as well as physiologic alterations that may lead to broader health effects. Methods We examined the relationship between violence and childhood lung function in a prospective birth cohort of 313 urban children 6 and 7 years of age. Mothers reported on their child’s lifetime exposure to community violence (ETV) and interparental conflict in the home [Conflict Tactics Scale (CTS)] within one year of the lung function assessment. Results In linear regression analyses, adjusting for maternal education, child’s age, race, birthweight, tobacco smoke exposure, and medical history, girls in the highest CTS verbal aggression tertile had a 5.5% (95% CI: −9.6, −1.5) decrease in percent predicted FEV1 and a 5.4% (95% CI: −9.7, −1.1) decrease in FVC compared to girls in the lowest tertile. The CTS verbal aggression subscale was associated with lung function among boys in the same direction, albeit this was not statistically significant. Boys in the highest ETV tertile had a 3.4% (95% CI: −8.0, 1.1) lower FEV1 and 5.3% lower (95% CI: −10.2, −0.4) FVC compared to boys in the lowest tertile. The ETV score was not a significant predictor of girl’s lung function. Conclusions Interparental conflict, specifically verbal aggression, and exposure to community violence were associated with decreased childhood lung function independent of socioeconomic status, tobacco smoke exposure, birthweight and respiratory illness history. Gender differences were noted based on the type of violence exposure which may warrant further exploration. PMID:18158365

Pulmonary functions in plastic factory workers: a preliminary study.

PubMed

Khaliq, Farah; Singh, Pawan; Chandra, Prakash; Gupta, Keshav; Vaney, Neelam

2011-01-01

Exposure to long term air pollution in the work environment may result in decreased lung functions and various other health problems. A significant occupational hazard to lung functions is experienced by plastic factory workers. The present study is planned to assess the pulmonary functions of workers in the plastic factory where recycling of pastic material was done. These workers were constantly exposed to fumes of various chemicals throughout the day. Thirty one workers of plastic factory were assessed for their pulmonary functions. Parameters were compared with 31 age and sex matched controls not exposed to the same environment. The pulmonary function tests were done using Sibelmed Datospir 120 B portable spirometer. A significant decrease in most of the flow rates (MEF 25%, MEF 50%, MEF 75% and FEF 25-75%) and most of the lung volumes and capacities (FVC, FEV1, VC, TV, ERV, MVV) were observed in the workers. Smoking and duration of exposure were not affecting the lung functions as the non smokers also showed a similar decrement in pulmonary functions. Similarly the workers working for less than 5 years also had decrement in pulmonary functions indicating that their lungs are being affected even if they have worked for one year. Exposure to the organic dust in the work environment should be controlled by adequate engineering measures, complemented by effective personal respiratory protection.

Lung function declines in patients with pulmonary sarcoidosis and increased respiratory epithelial permeability to sup 99m Tc-DTPA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chinet, T.; Dusser, D.; Labrune, S.

1990-02-01

Respiratory epithelial clearance of {sup 99m}Tc-DTPA (RC-Tc-DTPA) and pulmonary function tests (PFT) were determined at intervals of 6 or 12 months in 37 untreated, nonsmoking patients with sarcoidosis over a period of 6 to 36 months. PFT included the measurements of total lung capacity (TLC), vital capacity (VC), FEV1, and diffusing capacity for carbon monoxide. No difference was found between the respiratory clearance of {sup 113m}In-DTPA (2.25 +/- 1.00%/min) and RC-Tc-DTPA (2.29 +/- 1.11%/min) in eight patients with pulmonary sarcoidosis. Pulmonary function decreased 15% or more in at least 2 function tests during 11 follow-up periods, but it remained stablemore » during 47 follow-up periods. In patients whose lung function deteriorated, RC-Tc-DTPA increased to 3.51 +/- 1.55%/min; in contrast, in patients whose lung function remained stable, regardless of the initial values, RC-Tc-DTPA was normal (1.00 +/- 0.50%/min; p less than 0.001). In eight patients who were treated with corticosteroids, RC-Tc-DTPA decreased from 3.48 +/- 1.31%/min to 1.56 +/- 0.64%/min (p less than 0.001), and PFT improved. We conclude that in nonsmokers with pulmonary sarcoidosis, increased RC-Tc-DTPA is not related to dissociation of 99mTc from DTPA, RC-Tc-DTPA is increased when pulmonary function decreases, and, when increased, RC-Tc-DTPA decreases with corticosteroid therapy.« less

Lung volume quantified by MRI reflects extracellular-matrix deposition and altered pulmonary function in bleomycin models of fibrosis: effects of SOM230.

PubMed

Egger, Christine; Gérard, Christelle; Vidotto, Nella; Accart, Nathalie; Cannet, Catherine; Dunbar, Andrew; Tigani, Bruno; Piaia, Alessandro; Jarai, Gabor; Jarman, Elizabeth; Schmid, Herbert A; Beckmann, Nicolau

2014-06-15

Idiopathic pulmonary fibrosis is a progressive and lethal disease, characterized by loss of lung elasticity and alveolar surface area, secondary to alveolar epithelial cell injury, reactive inflammation, proliferation of fibroblasts, and deposition of extracellular matrix. The effects of oropharyngeal aspiration of bleomycin in Sprague-Dawley rats and C57BL/6 mice, as well as of intratracheal administration of ovalbumin to actively sensitized Brown Norway rats on total lung volume as assessed noninvasively by magnetic resonance imaging (MRI) were investigated here. Lung injury and volume were quantified by using nongated or respiratory-gated MRI acquisitions [ultrashort echo time (UTE) or gradient-echo techniques]. Lung function of bleomycin-challenged rats was examined additionally using a flexiVent system. Postmortem analyses included histology of collagen and hydroxyproline assays. Bleomycin induced an increase of MRI-assessed total lung volume, lung dry and wet weights, and hydroxyproline content as well as collagen amount. In bleomycin-treated rats, gated MRI showed an increased volume of the lung in the inspiratory and expiratory phases of the respiratory cycle and a temporary decrease of tidal volume. Decreased dynamic lung compliance was found in bleomycin-challenged rats. Bleomycin-induced increase of MRI-detected lung volume was consistent with tissue deposition during fibrotic processes resulting in decreased lung elasticity, whereas influences by edema or emphysema could be excluded. In ovalbumin-challenged rats, total lung volume quantified by MRI remained unchanged. The somatostatin analog, SOM230, was shown to have therapeutic effects on established bleomycin-induced fibrosis in rats. This work suggests MRI-detected total lung volume as readout for tissue-deposition in small rodent bleomycin models of pulmonary fibrosis. Copyright © 2014 the American Physiological Society.

Simvastatin mitigates functional and structural impairment of lung and right ventricle in a rat model of cigarette smoke-induced COPD.

PubMed

Wang, Yajie; Jiang, Xue; Zhang, Lihai; Wang, Lihong; Li, Zhu; Sun, Wuzhuang

2014-01-01

This study is conducted to investigate an effect of simvastatin on cigarette smoke-induced COPD. Rats were exposed to air (control) and cigarette smoke (smoking) in presence and absence of simvastatin. Heart and lung tissues were harvested for histopathologic and morphometric analysis. Body weight of rat, mean liner intercept (MLI), mean alveolar number (MAN), lung function test, mean pulmonary artery pressure (mPAP), right ventricular hypertrophy index (RVHI) and 5-HTT level in serum and BALF were examined in experimental rats, respectively. Application of simvastatin mitigated peribronchiolar inflammation and pulmonary bullae formed in the smoke-exposed lungs with weight gain as compared to the smoking rats (P < 0.05). Simvastatin-treated rats showed slight but significant decreases in MLI and MAN with a partial reversal of lung function decline (all P < 0.05). Treatment with simvastatin resulted in a significant decrease not only in mPAP and RVHI but also in a 5-HTT level in serum and BALF (P < 0.01 or 0.05) with a good correlation between the 5-HTT level and mPAP or RVHI (r = 0.693 and 0.479; 0.675 and 0.508). Simvastatin partly reverses lung function decline and attenuates structural impairments of lung and right ventricle possibly through reducing 5-HTT content in the model of COPD.

Simvastatin mitigates functional and structural impairment of lung and right ventricle in a rat model of cigarette smoke-induced COPD

PubMed Central

Wang, Yajie; Jiang, Xue; Zhang, Lihai; Wang, Lihong; Li, Zhu; Sun, Wuzhuang

2014-01-01

Objectives: This study is conducted to investigate an effect of simvastatin on cigarette smoke-induced COPD. Methods: Rats were exposed to air (control) and cigarette smoke (smoking) in presence and absence of simvastatin. Heart and lung tissues were harvested for histopathologic and morphometric analysis. Body weight of rat, mean liner intercept (MLI), mean alveolar number (MAN), lung function test, mean pulmonary artery pressure (mPAP), right ventricular hypertrophy index (RVHI) and 5-HTT level in serum and BALF were examined in experimental rats, respectively. Results: Application of simvastatin mitigated peribronchiolar inflammation and pulmonary bullae formed in the smoke-exposed lungs with weight gain as compared to the smoking rats (P < 0.05). Simvastatin-treated rats showed slight but significant decreases in MLI and MAN with a partial reversal of lung function decline (all P < 0.05). Treatment with simvastatin resulted in a significant decrease not only in mPAP and RVHI but also in a 5-HTT level in serum and BALF (P < 0.01 or 0.05) with a good correlation between the 5-HTT level and mPAP or RVHI (r = 0.693 and 0.479; 0.675 and 0.508). Conclusion: Simvastatin partly reverses lung function decline and attenuates structural impairments of lung and right ventricle possibly through reducing 5-HTT content in the model of COPD. PMID:25674219

Effects of budesonide on the lung functions, inflammation and apoptosis in a saline-lavage model of acute lung injury.

PubMed

Mokra, D; Kosutova, P; Balentova, S; Adamkov, M; Mikolka, P; Mokry, J; Antosova, M; Calkovska, A

2016-12-01

Diffuse alveolar injury, edema, and inflammation are fundamental signs of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Whereas the systemic administration of corticosteroids previously led to controversial results, this study evaluated if corticosteroids given intratracheally may improve lung functions and reduce edema formation, migration of cells into the lung and their activation in experimentally-induced ALI. In oxygen-ventilated rabbits, ALI was induced by repetitive saline lung lavage, until PaO2 decreased to < 26.7 kPa in FiO 2 1.0. Then, one group of animals was treated with corticosteroid budesonide (Pulmicort susp inh, AstraZeneca; 0.25 mg/kg) given intratracheally by means of inpulsion regime of high-frequency jet ventilation, while another group was non-treated, and both groups were oxygen-ventilated for following 5 hours. Another group of animals served as healthy controls. After sacrifice of animals, left lung was saline-lavaged and protein content was measured and cells in the lavage fluid were determined microscopically. Right lung tissue was used for estimation of edema formation (expressed as wet/dry weight ratio), for histomorphological investigation, immunohistochemical determination of apoptosis of lung cells, and for determination of markers of inflammation and lung injury (IL-1β, IL-6, IL-8, TNF-α, IFNγ, esRAGE, caspase-3) by ELISA methods. Levels of several cytokines were estimated also in plasma. Repetitive lung lavage worsened gas exchange, induced lung injury, inflammation and lung edema and increased apoptosis of lung epithelial cells. Budesonide reduced lung edema, cell infiltration into the lung and apoptosis of epithelial cells and decreased concentrations of proinflammatory markers in the lung and blood. These changes resulted in improved ventilation. Concluding, curative intratracheal treatment with budesonide alleviated lung injury, inflammation, apoptosis of lung epithelial cells and lung edema and improved lung functions in a lavage model of ALI. These findings suggest a potential of therapy with inhaled budesonide also for patients with ARDS.

Pleural plaques and their effect on lung function in Libby vermiculite miners.

PubMed

Clark, Kathleen A; Flynn, J Jay; Goodman, Julie E; Zu, Ke; Karmaus, Wilfried J J; Mohr, Lawrence C

2014-09-01

Multiple studies have investigated the relationship between asbestos-related pleural plaques (PPs) and lung function, with disparate and inconsistent results. Most use chest radiographs to identify PPs and simple spirometry to measure lung function. High-resolution CT (HRCT) scanning improves the accuracy of PP identification. Complete pulmonary function tests (PFTs), including spirometry, lung volumes, and diffusing capacity of the lung for carbon monoxide, provide a more definitive assessment of lung function. The goal of this study was to determine, using HRCT scanning and complete PFTs, the effect of PPs on lung function in Libby vermiculite miners. The results of HRCT scanning and complete PFTs performed between January 2000 and August 2012 were obtained from the medical records of 166 Libby vermiculite miners. Multivariate regression analyses with Tukey multivariate adjustment were used to assess statistical associations between the presence of PPs and lung function. Adjustments were made for age, BMI, smoking history, duration of employment, and years since last occupational asbestos exposure. Nearly 90% of miners (n = 149) had evidence of PPs on HRCT scan. No significant differences in spirometry results, lung volumes, or diffusing capacity of the lung for carbon monoxide were found between miners with PPs alone and miners with normal HRCT scans. Miners with both interstitial fibrosis and the presence of PPs had a significantly decreased total lung capacity in comparison with miners with normal HRCT scans (P = .02). Age, cumulative smoking history, and BMI were significant covariates that contributed to abnormal lung function. Asbestos-related PPs alone have no significant effect on lung function in Libby vermiculite miners.

Exponential analysis of the lung pressure-volume curve in patients with chronic pigeon-breeder's lung.

PubMed

Sansores, R; Perez-Padilla, R; Paré, P D; Selman, M

1992-05-01

Pigeon-breeder's lung (PBL) is extremely common in Mexico City and often progresses to irreversible pulmonary fibrosis. The exponential analysis of the lung pressure-volume (PV) curve (V = A - Be-kp) has been suggested as a method to separate the lung restriction caused by inflammation from that caused by pulmonary fibrosis; a significantly decreased value for the exponential constant, k, suggests a change in the mechanical properties of the functioning lung parenchyma, while a normal value accompanied by restriction suggests subtraction of lung units without a change in the mechanical properties of the functioning units. We measured lung volumes and static PV curves in 29 patients who had persistent lung restriction following a biopsy-proven diagnosis of PBL. Mean values in the 29 subjects were as follows: age, 43 +/- 13 years; TLC, 61 +/- 15 percent of predicted; VC, 46 +/- 19 percent of predicted; and k, 55 +/- 17 percent of predicted. Twenty-four of the 29 patients had values for k that were below the 95 percent confidence level, and five had "normal" values. There was no difference in TLC and VC (percent of predicted) between those with or without a decreased value for k. Four of five patients with a normal value for k improved subsequent to diagnosis, while only one of 21 patients with a decreased k improved. We conclude that increased lung elasticity manifested by a low value for k is common in patients with chronic PBL. These results support the observation of frequent irreversible lung fibrosis in these patients. Measurements of k could prove a good prognostic indicator at the time of initial diagnosis.

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...

[Oxidative stress, lung function and exposure to air pollutants in Mexican schoolchildren with and without asthma].

PubMed

Romero-Calderón, Ana Teresa; Moreno-Macías, Hortensia; Manrique-Moreno, Joel David Francisco; Riojas-Rodríguez, Horacio; Torres-Ramos, Yessica Dorín; Montoya-Estrada, Araceli; Hicks-Gómez, Juan José; Linares-Segovia, Benigno; Cárdenas, Beatriz; Bárcenas, Claudia; Barraza-Villarreal, Albino

2017-01-01

To assess the association between the air pollutants exposure on markers of oxidative stress and lung function in schoolchildren with and without asthma from Salamanca and Leon Guanajuato, Mexico. We realized determinations of oxidative stress biomarkers and lung function tests in 314 schoolchildren. Information of air pollutants (O3, SO2, CO, PM2.5 and PM10) were obtained from monitoring stations and multiple linear regression models were run to assess the association. An increase of 0.09 pmol in conjugated dienes was observed by exposure to PM10 lag 1 in asthmatics from Salamanca (p<0.05). The exposure to O3 during the same day increased the concentration of Lipohydroperoxides in 4.38 nmol in asthmatics of Salamanca, as well as in 2.31 nmol by exposure to PM10 lag 2 (p<0.05). The forced vital capacity decreased by 138 and 203 ml in children without asthma, respectively, due to exposure to carbon monoxide (p<0.05). Exposure to air pollutants increase oxidative stress and decreased lung function in schoolchildren, with and without asthma.

Lung function in North American Indian children: reference standards for spirometry, maximal expiratory flow volume curves, and peak expiratory flow.

PubMed

Wall, M A; Olson, D; Bonn, B A; Creelman, T; Buist, A S

1982-02-01

Reference standards of lung function was determined in 176 healthy North American Indian children (94 girls, 82 boys) 7 to 18 yr of age. Spirometry, maximal expiratory flow volume curves, and peak expiratory flow rate were measured using techniques and equipment recommended by the American Thoracic Society. Standing height was found to be an accurate predictor of lung function, and prediction equations for each lung function variable are presented using standing height as the independent variable. Lung volumes and expiratory flow rates in North American Indian children were similar to those previously reported for white and Mexican-American children but were greater than those in black children. In both boys and girls, lung function increased in a curvilinear fashion. Volume-adjusted maximal expiratory flow rates after expiring 50 or 75% of FVC tended to decrease in both sexes as age and height increased. Our maximal expiratory flow volume curve data suggest that as North American Indian children grow, lung volume increases at a slightly faster rate than airway size does.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sundar, Isaac K.; Hwang, Jae-Woong; Wu, Shaoping

Research highlights: {yields} Vitamin D deficiency is linked to accelerated decline in lung function. {yields} Levels of vitamin D receptor (VDR) are decreased in lungs of patients with COPD. {yields} VDR knock-out mouse showed increased lung inflammation and emphysema. {yields} This was associated with decline in lung function and increased MMPs. {yields} VDR knock-out mouse model is useful for studying the mechanisms of lung diseases. -- Abstract: Deficiency of vitamin D is associated with accelerated decline in lung function. Vitamin D is a ligand for nuclear hormone vitamin D receptor (VDR), and upon binding it modulates various cellular functions. Themore » level of VDR is reduced in lungs of patients with chronic obstructive pulmonary disease (COPD) which led us to hypothesize that deficiency of VDR leads to significant alterations in lung phenotype that are characteristics of COPD/emphysema associated with increased inflammatory response. We found that VDR knock-out (VDR{sup -/-}) mice had increased influx of inflammatory cells, phospho-acetylation of nuclear factor-kappaB (NF-{kappa}B) associated with increased proinflammatory mediators, and up-regulation of matrix metalloproteinases (MMPs) MMP-2, MMP-9, and MMP-12 in the lung. This was associated with emphysema and decline in lung function associated with lymphoid aggregates formation compared to WT mice. These findings suggest that deficiency of VDR in mouse lung can lead to an early onset of emphysema/COPD because of chronic inflammation, immune dysregulation, and lung destruction.« less

Spatiotemporal alterations in Sprouty-2 expression and tyrosine phosphorylation in nitrofen-induced pulmonary hypoplasia.

PubMed

Friedmacher, Florian; Gosemann, Jan-Hendrik; Fujiwara, Naho; Alvarez, Luis A J; Corcionivoschi, Nicolae; Puri, Prem

2013-11-01

Pulmonary hypoplasia (PH) is a life-threatening condition of newborns presenting with congenital diaphragmatic hernia (CDH). Sprouty-2 functions as a key regulator of fibroblast growth factor receptor (FGFR) signalling in developing foetal lungs. It has been reported that FGFR-mediated alveolarization is disrupted in nitrofen-induced PH. Sprouty-2 knockouts show severe defects in lung morphogenesis similar to nitrofen-induced PH. Upon FGFR stimulation, Sprouty-2 is tyrosine-phosphorylated, which is essential for its physiological function during foetal lung development. We hypothesized that Sprouty-2 expression and tyrosine phosphorylation are altered in nitrofen-induced PH. Time-pregnant rats received either nitrofen or vehicle on gestation day 9 (D9). Foetal lungs were dissected on D18 and D21. Pulmonary Sprouty-2 gene and protein expression levels were analyzed by qRT-PCR, Western blotting and immunohistochemical staining. Relative mRNA expression of Sprouty-2 was significantly decreased in hypoplastic lungs without CDH (0.1050±0.01 vs. 0.3125±0.01; P<.0001) and with CDH (0.1671±0.01 vs. 0.3125±0.01; P<.0001) compared to controls on D18. Protein levels of Sprouty-2 were markedly decreased in hypoplastic lungs on D18 with decreased tyrosine phosphorylation levels on D18 and D21 detected at the molecular weight of Sprouty-2 consistent with Sprouty-2 tyrosine phosphorylation. Sprouty-2 immunoreactivity was markedly decreased in hypoplastic lungs on D18 and D21. Spatiotemporal alterations in pulmonary Sprouty-2 expression and tyrosine phosphorylation during the late stages of foetal lung development may interfere with FGFR-mediated alveolarization in nitrofen-induced PH. © 2013.

The effect of CSF-1 administration on lung maturation in a mouse model of neonatal hyperoxia exposure.

PubMed

Jones, Christina V; Alikhan, Maliha A; O'Reilly, Megan; Sozo, Foula; Williams, Timothy M; Harding, Richard; Jenkin, Graham; Ricardo, Sharon D

2014-09-06

Lung immaturity due to preterm birth is a significant complication affecting neonatal health. Despite the detrimental effects of supplemental oxygen on alveolar formation, it remains an important treatment for infants with respiratory distress. Macrophages are traditionally associated with the propagation of inflammatory insults, however increased appreciation of their diversity has revealed essential functions in development and regeneration. Macrophage regulatory cytokine Colony-Stimulating Factor-1 (CSF-1) was investigated in a model of neonatal hyperoxia exposure, with the aim of promoting macrophages associated with alveologenesis to protect/rescue lung development and function. Neonatal mice were exposed to normoxia (21% oxygen) or hyperoxia (Hyp; 65% oxygen); and administered CSF-1 (0.5 μg/g, daily × 5) or vehicle (PBS) in two treatment regimes; 1) after hyperoxia from postnatal day (P)7-11, or 2) concurrently with five days of hyperoxia from P1-5. Lung structure, function and macrophages were assessed using alveolar morphometry, barometric whole-body plethysmography and flow cytometry. Seven days of hyperoxia resulted in an 18% decrease in body weight and perturbation of lung structure and function. In regime 1, growth restriction persisted in the Hyp + PBS and Hyp + CSF-1 groups, although perturbations in respiratory function were resolved by P35. CSF-1 increased CSF-1R+/F4/80+ macrophage number by 34% at P11 compared to Hyp + PBS, but was not associated with growth or lung structural rescue. In regime 2, five days of hyperoxia did not cause initial growth restriction in the Hyp + PBS and Hyp + CSF-1 groups, although body weight was decreased at P35 with CSF-1. CSF-1 was not associated with increased macrophages, or with functional perturbation in the adult. Overall, CSF-1 did not rescue the growth and lung defects associated with hyperoxia in this model; however, an increase in CSF-1R+ macrophages was not associated with an exacerbation of lung injury. The trophic functions of macrophages in lung development requires further elucidation in order to explore macrophage modulation as a strategy for promoting lung maturation.

[The dose response decrease of lung function associated with the urinary polycyclic aromatic hydrocarbons metabolites in coke oven workers].

PubMed

Hu, Die; Deng, Qi-fei; Huang, Su-li; He, Yun-feng; Guo, Huan; Wu, Tang-chun

2012-12-01

To analyze the relationship between metabolites of polycyclic aromatic hydrocarbons (PAHs) and lung function in coke oven workers, and to provide scientific basis for further exploring the potential mechanism and developing the preventing strategies of the workers' early lung damage. We measured carbon monoxide, sulfur dioxide, benzene soluble matter, particulate matters, and PAHs at different workplaces of a coke oven plant. Detailed information on demography and occupational health condition of 912 workers were collected. We divided these workers into control group and coke oven group according to their workplaces and the different concentrations of COEs in the environment. We detected 10 urinary PAH metabolites and lung function using gas chromatography-mass spectrometry and spirometric tests, respectively. FEV(1.0) (91.12 ± 13.31) and FEV(1.0)/FVC (108.61 ± 20.37) of the coke oven group is significantly lower than the control group (94.16 ± 15.57, 113.45 ± 19.70). In the coke oven group, the hydroxyphenanthrene and 1-hydroxypyrene are negatively correlated with FEV(1.0)/FVC (β = -0.136, β = -0.100), Ptrend < 0.05 for all. The dose response decrease of lung function is associated with the urinary PAH metabolites in coke oven workers. Indicated that the long exposure to PAHs may cause the early lung damage in coke oven workers, phenanthrene and pyrene may be the main factors.

The role of traffic noise on the association between air pollution and children's lung function.

PubMed

Franklin, Meredith; Fruin, Scott

2017-08-01

Although it has been shown that traffic-related air pollution adversely affects children's lung function, few studies have examined the influence of traffic noise on this association, despite both sharing a common source. Estimates of noise exposure (L dn, dB), and freeway and non-freeway emission concentrations of oxides of nitrogen (NO x , ppb) were spatially assigned to children in Southern California who were tested for forced vital capacity (FVC, n=1345), forced expiratory volume in 1s, (FEV 1, n=1332), and asthma. The associations between traffic-related NO x and these outcomes, with and without adjustment for noise, were examined using mixed effects models. Adjustment for noise strengthened the association between NO x and reduced lung function. A 14.5mL (95% CI -40.0, 11.0mL) decrease in FVC per interquartile range (13.6 ppb) in freeway NO x was strengthened to a 34.6mL decrease after including a non-linear function of noise (95% CI -66.3, -2.78mL). Similarly, a 6.54mL decrease in FEV 1 (95% CI -28.3, 15.3mL) was strengthened to a 21.1mL decrease (95% CI -47.6, 5.51) per interquartile range in freeway NO x . Our results indicate that where possible, noise should be included in epidemiological studies of the association between traffic-related air pollution on lung function. Without taking noise into account, the detrimental effects of traffic-related pollution may be underestimated. Copyright © 2017 Elsevier Inc. All rights reserved.

Adverse Respiratory Health and Hematological Alterations among Agricultural Workers Occupationally Exposed to Organophosphate Pesticides: A Cross-Sectional Study in North India

PubMed Central

Fareed, Mohd.; Pathak, Manoj Kumar; Bihari, Vipin; Kamal, Ritul; Srivastava, Anup Kumar; Kesavachandran, Chandrasekharan Nair

2013-01-01

Background Non-protective work practices followed by farm workers during spraying of pesticides lead to occupational exposure among them. Objective This study is designed to explore the respiratory health and hematological profile of agricultural workers occupationally exposed to OP pesticides. Materials and Methods A cross sectional study was undertaken among 166 pesticide sprayers working in mango orchards of Lucknow district in North India compared with 77 controls to assess the respiratory illness, lung functions, cholinesterase levels and hematological profile. A questionnaire based survey and clinical examination for respiratory health were conducted among study subjects. Lung function test was conducted among study subjects by using spirometer. Cholinesterase level as biomarker of OP pesticides and hematological profile of study subjects were investigated in the laboratory by following the standard protocols. Results Overall respiratory morbidity observed among exposed subjects was 36.75%. Symptoms for respiratory illness like dry cough, productive cough, wheezing, irritation of throat and blood stained sputum were found to be significantly more (p<0.05) among pesticide sprayers than controls. Lung function parameters viz. PEFR, FEV1, %PEFR predicted, %FEV1 predicted and FEV1/FVC were found to be significantly decreased (p<0.05) among pesticide sprayers as compared to controls. Exposure wise distribution of respiratory illness and lung functions among pesticide sprayers show that the exposure duration significantly elevates (p<0.05) the respiratory problems and significantly decreases (p<0.001) lung functions among pesticide sprayers. Activities of acetylcholinesterase and butyrylcholinesterase were found to be significantly depleted (p<0.001) among pesticide sprayers as compared to controls which show the exposure of OP pesticides among them. The hematological profile viz. RBC, WBC, monocytes, neutrophils, MCV, MCH, MCHC and platelet count were significantly altered (p<0.001) in pesticide sprayers than controls. Conclusion This study shows that the unsafe occupational exposure of OP pesticides causes respiratory illness, decreased lung functions and hematological alterations among pesticide sprayers. PMID:23936093

Adverse respiratory health and hematological alterations among agricultural workers occupationally exposed to organophosphate pesticides: a cross-sectional study in North India.

PubMed

Fareed, Mohd; Pathak, Manoj Kumar; Bihari, Vipin; Kamal, Ritul; Srivastava, Anup Kumar; Kesavachandran, Chandrasekharan Nair

2013-01-01

Non-protective work practices followed by farm workers during spraying of pesticides lead to occupational exposure among them. This study is designed to explore the respiratory health and hematological profile of agricultural workers occupationally exposed to OP pesticides. A cross sectional study was undertaken among 166 pesticide sprayers working in mango orchards of Lucknow district in North India compared with 77 controls to assess the respiratory illness, lung functions, cholinesterase levels and hematological profile. A questionnaire based survey and clinical examination for respiratory health were conducted among study subjects. Lung function test was conducted among study subjects by using spirometer. Cholinesterase level as biomarker of OP pesticides and hematological profile of study subjects were investigated in the laboratory by following the standard protocols. Overall respiratory morbidity observed among exposed subjects was 36.75%. Symptoms for respiratory illness like dry cough, productive cough, wheezing, irritation of throat and blood stained sputum were found to be significantly more (p<0.05) among pesticide sprayers than controls. Lung function parameters viz. PEFR, FEV1, %PEFR predicted, %FEV1 predicted and FEV1/FVC were found to be significantly decreased (p<0.05) among pesticide sprayers as compared to controls. Exposure wise distribution of respiratory illness and lung functions among pesticide sprayers show that the exposure duration significantly elevates (p<0.05) the respiratory problems and significantly decreases (p<0.001) lung functions among pesticide sprayers. Activities of acetylcholinesterase and butyrylcholinesterase were found to be significantly depleted (p<0.001) among pesticide sprayers as compared to controls which show the exposure of OP pesticides among them. The hematological profile viz. RBC, WBC, monocytes, neutrophils, MCV, MCH, MCHC and platelet count were significantly altered (p<0.001) in pesticide sprayers than controls. This study shows that the unsafe occupational exposure of OP pesticides causes respiratory illness, decreased lung functions and hematological alterations among pesticide sprayers.

Perivascular fluid cuffs decrease lung compliance by increasing tissue resistance.

PubMed

Lowe, Kevin; Alvarez, Diego F; King, Judy A; Stevens, Troy

2010-06-01

Lung inflammation causes perivascular fluid cuffs to form around extra-alveolar blood vessels; however, the physiologic consequences of such cuffs remain poorly understood. Herein, we tested the hypothesis that perivascular fluid cuffs, without concomitant alveolar edema, are sufficient to decrease lung compliance. Prospective, randomized, controlled study. Research laboratory. One hundred twenty male CD40 rats. To test this hypothesis, the plant alkaloid thapsigargin was used to activate store-operated calcium entry and increase cytosolic calcium in endothelium. Thapsigargin was infused into a central venous catheter of intact, sedated, and mechanically ventilated rats. Static and dynamic lung mechanics and hemodynamics were measured continuously. Thapsigargin produced perivascular fluid cuffs along extra-alveolar vessels but did not cause alveolar flooding or blood gas abnormalities. Lung compliance dose-dependently decreased after thapsigargin infusion, attributable to an increase in tissue resistance that was attributed to increased tissue damping and tissue elastance. Airway resistance was not changed. Neither central venous pressure nor left ventricular end diastolic pressure was altered by thapsigargin. Heart rate did not change, although thapsigargin decreased left ventricular systolic function sufficient to reduce cardiac output by 50%. Infusion of the type 4 phosphodiesterase inhibitor, rolipram, prevented thapsigargin from inducing perivascular cuffs and decreasing lung compliance. Rolipram also normalized pressure over time and corrected the deficit in cardiac output. Our findings resolve for the first time that perivascular cuff formation negatively impacts mechanical coupling between the bronchovascular bundle and the lung parenchyma, decreasing lung compliance without impacting central venous pressure.

77 FR 44198 - Approval and Promulgation of Implementation Plans; State of Florida: New Source Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-27

....e., lung disease, decreased lung function asthma attacks and certain cardiovascular issues... with heart and lung diseases. For more details regarding health effects and PM 2.5 see EPA's Web site...'' and ``minor source baseline date'' (including trigger dates) to establish the PM 2.5 NAAQS specific...

Optical properties of tissue, experimental results

NASA Astrophysics Data System (ADS)

Beek, Johan F.

1993-08-01

The effective attenuation coefficient of piglet lung was measured in vitro at 632.8 nm. Interstial fibres with isotropic tips were used to measure the fluence rate as a function of the distance from an isotropic light source. In vitro measurements at 632.8 nm on a lung that was insufflated with oxygen from 50 to 150 ml showed that the effective attenuation coefficient decreases as a function of the volume of air in the lung (at 50 ml /Jeff = 0.297 + 0.011 mnf1, at 100 ml lice 0.150 ± 0.007 mm-1, and at 150 ml /Jeff= 0.1136 + 0.015 mm-1). A single in vitro measurement at 790 nm at an insufflated lung volume of 100 ml gave a comparable result (ii ie = 0.175 + 0.004 mm-1). A ff decrease in effective attenuation coefficient with an ncrease in lung volume was explained by Mie-theory. The effective attenuation coefficient, calculated with 11, and g from Mie-theory, showed a deviation < 22% from the measured in vitro values.

The natural history of adult pulmonary Langerhans cell histiocytosis: a prospective multicentre study.

PubMed

Tazi, Abdellatif; de Margerie, Constance; Naccache, Jean Marc; Fry, Stéphanie; Dominique, Stéphane; Jouneau, Stéphane; Lorillon, Gwenaël; Bugnet, Emmanuelle; Chiron, Raphael; Wallaert, Benoit; Valeyre, Dominique; Chevret, Sylvie

2015-03-14

The natural history of pulmonary Langerhans cell histiocytosis (PLCH) has been unclear due to the absence of prospective studies. The rate of patients who experience an early progression of their disease is unknown. Additionally, conflicting effects of smoking cessation on the outcome of PLCH have been reported. In this prospective, multicentre study, 58 consecutive patients with newly diagnosed PLCH were comprehensively evaluated over a two-year period. Our objectives were to estimate the incidence of early progression of the disease and to evaluate the impact of smoking status on lung function outcomes. Lung function deterioration was defined as a decrease of at least 15% in FEV1 and/or FVC and/or DLCO, compared with baseline values. At each visit, smoking status was recorded based on the patients' self-reports and urinary cotinine measurements that were blinded for the patients. The cumulative incidence of lung function outcomes over time was estimated using the non-parametric Kaplan-Meier method. Multivariate Cox models with time-dependent covariates were used to calculate the hazards ratios of the lung function deterioration associated with smoking status with adjustment for potential confounders. The cumulative incidence of lung function deterioration at 24 months was 38% (22% for FEV1 and DLCO, and 9% for FVC). In the multivariate analysis, smoking status and PaO2 at inclusion were the only factors associated with the risk of lung function deterioration. The patients' smoking statuses markedly changed over time. Only 20% of the patients quit using tobacco for the entire study period. Nevertheless, being a non-smoker was associated with a decreased risk of subsequent lung function deterioration, even after adjustment for baseline predictive factors. By serial lung computed tomography, the extent of cystic lesions increased in only 11% of patients. Serial lung function evaluation on a three- to six-month basis is essential for the follow-up of patients with recently diagnosed PLCH to identify those who experience an early progression of their disease. These patients are highly addicted to tobacco, and robust efforts should be undertaken to include them in smoking cessation programs. ClinicalTrials.gov: No: NCT01225601 .

[Lung dysfunction in patients with severe chronic obstructive bronchitis].

PubMed

Nefedov, V B; Popova, L A; Shergina, E A

2005-01-01

VC, FVC, FEV1, FEV1/VC%, PEF, MEF25, MEF50, MEF75, TCL, TGV, RV, Raw, Rin, Rex, DLCO-SS, PaO2, and PaCO2 were determined in 36 patients with severe chronic obstructive lung disease (FEV1 < 50% of the normal value). All the patients were found to have impaired bronchial patency and changes in lung volumes and capacities; 83.3% of the patients had pulmonary gas exchange dysfunction. Impaired bronchial patency mainly appeared as decreased FEV1, FEV1/VC%, PEF, MEF25, MEF50, MEF75, Raw, Rin, Rex; altered lung volumes and capacities manifested by increased RV, TGV, and TLC, and by decreased VC and FVC; pulmonary gas exchange dysfunction showed up as lowered PaO2 and DLCO-SS, as decreased or increased PaCO2. The observed bronchial patency disorders varied from significant to severe; functional changes in lung volumes and capacities were mild to severe.

Paclitaxel-induced lung injury and its amelioration by parecoxib sodium.

PubMed

Liu, Wen-jie; Zhong, Zhong-jian; Cao, Long-hui; Li, Hui-ting; Zhang, Tian-hua; Lin, Wen-qian

2015-08-10

To investigate the mechanism of paclitaxel-induced lung injury and its amelioration by parecoxib sodium. In this study, rats were randomly divided into: the control group (Con); the paclitaxel chemotherapy group (Pac); the paclitaxel+ parecoxib sodium intervention group (Pac + Pare); and the parecoxib sodium group (Pare). We observed changes in alveolar ventilation function, alveolar-capillary membrane permeability, lung tissue pathology and measured the levels of inflammatory cytokines and cyclooxygenase-2 (Cox-2) in lung tissue, the expression of tight junction proteins (Zo-1 and Claudin-4). Compared with the Con group, the lung tissue of the Pac group showed significantly increased expression of Cox-2 protein (p < 0.01), significant lung tissue inflammatory changes, significantly increased expression of inflammatory cytokines, decreased expression of Zo-1 and Claudin-4 proteins (p < 0.01), increased alveolar-capillary membrane permeability (p < 0.01), and reduced ventilation function (p < 0.01). Notably, in Pac + Pare group, intraperitoneal injection of parecoxib sodium led to decreased Cox-2 and ICAM-1 levels and reduced inflammatory responses, the recovered expression of Zo-1 and Claudin-4, reduced level of indicators reflecting the high permeability state, and close-to-normal levels of ventilation function. Intervention by the Cox-2-specific inhibitor parecoxib sodium can block this damage.

Paclitaxel-induced lung injury and its amelioration by parecoxib sodium

PubMed Central

Liu, Wen-jie; Zhong, Zhong-jian; Cao, Long-hui; Li, Hui-ting; Zhang, Tian-hua; Lin, Wen-qian

2015-01-01

To investigate the mechanism of paclitaxel-induced lung injury and its amelioration by parecoxib sodium. In this study, rats were randomly divided into: the control group (Con); the paclitaxel chemotherapy group (Pac); the paclitaxel+ parecoxib sodium intervention group (Pac + Pare); and the parecoxib sodium group (Pare). We observed changes in alveolar ventilation function, alveolar-capillary membrane permeability, lung tissue pathology and measured the levels of inflammatory cytokines and cyclooxygenase-2 (Cox-2) in lung tissue, the expression of tight junction proteins (Zo-1 and Claudin-4). Compared with the Con group, the lung tissue of the Pac group showed significantly increased expression of Cox-2 protein (p < 0.01), significant lung tissue inflammatory changes, significantly increased expression of inflammatory cytokines, decreased expression of Zo-1 and Claudin-4 proteins (p < 0.01), increased alveolar-capillary membrane permeability (p < 0.01), and reduced ventilation function (p < 0.01). Notably, in Pac + Pare group, intraperitoneal injection of parecoxib sodium led to decreased Cox-2 and ICAM-1 levels and reduced inflammatory responses, the recovered expression of Zo-1 and Claudin-4, reduced level of indicators reflecting the high permeability state, and close-to-normal levels of ventilation function. Intervention by the Cox-2-specific inhibitor parecoxib sodium can block this damage. PMID:26256764

Genetic variant in the 3'-untranslated region of VEGFR1 gene influences chronic obstructive pulmonary disease and lung cancer development in Chinese population.

PubMed

Wang, Hui; Yang, Lei; Deng, Jieqiong; Wang, Bo; Yang, Xiaorong; Yang, Rongrong; Cheng, Mei; Fang, Wenxiang; Qiu, Fuman; Zhang, Xin; Ji, Weidong; Ran, Pixin; Zhou, Yifeng; Lu, Jiachun

2014-09-01

Lung inflammation and epithelial to mesenchymal transition (EMT) are two pathogenic features for the two contextual diseases: chronic obstructive pulmonary disease (COPD) and lung cancer. VEGFR1 (or FLT1) plays a certain role in promoting tumour growth, inflammation and EMT. To simultaneously test the association between the single nucleotide polymorphisms (SNPs) in VEGFR1 and risk of COPD and lung cancer would reveal genetic mechanisms shared by these two diseases and joint aetiology. We conducted a two-population hospital-based case-control study. Three potential functional SNPs (rs664393, rs7326277 and rs9554314) were genotyped in southern Chinese and validated in eastern Chinese to explore their associations with COPD risk in 1511 COPD patients and 1677 normal lung function controls, and with lung cancer risk in 1559 lung cancer cases and 1679 cancer-free controls. We also detected the function of the promising SNP. Individuals carrying the rs7326277C (CT+CC) variant genotypes of VEGFR1 had a significant decrease in risk of both COPD (OR = 0.78; 95% CI = 0.68-0.90) and lung cancer (OR = 0.79; 95% CI = 0.64-0.98), compared with those carrying the rs7326277TT genotype. Functional assays further showed that the rs7326277C genotypes had lower transcriptional activity and caused decreased VEGFR expression, compared with the rs7326277TT genotype. However, no significant association was observed for the other two SNPs (rs664393 and rs9554314) and either COPD or lung cancer risk. Our data suggested that the rs7326277C variant of VEGFR1 could reduce both COPD and lung cancer risk by lowering VEGFR1 mRNA expression; the SNP might be a common susceptible locus for both COPD and lung cancer. © The Author 2014. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Relaxation and Guided Imagery: A School-Based Intervention for Children with Asthma.

ERIC Educational Resources Information Center

Peck, Heather L.; Bray, Melissa A.; Kehle, Thomas J.

2003-01-01

This investigation analyzed the effect of relaxation and guided imagery on lung function and anxiety by employing a multiple baseline design across four middle school students with asthma. With the introduction of the intervention, it was found that lung function improved and anxiety decreased in all students. (Contains 63 references, 1 table, and…

Lung Function and Inflammatory responses in healthy young adults exposed to 0.06 ppm Ozone for 6.6 hours

EPA Science Inventory

Rationale: Exposure to ozone causes a decrease in spirometric lung function and an increase in airway inflammation in healthy young adults at concentrations as low as 0.08 ppm close to the the National Ambient Air Quality Standard for ground level ozone. Objectives: To test wheth...

Relationship between pulmonary function and indoor air pollution from coal combustion among adult residents in an inner-city area of southwest China

PubMed Central

Jie, Y.; Houjin, H.; Xun, M.; Kebin, L.; Xuesong, Y.; Jie, X.

2014-01-01

Few studies evaluate the amount of particulate matter less than 2.5 mm in diameter (PM2.5) in relation to a change in lung function among adults in a population. The aim of this study was to assess the association of coal as a domestic energy source to pulmonary function in an adult population in inner-city areas of Zunyi city in China where coal use is common. In a cross-sectional study of 104 households, pulmonary function measurements were assessed and compared in 110 coal users and 121 non-coal users (≥18 years old) who were all nonsmokers. Several sociodemographic factors were assessed by questionnaire, and ventilatory function measurements including forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), the FEV1/FVC ratio, and peak expiratory flow rate (PEFR) were compared between the 2 groups. The amount of PM2.5 was also measured in all residences. There was a significant increase in the relative concentration of PM2.5 in the indoor kitchens and living rooms of the coal-exposed group compared to the non-coal-exposed group. In multivariate analysis, current exposure to coal smoke was associated with a 31.7% decrease in FVC, a 42.0% decrease in FEV1, a 7.46% decrease in the FEV1/FVC ratio, and a 23.1% decrease in PEFR in adult residents. The slope of lung function decrease for Chinese adults is approximately a 2-L decrease in FVC, a 3-L decrease in FEV1, and an 8 L/s decrease in PEFR per count per minute of PM2.5 exposure. These results demonstrate the harmful effects of indoor air pollution from coal smoke on the lung function of adult residents and emphasize the need for public health efforts to decrease exposure to coal smoke. PMID:25296361

Partial liquid ventilation with perfluorocarbon improves gas exchange and decreases inflammatory response in oleic acid-induced lung injury in beagles.

PubMed

Suh, G Y; Chung, M P; Park, S J; Park, J W; Kim, H C; Kim, H; Han, J; Rhee, C H; Kwon, O J

1999-12-01

The aim of this study was to determine the effect of partial liquid ventilation (PLV) using a perfluorocarbon (PFC) on gas exchange and lung inflammatory response in a canine acute lung injury model. After inducing severe lung injury by oleic acid infusion, beagle dogs were randomized to receive either gas ventilation only (control group, n = 6) or PLV (PLV group, n = 7) by sequential instillation of 10 mL/kg of perfluorodecalin (PFC) at 30 min intervals till functional residual capacity was attained. Measurements were made every 30 min till 210 min. Then the lungs were removed and bronchoalveolar lavage (BAL) (35 mL/kg) was performed on the right lung and the left lung was submitted for histologic analysis. There was significant improvement in PaO2 and PaCO2 in the PLV group compared to the control group (p < 0.05) which was associated with a significant decrease in shunt (p < 0.05). There was no significant difference in parameters of lung mechanics and hemodynamics. There was a significant decrease in cell count and neutrophil percentage in BAL fluid and significantly less inflammation and exudate scores in histology in the PLV group (p < 0.05). We conclude that PLV with perfluorodecalin improves gas exchange and decreases inflammatory response in the acutely-injured lung.

Hemofiltration in ex vivo lung perfusion-a study in experimentally induced pulmonary edema.

PubMed

Nilsson, Tobias; Hansson, Christoffer; Wallinder, Andreas; Malm, Carl-Johan; Silverborn, Martin; Ricksten, Sven-Erik; Dellgren, Göran

2016-02-01

Ex vivo lung perfusion (EVLP) can potentially reduce pulmonary edema. In a pig model with induced pulmonary edema, we evaluated the effect of hemofiltration (HF) during EVLP on lung function, perfusate oncotic pressure, and lung weight. In anesthetized pigs (n = 14), pulmonary edema was induced by a balloon in the left atrium, combined with crystalloid infusion (20 mL/kg), for 2 hours. The lungs were harvested, stored cold for 2 hours, and randomized to EVLP, with or without a hemofilter (HF and noHF groups, respectively, n = 7 for each). EVLP was performed with cellular perfusate at a hematocrit of 10% to 15%. Oncotic pressure, lung performance, and weight were measured before and after 180 minutes of EVLP reconditioning with or without HF. After in vivo induction of edema, arterial oxygen tension (Pao2)/inspired oxygen fraction (Fio2), and compliance decreased by 63% and 16%, respectively. Pao2/Fio2 was considerably improved at first evaluation ex vivo in both groups. HF increased oncotic pressure by 43% and decreased lung weight by 15%. The effects were negligible in the noHF group. Compliance decreased in both groups during reconditioning, although less so in the HF group (P < .05). Pao2/Fio2, shunt fraction, and oxygen saturation remained unchanged in both groups. Pulmonary flow index decreased in both groups, and was partially reversed by nitroglycerin. Dorsal atelectatic consolidations were seen in both groups. In this lung-edema model, EVLP reconditioning with hyperoncotic solution did not affect the degree of lung edema. HF during EVLP increased perfusate oncotic pressure, decreased lung weight with beneficial effects on compliance, but did not improve lung oxygenation capacity. Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Lung function in type 2 diabetes: the Normative Aging Study.

PubMed

Litonjua, Augusto A; Lazarus, Ross; Sparrow, David; Demolles, Debbie; Weiss, Scott T

2005-12-01

Cross-sectional studies have noted that subjects with diabetes have lower lung function than non-diabetic subjects. We conducted this analysis to determine whether diabetic subjects have different rates of lung function change compared with non-diabetic subjects. We conducted a nested case-control analysis in 352 men who developed diabetes and 352 non-diabetic subjects in a longitudinal observational study of aging in men. We assessed lung function among cases and controls at three time points: Time0, prior to meeting the definition of diabetes; Time1, the point when the definition of diabetes was met; and Time2, the most recent follow-up exam. Cases had lower forced expiratory volume in 1s (FEV1) and forced vital capacity (FVC) at all time points, even with adjustment for age, height, weight, and smoking. In multiple linear regression models adjusting for relevant covariates, there were no differences in rates of FEV1 or FVC change over time between cases and controls. Men who are predisposed to develop diabetes have decreased lung function many years prior to the diagnosis, compared with men who do not develop diabetes. This decrement in lung function remains after the development of diabetes. We postulate that mechanisms involved in the insulin resistant state contribute to the diminished lung function observed in our subjects.

Decreased Lung Perfusion After Breast/Chest Wall Irradiation: Quantitative Results From a Prospective Clinical Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liss, Adam L., E-mail: adamliss68@gmail.com; Marsh, Robin B.; Kapadia, Nirav S.

Purpose: To quantify lung perfusion changes after breast/chest wall radiation therapy (RT) using pre- and post-RT single photon emission computed tomography/computed tomography (SPECT/CT) attenuation-corrected perfusion scans; and correlate decreased perfusion with adjuvant RT dose for breast cancer in a prospective clinical trial. Methods and Materials: As part of an institutional review board–approved trial studying the impact of RT technique on lung function in node-positive breast cancer, patients received breast/chest wall and regional nodal irradiation including superior internal mammary node RT to 50 to 52.2 Gy with a boost to the tumor bed/mastectomy scar. All patients underwent quantitative SPECT/CT lung perfusion scanningmore » before RT and 1 year after RT. The SPECT/CT scans were co-registered, and the ratio of decreased perfusion after RT relative to the pre-RT perfusion scan was calculated to allow for direct comparison of SPECT/CT perfusion changes with delivered RT dose. The average ratio of decreased perfusion was calculated in 10-Gy dose increments from 0 to 60 Gy. Results: Fifty patients had complete lung SPECT/CT perfusion data available. No patient developed symptoms consistent with pulmonary toxicity. Nearly all patients demonstrated decreased perfusion in the left lung according to voxel-based analyses. The average ratio of lung perfusion deficits increased for each 10-Gy increment in radiation dose to the lung, with the largest changes in regions of lung that received 50 to 60 Gy (ratio 0.72 [95% confidence interval 0.64-0.79], P<.001) compared with the 0- to 10-Gy region. For each increase in 10 Gy to the left lung, the lung perfusion ratio decreased by 0.06 (P<.001). Conclusions: In the assessment of 50 patients with node-positive breast cancer treated with RT in a prospective clinical trial, decreased lung perfusion by SPECT/CT was demonstrated. Our study allowed for quantification of lung perfusion defects in a prospective cohort of breast cancer patients for whom attenuation-corrected SPECT/CT scans could be registered directly to RT treatment fields for precise dose estimates.« less

Receptor for advanced glycation endproducts (RAGE) maintains pulmonary structure and regulates the response to cigarette smoke.

PubMed

Wolf, Lisa; Herr, Christian; Niederstraßer, Julia; Beisswenger, Christoph; Bals, Robert

2017-01-01

The receptor for advanced glycation endproducts (RAGE) is highly expressed in the lung but its physiological functions in this organ is still not completely understood. To determine the contribution of RAGE to physiological functions of the lung, we analyzed pulmonary mechanics and structure of wildtype and RAGE deficient (RAGE-/-) mice. RAGE deficiency spontaneously resulted in a loss of lung structure shown by an increased mean chord length, increased respiratory system compliance, decreased respiratory system elastance and increased concentrations of serum protein albumin in bronchoalveolar lavage fluids. Pulmonary expression of RAGE was mainly localized on alveolar epithelial cells and alveolar macrophages. Primary murine alveolar epithelial cells isolated from RAGE-/- mice revealed an altered differentiation and defective barrier formation under in vitro conditions. Stimulation of interferone-y (IFNy)-activated alveolar macrophages deficient for RAGE with Toll-like receptor (TLR) ligands resulted in significantly decreased release of proinflammatory cytokines and chemokines. Exposure to chronic cigarette smoke did not affect emphysema-like changes in lung parenchyma in RAGE-/- mice. Acute cigarette smoke exposure revealed a modified inflammatory response in RAGE-/- mice that was characterized by an influx of macrophages and a decreased keratinocyte-derived chemokine (KC) release. Our data suggest that RAGE regulates the differentiation of alveolar epithelial cells and impacts on the development and maintenance of pulmonary structure. In cigarette smoke-induced lung pathology, RAGE mediates inflammation that contributes to lung damage.

“Pulmonary Effects of Maternal Smoking on the Fetus and Child: Effects on Lung Development, Respiratory Morbidities, and Life Long Lung Health”

PubMed Central

McEvoy, Cindy T.; Spindel, Eliot R.

2016-01-01

Summary Maternal smoking during pregnancy is the largest preventable cause of abnormal in-utero lung development. Despite well known risks, rates of smoking during pregnancy have only slightly decreased over the last ten years, with rates varying from 5-40% worldwide resulting in tens of millions of fetal exposures. Despite multiple approaches to smoking cessation about 50% of smokers will continue to smoke during pregnancy. Maternal genotype plays an important role in the likelihood of continued smoking during pregnancy and the degree to which maternal smoking will affect the fetus. The primary effects of maternal smoking on offspring lung function and health are decreases in forced expiratory flows, decreased passive respiratory compliance, increased hospitalization for respiratory infections, and an increased prevalence of childhood wheeze and asthma. Nicotine appears to be the responsible component of tobacco smoke that affects lung development, and some of the effects of maternal smoking on lung development can be prevented by supplemental vitamin C. Because nicotine is the key agent for affecting lung development, e-cigarette usage during pregnancy is likely to be as dangerous to fetal lung development as is maternal smoking. PMID:27639458

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

The Influence of Type 1 Diabetes Mellitus on Pulmonary Function and Exercise Capacity - Results from the Study of Health in Pomerania (SHIP).

PubMed

Stubbe, Beate; Schipf, Sabine; Schäper, Christoph; Felix, Stephan B; Steveling, Antje; Nauck, Matthias; Völzke, Henry; Wallaschofski, Henri; Friedrich, Nele; Ewert, Ralf; Ittermann, Till; Gläser, Sven

2017-01-01

Background: Diabetes mellitus Type 1 (T1DM) is associated with metabolic and microvascular diseases as part of a multi-organ and multi-systemic disorder. The dense network of capillary vessels in the lungs may change during the course of the development of microangiopathy. The connective tissue as well as alveoli may be subjected to non-enzymatic glycosylation of proteins which may in turn affect pulmonary function. Previous studies investigating lung function in patients with type 1 diabetes have only been performed on small numbers of patients. Our study is based on population data of the Study of Health in Pomerania (SHIP). Objective: To investigate the influence of metabolic control on pulmonary system function and to establish a decreased pulmonary system function as a late complication of T1DM in a population based setting. Methods: The study is a case matched study with multiple controls based on participants with T1DM (SHIP-DM-1, n=73) and non-diabetics (SHIP-1, n=292) from the population based study of Pomerania. Data on lung function and exercise performance stratified by age, sex, body mass index and smoking habits in participants with T1DM and without diabetes were matched. Results: Participants with T1DM showed a significantly lower total lung capacity, residual volume and forced vital capacity. The transfer factor for carbon monoxide, the maximum power output and oxygen uptake during exercise were significantly decreased in comparison to the general population without diabetes. Conclusion: The pattern of abnormal pulmonary function as observed in the present study with a reduction in lung volume parameters and reduced oxygen uptake in participants with T1DM suggests a restrictive type of lung disease caused by an intrinsic lung tissue derangement as well as pulmonary microangiopathy. © Georg Thieme Verlag KG Stuttgart · New York.

Four SNPs and Systemic Level of FOXP3 in Smokers and Patients with Chronic Obstructive Pulmonary Disease.

PubMed

Chu, Shuyuan; Zhong, Xiaoning; Zhang, Jianquan; Lai, Xiaoying; Xie, Jiajun; Li, Yu

2016-12-01

Forkhead box P3 (FOXP3) is the essential transcription factor for the function of regulatory T-cell (Treg). However, the gene mutation of FOXP3 in patients with chronic obstructive pulmonary disease (COPD) at different stages has not been reported. We aim to investigate four single nucleotide polymorphisms (SNPs) and the mRNA expression of FOXP3 in smokers with normal lung function and smokers with COPD at different stages. FOXP3 mRNA expression and SNPs in FOXP3 were assessed in nonsmokers with normal lung function (N), smokers with normal lung function (S), smokers with COPD in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1 or 2 grade (COPD 1-2), and smokers with COPD in GOLD 3 or 4 grade (COPD 3-4). In peripheral blood sample, FOXP3 mRNA was assessed using real-time quantitative PCR and SNPs were analyzed by TaqMan PCR. FOXP3 mRNA level in peripheral blood sample was decreased when COPD was aggravated. The frequency of FOXP3 rs5902434 genotype del/del and allele del are lower in COPD 1-2 and COPD 3-4 than that in N or S. The rs5902434 genotype del/del and allele del were, respectively, associated with decreased risk of COPD and lung function decline. The rs5902434 genotypic distribution was correlated with FOXP3 mRNA level. In conclusion, both FOXP3 rs5902434 genotypes and alleles were differently distributed in COPD patients and smokers with normal lung function. The distribution of del/del genotype was associated with systemic expression of FOXP3 mRNA. More research is needed to explore the role of FOXP3 gene polymorphism in immunoinflammation of COPD.

Influence of Lung Function and Sleep-disordered Breathing on All-Cause Mortality. A Community-based Study.

PubMed

Putcha, Nirupama; Crainiceanu, Ciprian; Norato, Gina; Samet, Jonathan; Quan, Stuart F; Gottlieb, Daniel J; Redline, Susan; Punjabi, Naresh M

2016-10-15

Whether sleep-disordered breathing (SDB) severity and diminished lung function act synergistically to heighten the risk of adverse health outcomes remains a topic of significant debate. The current study sought to determine whether the association between lower lung function and mortality would be stronger in those with increasing severity of SDB in a community-based cohort of middle-aged and older adults. Full montage home sleep testing and spirometry data were analyzed on 6,173 participants of the Sleep Heart Health Study. Proportional hazards models were used to calculate risk for all-cause mortality, with FEV 1 and apnea-hypopnea index (AHI) as the primary exposure indicators along with several potential confounders. All-cause mortality rate was 26.9 per 1,000 person-years in those with SDB (AHI ≥5 events/h) and 18.2 per 1,000 person-years in those without (AHI <5 events/h). For every 200-ml decrease in FEV 1 , all-cause mortality increased by 11.0% in those without SDB (hazard ratio, 1.11; 95% confidence interval, 1.08-1.13). In contrast, for every 200-ml decrease in FEV 1 , all-cause mortality increased by only 6.0% in participants with SDB (hazard ratio, 1.06; 95% confidence interval, 1.04-1.09). Additionally, the incremental influence of lung function on all-cause mortality was less with increasing severity of SDB (P value for interaction between AHI and FEV 1 , 0.004). Lung function was associated with risk for all-cause mortality. The incremental contribution of lung function to mortality diminishes with increasing severity of SDB.

Influence of Lung Function and Sleep-disordered Breathing on All-Cause Mortality. A Community-based Study

PubMed Central

Putcha, Nirupama; Crainiceanu, Ciprian; Norato, Gina; Samet, Jonathan; Quan, Stuart F.; Gottlieb, Daniel J.; Redline, Susan

2016-01-01

Rationale: Whether sleep-disordered breathing (SDB) severity and diminished lung function act synergistically to heighten the risk of adverse health outcomes remains a topic of significant debate. Objectives: The current study sought to determine whether the association between lower lung function and mortality would be stronger in those with increasing severity of SDB in a community-based cohort of middle-aged and older adults. Methods: Full montage home sleep testing and spirometry data were analyzed on 6,173 participants of the Sleep Heart Health Study. Proportional hazards models were used to calculate risk for all-cause mortality, with FEV1 and apnea–hypopnea index (AHI) as the primary exposure indicators along with several potential confounders. Measurements and Main Results: All-cause mortality rate was 26.9 per 1,000 person-years in those with SDB (AHI ≥5 events/h) and 18.2 per 1,000 person-years in those without (AHI <5 events/h). For every 200-ml decrease in FEV1, all-cause mortality increased by 11.0% in those without SDB (hazard ratio, 1.11; 95% confidence interval, 1.08–1.13). In contrast, for every 200-ml decrease in FEV1, all-cause mortality increased by only 6.0% in participants with SDB (hazard ratio, 1.06; 95% confidence interval, 1.04–1.09). Additionally, the incremental influence of lung function on all-cause mortality was less with increasing severity of SDB (P value for interaction between AHI and FEV1, 0.004). Conclusions: Lung function was associated with risk for all-cause mortality. The incremental contribution of lung function to mortality diminishes with increasing severity of SDB. PMID:27105053

Tumor-propagating cells and Yap/Taz activity contribute to lung tumor progression and metastasis

PubMed Central

Lau, Allison N; Curtis, Stephen J; Fillmore, Christine M; Rowbotham, Samuel P; Mohseni, Morvarid; Wagner, Darcy E; Beede, Alexander M; Montoro, Daniel T; Sinkevicius, Kerstin W; Walton, Zandra E; Barrios, Juliana; Weiss, Daniel J; Camargo, Fernando D; Wong, Kwok-Kin; Kim, Carla F

2014-01-01

Metastasis is the leading cause of morbidity for lung cancer patients. Here we demonstrate that murine tumor propagating cells (TPCs) with the markers Sca1 and CD24 are enriched for metastatic potential in orthotopic transplantation assays. CD24 knockdown decreased the metastatic potential of lung cancer cell lines resembling TPCs. In lung cancer patient data sets, metastatic spread and patient survival could be stratified with a murine lung TPC gene signature. The TPC signature was enriched for genes in the Hippo signaling pathway. Knockdown of the Hippo mediators Yap1 or Taz decreased in vitro cellular migration and transplantation of metastatic disease. Furthermore, constitutively active Yap was sufficient to drive lung tumor progression in vivo. These results demonstrate functional roles for two different pathways, CD24-dependent and Yap/Taz-dependent pathways, in lung tumor propagation and metastasis. This study demonstrates the utility of TPCs for identifying molecules contributing to metastatic lung cancer, potentially enabling the therapeutic targeting of this devastating disease. PMID:24497554

Decrease in pulmonary function and oxygenation after lung resection

PubMed Central

Westerdahl, Elisabeth; Langer, Daniel; Souza, Domingos S.R.; Andreasen, Jan Jesper

2018-01-01

Respiratory deficits are common following curative intent lung cancer surgery and may reduce the patient's ability to be physically active. We evaluated the influence of surgery on pulmonary function, respiratory muscle strength and physical performance after lung resection. Pulmonary function, respiratory muscle strength (maximal inspiratory/expiratory pressure) and 6-min walk test (6MWT) were assessed pre-operatively, 2 weeks post-operatively and 6 months post-operatively in 80 patients (age 68±9 years). Video-assisted thoracoscopic surgery was performed in 58% of cases. Two weeks post-operatively, we found a significant decline in pulmonary function (forced vital capacity −0.6±0.6 L and forced expiratory volume in 1 s −0.43±0.4 L; both p<0.0001), 6MWT (−37.6±74.8 m; p<0.0001) and oxygenation (−2.9±4.7 units; p<0.001), while maximal inspiratory and maximal expiratory pressure were unaffected. At 6 months post-operatively, pulmonary function and oxygenation remained significantly decreased (p<0.001), whereas 6MWT was recovered. We conclude that lung resection has a significant short- and long-term impact on pulmonary function and oxygenation, but not on respiratory muscle strength. Future research should focus on mechanisms negatively influencing post-operative pulmonary function other than impaired respiratory muscle strength. PMID:29362707

Decrease in pulmonary function and oxygenation after lung resection.

PubMed

Brocki, Barbara Cristina; Westerdahl, Elisabeth; Langer, Daniel; Souza, Domingos S R; Andreasen, Jan Jesper

2018-01-01

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

Paraseptal Emphysema: Prevalence and Distribution on CT and Association with Interstitial Lung Abnormalities

PubMed Central

Araki, Tetsuro; Nishino, Mizuki; Zazueta, Oscar E.; Gao, Wei; Dupuis, Josée; Okajima, Yuka; Latourelle, Jeanne C.; Rosas, Ivan O.; Murakami, Takamichi; O’Connor, George T.; Washko, George R.; Hunninghake, Gary M.; Hatabu, Hiroto

2015-01-01

Objective To investigate the prevalence and distribution of paraseptal emphysema on chest CT images in the Framingham Heart Study (FHS) population, and assess its impact on pulmonary function. Also pursued was the association with interstitial lung abnormalities. Materials and Methods We assessed 2633 participants in the FHS for paraseptal emphysema on chest CT. Characteristics of participants, including age, sex, smoking status, clinical symptoms, and results of pulmonary function tests, were compared between those with and without paraseptal emphysema. The association between paraseptal emphysema and interstitial lung abnormalities was investigated. Results Of the 2633 participants, 86 (3%) had pure paraseptal emphysema (defined as paraseptal emphysema with no other subtypes of emphysema other than paraseptal emphysema or a very few centrilobular emphysema involved) in at least one lung zone. The upper zone of the lungs was almost always involved. Compared to the participants without paraseptal emphysema, those with pure paraseptal emphysema were significantly older, and were more frequently male and smokers (mean 64 years, 71% male, mean 36 pack-years, p<0.001) and had significantly decreased FEV1/FVC% (p=0.002), and diffusion capacity of carbon monoxide (DLCO) (p=0.002). There was a significant association between pure paraseptal emphysema and interstitial lung abnormalities (p<0.001). Conclusions The prevalence of pure paraseptal emphysema was 3% in the FHS population, predominantly affects the upper lung zone, and contributes to decreased pulmonary function. Cigarette smoking, aging, and male gender were the factors associated with the presence of paraseptal emphysema. Significant association between paraseptal emphysema and interstitial lung abnormalities was observed. PMID:25868675

Hypergravity Alters the Susceptibility of Cells to Anoxia-Reoxygenation Injury

NASA Technical Reports Server (NTRS)

McCloud, Henry; Pink, Yulondo; Harris-Hooker, Sandra A.; Melhado, Caroline D.; Sanford, Gary L.

1997-01-01

Gravity is a physical force, much like shear stress or mechanical stretch, and should affect organ and cellular function. Researchers have shown that gravity plays a role in ventilation and blood flow distribution, gas exchange, alveolar size and mechanical stresses within the lung. Short exposure to microgravity produced marked alterations in lung blood flow and ventilation distribution while hypergravity exaggerated the regional differences in lung structure and function resulting in reduced ventilation at the base and no ventilation of the upper half of the lung. Microgravity also decreased metabolic activity in cardiac cells, WI-38 embryonic lung cells, and human lymphocytes. Rats, in the tail-suspended head-down tilt model, experienced transient loss of lung water, contrary to an expected increase due to pooling of blood in the pulmonary vasculature. Hypergravity has also been found to increase the proliferation of several different cell lines (e.g., chick embryo fibroblasts) while decreasing cell motility and slowing liver regeneration following partial hepatectomy. These studies show that changes in the gravity environment will affect several aspects of organ and cellular function and produce major change in blood flow and tissue/organ perfusion. However, these past studies have not addressed whether ischemia-reperfusion injury will be exacerbated or ameliorated by changes in the gravity environment, e.g., space flight. Currently, nothing is known about how gravity will affect the susceptibility of different lung and vascular cells to this type of injury. We conducted studies that addressed the following question: Does the susceptibility of lung fibroblasts, vascular smooth muscle, and endothelial cells to anoxia/reoxygenation injury change following exposure to hypergravity conditions?

Responses of Six-Weeks Aquatic Exercise on the Autonomic Nervous System, Peak Nasal Inspiratory Flow and Lung Functions in Young Adults with Allergic Rhinitis.

PubMed

Janyacharoen, Taweesak; Kunbootsri, Narupon; Arayawichanon, Preeda; Chainansamit, Seksun; Sawanyawisuth, Kittisak

2015-06-01

Allergic rhinitis is a chronic respiratory disease. Sympathetic hypofunction is identified in all of the allergic rhinitis patients. Moreover, allergic rhinitis is associated with decreased peak nasal inspiratory flow (PNIF) and impaired lung functions. The aim of this study was to investigate effects of six-week of aquatic exercise on the autonomic nervous system function, PNIF and lung functions in allergic rhinitis patients. Twenty-six allergic rhinitis patients, 12 males and 14 females were recruited in this study. Subjects were diagnosed by a physician based on history, physical examination, and positive reaction to a skin prick test. Subjects were randomly assigned to two groups. The control allergic rhinitis group received education and maintained normal life. The aquatic group performed aquatic exercise for 30 minutes a day, three days a week for six weeks. Heart rate variability, PNIF and lung functions were measured at the beginning, after three weeks and six weeks. There were statistically significant increased low frequency normal units (LF n.u.), PNIF and showed decreased high frequency normal units (HF n.u.) at six weeks after aquatic exercise compared with the control group. Six weeks of aquatic exercise could increase sympathetic activity and PNIF in allergic rhinitis patients.

Analysis of effect of the solubility on gas exchange in nonhomogeneous lungs

NASA Technical Reports Server (NTRS)

Colburn, W. E., Jr.; Evans, J. W.; West, J. B.

1974-01-01

A comparison is made of the gas exchange in nonhomogeneous lung models and in homogeneous lung models with the same total blood flow and ventilation. It is shown that the ratio of the rate of gas transfer of the inhomogeneous lung model over the rate of gas transfer of the homogeneous lung model as a function of gas solubility always has the qualitative features for gases with linear dissociation curves. This ratio is 1 for a gas with zero solubility and decreases to a single minimum. It subsequently rises to approach 1 as the solubility tends to infinity. The early portion of the graph of this function is convex, then after a single inflection point it is concave.

The association between anthropometric measures and lung function in a population-based study of Canadian adults.

PubMed

Rowe, A; Hernandez, P; Kuhle, S; Kirkland, S

2017-10-01

Decreased lung function has health impacts beyond diagnosable lung disease. It is therefore important to understand the factors that may influence even small changes in lung function including obesity, physical fitness and physical activity. The aim of this study was to determine the anthropometric measure most useful in examining the association with lung function and to determine how physical activity and physical fitness influence this association. The current study used cross-sectional data on 4662 adults aged 40-79 years from the Canadian Health Measures Survey Cycles 1 and 2. Linear regression models were used to examine the association between the anthropometric and lung function measures (forced expiratory volume in 1 s [FEV 1 ] and forced vital capacity [FVC]); R 2 values were compared among models. Physical fitness and physical activity terms were added to the models and potential confounding was assessed. Models using sum of 5 skinfolds and waist circumference consistently had the highest R 2 values for FEV 1 and FVC, while models using body mass index consistently had among the lowest R 2 values for FEV 1 and FVC and for men and women. Physical activity and physical fitness were confounders of the relationships between waist circumference and the lung function measures. Waist circumference remained a significant predictor of FVC but not FEV 1 after adjustment for physical activity or physical fitness. Waist circumference is an important predictor of lung function. Physical activity and physical fitness should be considered as potential confounders of the relationship between anthropometric measures and lung function. Copyright © 2017. Published by Elsevier Ltd.

[Testing and analyzing the lung functions in the normal population in Hebei province].

PubMed

Chen, Li; Zhao, Ming; Han, Shao-mei; Li, Zhong-ming; Zhu, Guang-jin

2004-08-01

To investigate the lung function of the normal subjects living in Hebei province and its correlative factors such as living circumstance, age, height, and body weight. The lung volumes and breath capacities of 1,587 normal subjects were tested by portable spirometers (Scope Rotry) from August to October in 2002. The influences of living circumstance, age, gender, height, and body weight on lung functions were observed and analyzed. No significant difference was found between urban and rural areas in all indexes (P > 0.05); however, significant difference existed between male and female subjects (P = 0.000). The change trends of lung function in male and female subjects were similar. Growth spurt appeared at the age of 12-16 years in male subjects and 12-14 years in female subjects. Vital capacity (VC), forced vital capacity (FVC), and forced expiratory volume in one second (FEV1) reached their peaks at the age of 26-34 years and then decreased with age. Peak expiratory flow (PEF), 25% forced expiratory flow (FEF50%), and 75% forced expiratory flow (FEF75%) appeared at the age of 18 and then went down with age. Both height and weight had a correlation with all the indexes of lung functions, although the influence of height is stronger than weight. All the indexes of lung function have correlations with age, height, and weight. Lung function changes with aging, therefore different expected values shall be available for the adolescence, young adults, and middle-aged and old people. This study provides reference values of lung function for normal population.

Postoperative complications do not influence the pattern of early lung function recovery after lung resection for lung cancer in patients at risk

PubMed Central

2014-01-01

Background The pattern and factors influencing the lung function recovery in the first postoperative days are still not fully elucidated, especially in patients at increased risk. Methods Prospective study on 60 patients at increased risk, who underwent a lung resection for primary lung cancer. Inclusion criteria: complete resection and one or more known risk factors in form of COPD, cardiovascular disorders, advanced age or other comorbidities. Previous myocardial infarction, myocardial revascularization or stenting, cardiac rhythm disorders, arterial hypertension and myocardiopathy determined the increased cardiac risk. The severity of COPD was graded according to GOLD criteria. The trend of the postoperative lung function recovery was assessed by performing spirometry with a portable spirometer. Results Cardiac comorbidity existed in 55%, mild and moderate COPD in 20% and 35% of patients respectively. Measured values of FVC% and FEV1% on postoperative days one, three and seven, showed continuous improvement, with significant difference between the days of measurement, especially between days three and seven. There was no difference in the trend of the lung function recovery between patients with and without postoperative complications. Whilst pO2 was decreasing during the first three days in a roughly parallel fashion in patients with respiratory, surgical complications and in patients without complications, a slight hypercapnia registered on the first postoperative day was gradually abolished in all groups except in patients with cardiac complications. Conclusion Extent of the lung resection and postoperative complications do not significantly influence the trend of the lung function recovery after lung resection for lung cancer. PMID:24884793

Postoperative complications do not influence the pattern of early lung function recovery after lung resection for lung cancer in patients at risk.

PubMed

Ercegovac, Maja; Subotic, Dragan; Zugic, Vladimir; Jakovic, Radoslav; Moskovljevic, Dejan; Bascarevic, Slavisa; Mujovic, Natasa

2014-05-19

The pattern and factors influencing the lung function recovery in the first postoperative days are still not fully elucidated, especially in patients at increased risk. Prospective study on 60 patients at increased risk, who underwent a lung resection for primary lung cancer. complete resection and one or more known risk factors in form of COPD, cardiovascular disorders, advanced age or other comorbidities. Previous myocardial infarction, myocardial revascularization or stenting, cardiac rhythm disorders, arterial hypertension and myocardiopathy determined the increased cardiac risk. The severity of COPD was graded according to GOLD criteria. The trend of the postoperative lung function recovery was assessed by performing spirometry with a portable spirometer. Cardiac comorbidity existed in 55%, mild and moderate COPD in 20% and 35% of patients respectively. Measured values of FVC% and FEV1% on postoperative days one, three and seven, showed continuous improvement, with significant difference between the days of measurement, especially between days three and seven. There was no difference in the trend of the lung function recovery between patients with and without postoperative complications. Whilst pO2 was decreasing during the first three days in a roughly parallel fashion in patients with respiratory, surgical complications and in patients without complications, a slight hypercapnia registered on the first postoperative day was gradually abolished in all groups except in patients with cardiac complications. Extent of the lung resection and postoperative complications do not significantly influence the trend of the lung function recovery after lung resection for lung cancer.

Inspiratory and expiratory computed tomographic volumetry for lung volume reduction surgery.

PubMed

Morimura, Yuki; Chen, Fengshi; Sonobe, Makoto; Date, Hiroshi

2013-06-01

Three-dimensional (3D) computed tomographic (CT) volumetry has been introduced into the field of thoracic surgery, and a combination of inspiratory and expiratory 3D-CT volumetry provides useful data on regional pulmonary function as well as the volume of individual lung lobes. We report herein a case of a 62-year-old man with severe emphysema who had undergone lung volume reduction surgery (LVRS) to assess this technique as a tool for the evaluation of regional lung function and volume before and after LVRS. His postoperative pulmonary function was maintained in good condition despite a gradual slight decrease 2 years after LVRS. This trend was also confirmed by a combination of inspiratory and expiratory 3D-CT volumetry. We confirm that a combination of inspiratory and expiratory 3D-CT volumetry might be effective for the preoperative assessment of LVRS in order to determine the amount of lung tissue to be resected as well as for postoperative evaluation. This novel technique could, therefore, be used more widely to assess local lung function.

Inspiratory and expiratory computed tomographic volumetry for lung volume reduction surgery

PubMed Central

Morimura, Yuki; Chen, Fengshi; Sonobe, Makoto; Date, Hiroshi

2013-01-01

Three-dimensional (3D) computed tomographic (CT) volumetry has been introduced into the field of thoracic surgery, and a combination of inspiratory and expiratory 3D-CT volumetry provides useful data on regional pulmonary function as well as the volume of individual lung lobes. We report herein a case of a 62-year-old man with severe emphysema who had undergone lung volume reduction surgery (LVRS) to assess this technique as a tool for the evaluation of regional lung function and volume before and after LVRS. His postoperative pulmonary function was maintained in good condition despite a gradual slight decrease 2 years after LVRS. This trend was also confirmed by a combination of inspiratory and expiratory 3D-CT volumetry. We confirm that a combination of inspiratory and expiratory 3D-CT volumetry might be effective for the preoperative assessment of LVRS in order to determine the amount of lung tissue to be resected as well as for postoperative evaluation. This novel technique could, therefore, be used more widely to assess local lung function. PMID:23460599

Quantitative evaluation of native lung hyperinflation after single lung transplantation for emphysema using three-dimensional computed tomography volumetry.

PubMed

Motoyama, H; Chen, F; Ohsumi, A; Hijiya, K; Takahashi, M; Ohata, K; Yamada, T; Sato, M; Aoyama, A; Bando, T; Date, H

2014-04-01

Although double lung transplantation is performed more frequently for emphysema, single lung transplantation (SLT) continues to be performed owing to limited donor organ availability. Native lung hyperinflation (NLH) is a unique complication following SLT for emphysema. Three-dimensional computed tomography (3D-CT) volumetry has been introduced into the field of lung transplantation, which we used to assess NLH in emphysema patients undergoing SLT. The primary purpose of this study was to confirm the effectiveness of 3D-CT volumetry in the evaluation of NLH following SLT for emphysema. In 5 emphysema patients undergoing SLT at Kyoto University Hospital, 3D-CT volumetry data, pulmonary function test results, and clinical and radiological findings were retrospectively evaluated. Three patients did not develop a significant mediastinal shift, whereas the other 2 patients developed a mediastinal shift. In the 3 patients without a mediastinal shift, 3D-CT volumetry did not show a significant increase in native lung volume. These patients had a history of sternotomy prior to lung transplantation and firm adhesion on the mediastinal side was detected during lung transplantation. One of 2 patients with a mediastinal shift developed severe dyspnea with significantly decreased pulmonary function, and 3D-CT volumetry showed a significant increase in the native lung volume. However, the other patient did not show any dyspnea and his native lung volume decreased postoperatively (preoperatively to 6 months postoperatively: +981 mL and -348 mL, respectively). Although bilateral lung transplantation has become preferable for emphysema patients owing to postoperative NLH with SLT, patients with a history of sternotomy prior to lung transplantation might be good candidates for SLT. 3D-CT volumetry may be a useful method for detection of NLH. Copyright © 2014 Elsevier Inc. All rights reserved.

Alterations in NO- and PGI2- dependent function in aorta in the orthotopic murine model of metastatic 4T1 breast cancer: relationship with pulmonary endothelial dysfunction and systemic inflammation.

PubMed

Buczek, E; Denslow, A; Mateuszuk, L; Proniewski, B; Wojcik, T; Sitek, B; Fedorowicz, A; Jasztal, A; Kus, E; Chmura-Skirlinska, A; Gurbiel, R; Wietrzyk, J; Chlopicki, S

2018-05-22

Patients with cancer develop endothelial dysfunction and subsequently display a higher risk of cardiovascular events. The aim of the present work was to examine changes in nitric oxide (NO)- and prostacyclin (PGI 2 )-dependent endothelial function in the systemic conduit artery (aorta), in relation to the formation of lung metastases and to local and systemic inflammation in a murine orthotopic model of metastatic breast cancer. BALB/c female mice were orthotopically inoculated with 4T1 breast cancer cells. Development of lung metastases, lung inflammation, changes in blood count, systemic inflammatory response (e.g. SAA, SAP and IL-6), as well as changes in NO- and PGI 2 -dependent endothelial function in the aorta, were examined 2, 4, 5 and 6 weeks following cancer cell transplantation. As early as 2 weeks following transplantation of breast cancer cells, in the early metastatic stage, lungs displayed histopathological signs of inflammation, NO production was impaired and nitrosylhemoglobin concentration in plasma was decreased. After 4 to 6 weeks, along with metastatic development, progressive leukocytosis and systemic inflammation (as seen through increased SAA, SAP, haptoglobin and IL-6 plasma concentrations) were observed. Six weeks following cancer cell inoculation, but not earlier, endothelial dysfunction in aorta was detected; this involved a decrease in basal NO production and a decrease in NO-dependent vasodilatation, that was associated with a compensatory increase in cyclooxygenase-2 (COX-2)- derived PGI 2 production. In 4 T1 metastatic breast cancer in mice early pulmonary metastasis was correlated with lung inflammation, with an early decrease in pulmonary as well as systemic NO availability. Late metastasis was associated with robust, cancer-related, systemic inflammation and impairment of NO-dependent endothelial function in the aorta that was associated with compensatory upregulation of the COX-2-derived PGI 2 pathway.

The Influence of Large-Scale Airborne Particle Decline and Traffic-Related Exposure on Children’s Lung Function

PubMed Central

Sugiri, Dorothea; Ranft, Ulrich; Schikowski, Tamara; Krämer, Ursula

2006-01-01

Between 1991 and 2000, ambient air pollution in East Germany changed to resemble West German pollution levels: The concentration of total suspended particles (TSPs) decreased on a broad scale while traffic increased. During that time, we analyzed total lung capacity (TLC) and airway resistance (Raw) of East and West German children. We tested children 5–7 years of age (n = 2,574) with cooperation-independent body plethysmography in repeated cross sections. We used random-effect models to determine the mutually adjusted association between lung function and short-term and chronic particle exposure and its interaction with living near a busy road. Annual averages of TSPs declined from 77 to 44 μg/m3; averages on the day of investigation declined from 133 to 30 μg/m3. Differences in lung function between East and West German children vanished during the investigation time. The association of TSPs with Raw and TLC was stronger in children living > 50 m away from busy roads. East German children from this group had an Raw 2.5% higher [95% confidence interval (CI), 0.0–5.1%] per 40-μg/m3 increase of daily TSP averages. TLC decreased by 6.2% (95% CI, 0.04–11.6%) per 40-μg/m3 increase in annual mean TSPs, and this effect was equally pronounced in East and West Germany. TSP exposure decreased on a broad scale between 1991 and 2000. Lower concentrations of TSPs were associated with better measures of lung function in 6-year-old children. For children living near busy roads, this effect was diminished. PMID:16451868

Experimental evidence of age-related adaptive changes in human acinar airways

PubMed Central

Quirk, James D.; Sukstanskii, Alexander L.; Woods, Jason C.; Lutey, Barbara A.; Conradi, Mark S.; Gierada, David S.; Yusen, Roger D.; Castro, Mario

2015-01-01

The progressive decline of lung function with aging is associated with changes in lung structure at all levels, from conducting airways to acinar airways (alveolar ducts and sacs). While information on conducting airways is becoming available from computed tomography, in vivo information on the acinar airways is not conventionally available, even though acini occupy 95% of lung volume and serve as major gas exchange units of the lung. The objectives of this study are to measure morphometric parameters of lung acinar airways in living adult humans over a broad range of ages by using an innovative MRI-based technique, in vivo lung morphometry with hyperpolarized 3He gas, and to determine the influence of age-related differences in acinar airway morphometry on lung function. Pulmonary function tests and MRI with hyperpolarized 3He gas were performed on 24 healthy nonsmokers aged 19-71 years. The most significant age-related difference across this population was a 27% loss of alveolar depth, h, leading to a 46% increased acinar airway lumen radius, hence, decreased resistance to acinar air transport. Importantly, the data show a negative correlation between h and the pulmonary function measures forced expiratory volume in 1 s and forced vital capacity. In vivo lung morphometry provides unique information on age-related changes in lung microstructure and their influence on lung function. We hypothesize that the observed reduction of alveolar depth in subjects with advanced aging represents a remodeling process that might be a compensatory mechanism, without which the pulmonary functional decline due to other biological factors with advancing age would be significantly larger. PMID:26542518

H2O2 sensors of lungs and blood vessels and their role in the antioxidant defense of the body.

PubMed

Skulachev, V P

2001-10-01

This paper considers the composition and function of sensory systems monitoring H2O2 level by the lung neuroepithelial cells and carotid bodies. These systems are localized in the plasma membrane of the corresponding cells and are composed of (O2*-)-generating NADPH-oxidase and an H2O2-activated K+ channel. This complex structure of the H2O2 sensors is probably due to their function in antioxidant defense. By means of these sensors, an increase in the H2O2 level in lung or blood results in a decrease in lung ventilation and constriction of blood vessels. This action lowers the O2 flux to the tissues and, hence, intracellular [O2]. The [O2] decrease, in turn, inhibits intracellular generation of reactive oxygen species. The possible roles of such systems under normal conditions (e.g., the effect of O2*- in air) and in some pathologies (e.g., pneumonia) is discussed.

Pulmonary function test in traffic police personnel in Pondicherry.

PubMed

Pal, Pravati; John, Robert A; Dutta, T K; Pal, G K

2010-01-01

Traffic policemen working in the busy traffic signal areas get exposed to the vehicular emissions for years together. The fumes, chemicals and particles present in the emission are reported to be damaging to the lung functions of these individuals. Since there were no data available on the PFT parameters of traffic police personnel of Pondicherry, this study was taken up to assess the effect of traffic air pollution on their pulmonary functions. PFT parameters were recorded in age- and BMI-matched 30 traffic police personnel (study group) and 30 general police personnel (control group) of male gender. As chronic smoking is known to be a critical factor in altering lung function, PFT parameters were compared between the smokers as well as nonsmokers of both the groups. In nonsmokers, there was significant decrease in VC (P < 0.05), FEV1 (P < 0.01), FEF-25 (P < 0.05) and PIF (P < 0.05) in study group compared to the control group. In smokers, there was significant decrease in VC (P < 0.05), FEV1 (P <00001), PEF (P < 0.0001), MVV (P < 0.0001), FEF-25 (P < 0.0001), and PIF (P < 0.01) in study group compared to the control group. These changes indicate restriction to the lung expansion, obstruction and narrowing of the airways in traffic police personnel compared to the general police personnel. This may be due to exposure to vehicular pollution for several hours in a day for many years causing decreased functional capacity of the lungs and chronic smoking worsens the condition.

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

PubMed

Belmaati, Esther Okeke; Iversen, Martin; Kofoed, Klaus F; Nielsen, Michael B; Mortensen, Jann

2012-06-01

Scintigraphy has been used as a tool to detect dysfunction of the lung before and after transplantation. The aims of this study were to evaluate the development of the ventilation-perfusion relationships in single lung transplant recipients in the first year, at 3 months after transplantation, and to investigate whether scintigraphic findings at 3 months were predictive for the outcome at 12 months in relation to primary graft dysfunction (PGD) and lung function. A retrospective study was carried out on all patients who prospectively and consecutively were referred for a routine lung scintigraphy procedure 3 months after single lung transplantation (SLTX). A total of 41 patients were included in the study: 20 women and 21 men with the age span of patients at transplantation being 38-66 years (mean ± SD: 54.2 ± 6.0). Patient records also included lung function tests and chest X-ray images. We found no significant correlation between lung function distribution at 3 months and PGD at 72 h. There was also no significant correlation between PGD scores at 72 h and lung function at 6 and 12 months. The same applied to scintigraphic scores for heterogeneity at 3 months compared with lung function at 6 and 12 months. Fifty-five percent of all patients had decreased ventilation function measured in the period from 6 to 12 months. Forty-nine percent of the patients had normal perfusion evaluations, and 51% had abnormal perfusion evaluations at 3 months. For ventilation evaluations, 72% were normal and 28% were abnormal. There was a significant difference in the normal versus abnormal perfusion and ventilation scintigraphic images evaluated from the same patients. Ventilation was distributed more homogenously in the transplanted lung than perfusion in the same lung. The relative distribution of perfusion and ventilation to the transplanted lung of patients with and without a primary diagnosis of fibrosis did not differ significantly from each other. We conclude that PGD defined at 72 h does not lead to recognizable changes in ventilation-perfusion scintigrapy at 3 months, and scintigraphic findings do not correlate with development in lung function in the first 12 months.

Cigarette smoking and pulmonary diffusion defects in rheumatoid arthritis.

PubMed

Westedt, M L; Hazes, J M; Breedveld, F C; Sterk, P J; Dijkman, J H

1998-01-01

The pathogenesis of lung disease in rheumatoid arthritis (RA) has still to be defined. Risk factors associated with lung involvement in RA were investigated by means of pulmonary function studies in 40 RA patients without apparent lung disease. A decreased carbon monoxide (CO) diffusion capacity indicative of interstitial lung disease (ILD) was the main pulmonary function defect found in the first 20 patients. The occurrence was associated with current cigarette smoking. This association was confirmed in a case control study performed subsequently. These data suggest that ILD in RA is stimulated by smoking and provide an additional argument that modification of smoking behaviour in RA patients might lead to less severe complications.

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

In utero and early childhood exposure to arsenic decreases lung function in children.

PubMed

Recio-Vega, Rogelio; Gonzalez-Cortes, Tania; Olivas-Calderon, Edgar; Lantz, R Clark; Gandolfi, A Jay; Gonzalez-De Alba, Cesar

2015-04-01

The lung is a target organ for adverse health outcomes following exposure to As. Several studies have reported a high prevalence of respiratory symptoms and diseases in subjects highly exposed to As 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 As and its metabolites with lung function in children exposed in utero and in early childhood to high As levels through drinking water. A total of 358 healthy children were included in our study. Individual exposure was assessed based on urinary concentration of inorganic As. Lung function was assessed by spirometry. Participants were exposed since pregnancy until early childhood to an average water As concentration of 152.13 µg l⁻¹. The mean urinary As level registered in the studied subjects was 141.2 µg l⁻¹ 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 percentage of inorganic As. 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. Exposure to As through drinking water during in utero and early life was associated with a decrease in forced vital capacity and with a restrictive spirometric pattern in the children evaluated. Copyright © 2014 John Wiley & Sons, Ltd.

A portable single-sided magnet system for remote NMR measurements of pulmonary function.

PubMed

Dabaghyan, Mikayel; Muradyan, Iga; Hrovat, Alan; Butler, James; Frederick, Eric; Zhou, Feng; Kyriazis, Angelos; Hardin, Charles; Patz, Samuel; Hrovat, Mirko

2014-12-01

In this work, we report initial results from a light-weight, low field magnetic resonance device designed to make relative pulmonary density measurements at the bedside. The development of this device necessarily involves special considerations for the magnet, RF and data acquisition schemes as well as a careful analysis of what is needed to provide useful information in the ICU. A homogeneous field region is created remotely from the surface of the magnet such that when the magnet is placed against the chest, an NMR signal is measured from a small volume in the lung. In order to achieve portability, one must trade off field strength and therefore spatial resolution. We report initial measurements from a ping-pong ball size region in the lung as a function of lung volume. As expected, we measured decreased signal at larger lung volumes since lung density decreases with increasing lung volume. Using a CPMG sequence with ΔTE=3.5 ms and a 20 echo train, a signal to noise ratio ~1100 was obtained from an 8.8mT planar magnet after signal averaging for 43 s. This is the first demonstration of NMR measurements made on a human lung with a light-weight planar NMR device. We argue that very low spatial resolution measurements of different lobar lung regions will provide useful diagnostic information for clinicians treating Acute Respiratory Distress Syndrome as clinicians want to avoid ventilator pressures that cause either lung over distension (too much pressure) or lung collapse (too little pressure). Copyright © 2014 John Wiley & Sons, Ltd.

A portable single-sided magnet system for remote NMR measurements of pulmonary function

PubMed Central

Mikayel, Dabaghyan; Iga, Muradyan; James, Butler; Eric, Frederick; Feng, Zhou; Angelos, Kyriazis; Charles, Hardin; Samuel, Patz; Mirko, Hrovat

2014-01-01

In this work, we report initial results from a light-weight, low field magnetic resonance device designed to make relative pulmonary density measurements at the bedside. The development of this device necessarily involves special considerations for the magnet, RF and data acquisition schemes as well as a careful analysis of what is needed to provide useful information in the ICU. A homogeneous field region is created remotely from the surface of the magnet such that when the magnet is placed against the chest, an NMR signal is measured from a small volume in the lung. In order to achieve portability, one must trade off field strength and therefore spatial resolution. We report initial measurements from a ping-pong ball size region in the lung as a function of lung volume. As expected, we measured decreased signal at larger lung volumes since lung density decreases with increasing lung volume. Using a CPMG sequence with ΔTE=3.5 ms and a 20 echo train, a signal to noise ratio ~1100 was obtained from an 8.8mT planar magnet after signal averaging for 43 s. This is the first demonstration of NMR measurements made on a human lung with a light-weight planar NMR device. We argue that very low spatial resolution measurements of different lobar lung regions will provide useful diagnostic information for clinicians treating Acute Respiratory Distress Syndrome as clinicians want to avoid ventilator pressures that cause either lung over distension (too much pressure) or lung collapse (too little pressure). PMID:24953556

Is Chronic Obstructive Pulmonary Disease an Accelerated Aging Disease?

PubMed

MacNee, William

2016-12-01

Aging is one of the most important risk factors for most chronic diseases. The worldwide increase in life expectancy has been accompanied by an increase in the prevalence of age-related diseases that result in significant morbidity and mortality and place an enormous burden on healthcare and resources. Aging is a progressive degeneration of the tissues that has a negative impact on the structure and function of vital organs. The lung ages, resulting in decreased function and reduced capacity to respond to environmental stresses and injury. Many of the changes that occur in the lungs with normal aging, such as decline in lung function, increased gas trapping, loss of lung elastic recoil, and enlargement of the distal air spaces, also are present in chronic obstructive pulmonary disease (COPD). The prevalence of COPD is two to three times higher in people over the age of 60 years than in younger age groups. Indeed, COPD has been considered a condition of accelerated lung aging. Several mechanisms associated with aging are present in the lungs of patients with COPD. Cell senescence is present in emphysematous lungs and is associated with shortened telomeres and decreased antiaging molecules, suggesting accelerated aging in the lungs of patients with COPD. Increasing age leads to elevated basal levels of inflammation and oxidative stress (inflammaging) and to increased immunosenescence associated with changes in both the innate and adaptive immune responses. These changes are similar to those that occur in COPD and may enhance the activity of the disease as well as increase susceptibility to exacerbations in patients with COPD. Understanding the mechanism of age-related changes in COPD may identify novel therapies for this condition.

Microbiota Promotes Chronic Pulmonary Inflammation by Enhancing IL-17A and Autoantibodies.

PubMed

Yadava, Koshika; Pattaroni, Céline; Sichelstiel, Anke K; Trompette, Aurélien; Gollwitzer, Eva S; Salami, Olawale; von Garnier, Christophe; Nicod, Laurent P; Marsland, Benjamin J

2016-05-01

Changes in the pulmonary microbiota are associated with progressive respiratory diseases including chronic obstructive pulmonary disease (COPD). Whether there is a causal relationship between these changes and disease progression remains unknown. To investigate the link between an altered microbiota and disease, we used a murine model of chronic lung inflammation that is characterized by key pathological features found in COPD and compared responses in specific pathogen-free (SPF) mice and mice depleted of microbiota by antibiotic treatment or devoid of a microbiota (axenic). Mice were challenged with LPS/elastase intranasally over 4 weeks, resulting in a chronically inflamed and damaged lung. The ensuing cellular infiltration, histological damage, and decline in lung function were quantified. Similar to human disease, the composition of the pulmonary microbiota was altered in diseased animals. We found that the microbiota richness and diversity were decreased in LPS/elastase-treated mice, with an increased representation of the genera Pseudomonas and Lactobacillus and a reduction in Prevotella. Moreover, the microbiota was implicated in disease development as mice depleted, or devoid, of microbiota exhibited an improvement in lung function, reduced inflammation, and lymphoid neogenesis. The absence of microbial cues markedly decreased the production of IL-17A, whereas intranasal transfer of fluid enriched with the pulmonary microbiota isolated from diseased mice enhanced IL-17A production in the lungs of antibiotic-treated or axenic recipients. Finally, in mice harboring a microbiota, neutralizing IL-17A dampened inflammation and restored lung function. Collectively, our data indicate that host-microbial cross-talk promotes inflammation and could underlie the chronicity of inflammatory lung diseases.

Quantitative assessment of lung ventilation and microstructure in an animal model of idiopathic pulmonary fibrosis using hyperpolarized gas MRI.

PubMed

Stephen, Michael J; Emami, Kiarash; Woodburn, John M; Chia, Elaine; Kadlecek, Stephen; Zhu, Jianliang; Pickup, Stephen; Ishii, Masaru; Rizi, Rahim R; Rossman, Milton

2010-11-01

The use of hyperpolarized (3)He magnetic resonance imaging as a quantitative lung imaging tool has progressed rapidly in the past decade, mostly in the assessment of the airway diseases chronic obstructive pulmonary disease and asthma. This technique has shown potential to assess both structural and functional information in healthy and diseased lungs. In this study, the regional measurements of structure and function were applied to a bleomycin rat model of interstitial lung disease. Male Sprague-Dawley rats (weight, 300-350 g) were administered intratracheal bleomycin. After 3 weeks, apparent diffusion coefficient and fractional ventilation were measured by (3)He magnetic resonance imaging and pulmonary function testing using a rodent-specific plethysmography chamber. Sensitized and healthy animals were then compared using threshold analysis to assess the potential sensitivity of these techniques to pulmonary abnormalities. No significant changes were observed in total lung volume and compliance between the two groups. Airway resistance elevated and forced expiratory volume significantly declined in the 3-week bleomycin rats, and fractional ventilation was significantly decreased compared to control animals (P < .0004). The apparent diffusion coefficient of (3)He showed a smaller change but still a significant decrease in 3-week bleomycin animals (P < .05). Preliminary results suggest that quantitative (3)He magnetic resonance imaging can be a sensitive and noninvasive tool to assess changes in an animal interstitial lung disease model. This technique may be useful for longitudinal animal studies and also in the investigation of human interstitial lung diseases. Copyright © 2010 AUR. Published by Elsevier Inc. All rights reserved.

Improved pulmonary function in the nitrofen model of congenital diaphragmatic hernia following prenatal maternal dexamethasone and/or sildenafil.

PubMed

Burgos, Carmen Mesas; Pearson, Erik G; Davey, Marcus; Riley, John; Jia, Huimin; Laje, Pablo; Flake, Alan W; Peranteau, William H

2016-10-01

Pulmonary hypoplasia and hypertension is a leading cause of morbidity and mortality in congenital diaphragmatic hernia (CDH). The etiologic insult occurs early in gestation highlighting the potential of prenatal interventions. We evaluated prenatal pharmacologic therapies in the nitrofen CDH model. Olive oil or nitrofen were administered alone or with dexamethasone (DM), sildenafil, or DM+sildenafil to pregnant rats. Newborn pups were assessed for lung function, structure and pulmonary artery (PA) flow and resistance. Prenatal DM treatment of CDH pups increased alveolar volume density (Vva), decreased interalveloar septal thickness, increased tidal volumes and improved ventilation without improving oxygenation or PA resistance. Sildenafil decreased PA resistance and improved oxygenation without improving ventilation or resulting in significant histologic changes. DM+sildenafil decreased PA resistance, improved oxygenation and ventilation while increasing Vva and decreasing interalveolar septal and pulmonary arteriole medial wall thickness. Lung and body weights were decreased in pups treated with DM and/or sildenafil. Prenatal DM or sildenafil treatment increased pulmonary compliance and decreased pulmonary vascular resistance respectively, and was associated with improved neonatal gas exchange but had a detrimental effect on lung and fetal growth. This study highlights the potential of individual and combined prenatal pharmacologic therapies for CDH management.

Evaluation of visual and computer-based CT analysis for the identification of functional patterns of obstruction and restriction in hypersensitivity pneumonitis.

PubMed

Jacob, Joseph; Bartholmai, Brian J; Brun, Anne Laure; Egashira, Ryoko; Rajagopalan, Srinivasan; Karwoski, Ronald; Kouranos, Vasileios; Kokosi, Maria; Hansell, David M; Wells, Athol U

2017-11-01

To determine whether computer-based quantification (CALIPER software) is superior to visual computed tomography (CT) scoring in the identification of CT patterns indicative of restrictive and obstructive functional indices in hypersensitivity pneumonitis (HP). A total of 135 consecutive HP patients had CT parenchymal patterns evaluated quantitatively by both visual scoring and CALIPER. Results were evaluated against: forced vital capacity (FVC), total lung capacity (TLC), diffusing capacity for carbon monoxide (DL CO ) and a composite physiological index (CPI) to identify which CT scoring method better correlated with functional indices. CALIPER-derived scores of total interstitial lung disease extent correlated more strongly than visual scores: FVC (CALIPER R = 0.73, visual R = 0.51); DL CO (CALIPER R = 0.61, visual R = 0.48); and CPI (CALIPER R = 0·70, visual R = 0·55). The CT variable that correlated most strongly with restrictive functional indices was CALIPER pulmonary vessel volume (PVV): FVC R = 0.75, DL CO R = 0.68 and CPI R = 0.76. Ground-glass opacity quantified by CALIPER alone demonstrated strong associations with restrictive functional indices: CALIPER FVC R = 0.65; DL CO R = 0.59; CPI R = 0.64; and visual = not significant. Decreased attenuation lung quantified by CALIPER was a better morphological measure of obstructive lung disease than equivalent visual scores as judged by relationships with TLC (CALIPER R = 0.63 and visual R = 0.12). All results were maintained on multivariate analysis. CALIPER improved on visual scoring in HP as judged by restrictive and obstructive functional correlations. Decreased attenuation regions of the lung quantified by CALIPER demonstrated better linkages to obstructive lung physiology than visually quantified CT scores. A novel CALIPER variable, the PVV, demonstrated the strongest linkages with restrictive functional indices and could represent a new automated index of disease severity in HP. © 2017 Asian Pacific Society of Respirology.

miR-448 is a novel prognostic factor of lung squamous cell carcinoma and regulates cells growth and metastasis by targeting DCLK1.

PubMed

Shan, Changting; Fei, Fan; Li, Fengzhu; Zhuang, Bo; Zheng, Yulong; Wan, Yufeng; Chen, Jianhui

2017-05-01

MicroRNA-448 (miR-448) has been showed to be low-expressed and function as tumor suppressor in most human cancers. However, there are limited reports on the clinical significance and biological function of miR-448 in lung squamous cell carcinoma. In this study, we observed that miR-448 expression was decreased in lung squamous cell carcinoma tissues and cell lines. Meanwhile, miR-448 expression associated with differentiated degree, T classification (tumor size), N classification (lymph node metastasis), M classification (distant metastasis), clinical stage and prognosis of lung squamous cell carcinoma patients. In survival analysis, low expression of miR-448 was a poor independent prognostic factor for lung squamous cell carcinoma patients. Moreover, gain-of-function and loss-of-function studies showed miR-448 acted as a tumor suppressor regulating lung squamous cell carcinoma cells growth and metastasis. Furthermore, DCLK1 has been identified as a potential target for miR-448 to regulate lung squamous cell carcinoma cells growth and metastasis. In conclusion, miR-448 low-expression was a poor prognostic factor for lung squamous cell carcinoma patients, and miR-448 served as a tumor suppressor in lung squamous cell carcinoma cells via targeting DCLK1. Copyright © 2017. Published by Elsevier Masson SAS.

Progressive Vascular Functional and Structural Damage in a Bronchopulmonary Dysplasia Model in Preterm Rabbits Exposed to Hyperoxia.

PubMed

Jiménez, Julio; Richter, Jute; Nagatomo, Taro; Salaets, Thomas; Quarck, Rozenn; Wagennar, Allard; Wang, Hongmei; Vanoirbeek, Jeroen; Deprest, Jan; Toelen, Jaan

2016-10-24

Bronchopulmonary dysplasia (BPD) is caused by preterm neonatal lung injury and results in oxygen dependency and pulmonary hypertension. Current clinical management fails to reduce the incidence of BPD, which calls for novel therapies. Fetal rabbits have a lung development that mimics humans and can be used as a translational model to test novel treatment options. In preterm rabbits, exposure to hyperoxia leads to parenchymal changes, yet vascular damage has not been studied in this model. In this study we document the early functional and structural changes of the lung vasculature in preterm rabbits that are induced by hyperoxia after birth. Pulmonary artery Doppler measurements, micro-CT barium angiograms and media thickness of peripheral pulmonary arteries were affected after seven days of hyperoxia when compared to controls. The parenchyma was also affected both at the functional and structural level. Lung function testing showed higher tissue resistance and elastance, with a decreased lung compliance and lung capacity. Histologically hyperoxia leads to fewer and larger alveoli with thicker walls, less developed distal airways and more inflammation than normoxia. In conclusion, we show that the rabbit model develops pulmonary hypertension and developmental lung arrest after preterm lung injury, which parallel the early changes in human BPD. Thus it enables the testing of pharmaceutical agents that target the cardiovascular compartment of the lung for further translation towards the clinic.

Progressive Vascular Functional and Structural Damage in a Bronchopulmonary Dysplasia Model in Preterm Rabbits Exposed to Hyperoxia

PubMed Central

Jiménez, Julio; Richter, Jute; Nagatomo, Taro; Salaets, Thomas; Quarck, Rozenn; Wagennar, Allard; Wang, Hongmei; Vanoirbeek, Jeroen; Deprest, Jan; Toelen, Jaan

2016-01-01

Bronchopulmonary dysplasia (BPD) is caused by preterm neonatal lung injury and results in oxygen dependency and pulmonary hypertension. Current clinical management fails to reduce the incidence of BPD, which calls for novel therapies. Fetal rabbits have a lung development that mimics humans and can be used as a translational model to test novel treatment options. In preterm rabbits, exposure to hyperoxia leads to parenchymal changes, yet vascular damage has not been studied in this model. In this study we document the early functional and structural changes of the lung vasculature in preterm rabbits that are induced by hyperoxia after birth. Pulmonary artery Doppler measurements, micro-CT barium angiograms and media thickness of peripheral pulmonary arteries were affected after seven days of hyperoxia when compared to controls. The parenchyma was also affected both at the functional and structural level. Lung function testing showed higher tissue resistance and elastance, with a decreased lung compliance and lung capacity. Histologically hyperoxia leads to fewer and larger alveoli with thicker walls, less developed distal airways and more inflammation than normoxia. In conclusion, we show that the rabbit model develops pulmonary hypertension and developmental lung arrest after preterm lung injury, which parallel the early changes in human BPD. Thus it enables the testing of pharmaceutical agents that target the cardiovascular compartment of the lung for further translation towards the clinic. PMID:27783043

Upregulation of autophagy decreases chlorine-induced mitochondrial injury and lung inflammation.

PubMed

Jurkuvenaite, Asta; Benavides, Gloria A; Komarova, Svetlana; Doran, Stephen F; Johnson, Michelle; Aggarwal, Saurabh; Zhang, Jianhua; Darley-Usmar, Victor M; Matalon, Sadis

2015-08-01

The mechanisms of toxicity during exposure of the airways to chlorinated biomolecules generated during the course of inflammation and to chlorine (Cl2) gas are poorly understood. We hypothesized that lung epithelial cell mitochondria are damaged by Cl2 exposure and activation of autophagy mitigates this injury. To address this, NCI-H441 (human lung adenocarcinoma epithelial) cells were exposed to Cl2 (100 ppm/15 min) and bioenergetics were assessed. One hour after Cl2, cellular bioenergetic function and mitochondrial membrane potential were decreased. These changes were associated with increased MitoSOX signal, and treatment with the mitochondrial redox modulator MitoQ attenuated these bioenergetic defects. At 6h postexposure, there was significant increase in autophagy, which was associated with an improvement of mitochondrial function. Pretreatment of H441 cells with trehalose (an autophagy activator) improved bioenergetic function, whereas 3-methyladenine (an autophagy inhibitor) resulted in increased bioenergetic dysfunction 1h after Cl2 exposure. These data indicate that Cl2 induces bioenergetic dysfunction, and autophagy plays a protective role in vitro. Addition of trehalose (2 vol%) to the drinking water of C57BL/6 mice for 6 weeks, but not 1 week, before Cl2 (400 ppm/30 min) decreased white blood cells in the bronchoalveolar lavage fluid at 6h after Cl2 by 70%. Acute administration of trehalose delivered through inhalation 24 and 1h before the exposure decreased alveolar permeability but not cell infiltration. These data indicate that Cl2 induces bioenergetic dysfunction associated with lung inflammation and suggests that autophagy plays a protective role. Published by Elsevier Inc.

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.

Effects of cyclooxygenase inhibitors on the alterations in lung mechanics caused by endotoxemia in the unanesthetized sheep.

PubMed

Snapper, J R; Hutchison, A A; Ogletree, M L; Brigham, K L

1983-07-01

The effects of Escherichia coli endotoxin on lung mechanics, hemodynamics, gas exchange, and lung fluid and solute exchange were studied in 12 chronically instrumented unanesthetized sheep. A possible role for cyclooxygenase products of arachidonate metabolism as mediators of the endotoxin-induced alterations in lung mechanics was investigated by studying sheep before and after cyclooxygenase inhibition with sodium meclofenamate and ibuprofen. Sheep were studied three times in random order: (a) sodium meclofenamate (or ibuprofen) infusion alone; (b) E. coli endotoxin alone; and (c) meclofenamate (or ibuprofen) and endotoxin. Meclofenamate alone had no effect on any of the variables measured. Endotoxin alone caused early marked changes in lung mechanics: resistance to airflow across the lungs (RL) increased 10-fold, dynamic lung compliance (Cdyn) decreased 80% and functional residual capacity (FRC) decreased by greater than 30%. The alveolar-to-arterial oxygen difference (delta AaPO2) increased markedly following endotoxemia. In the presence of sufficient meclofenamate to inhibit accumulation of thromboxane-B2 and 6-keto-prostaglandin F1 alpha in lung lymph, endotoxin caused no increase in RL, Cdyn decreased by less than 40%, and FRC decreased by only 6%. Meclofenamate significantly attenuated the hypoxemia and early pulmonary hypertension caused by endotoxemia but had no effect on the late increases in lung fluid and solute exchange. Ibuprofen had similar effects to those observed with meclofenamate. We conclude that both the pulmonary hypertension and changes in lung mechanics observed after endotoxemia may be mediated, at least in part, by constrictor prostaglandins or thromboxanes and that gas exchange may be improved by preventing endogenous synthesis of these mediators.

Ambient particulate matter and lung function growth in Chinese children.

PubMed

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

2012-05-01

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

Association between lung function in adults and plasma DDT and DDE levels: results from the Canadian Health Measures Survey.

PubMed

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

2015-05-01

Although DDT [1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane] has been banned in many countries since the 1970s, it may still pose a risk to human respiratory health. In agriculture, DDT exposures have been associated with asthma and chronic bronchitis. However, little is known about the effect of DDT on lung function. We used data on 1,696 participants 20-79 years of age from the Canadian Health Measures Survey (CHMS) and conducted multiple regression analysis to estimate associations between plasma p,p´-DDT/DDE and lung function. Almost all participants (> 99.0%) had detectable concentrations of plasma p,p´-DDE, but only 10.0% had detectable p,p´-DDT. Participants with detectable p,p´-DDT had significantly lower mean FVC (difference = 311 mL; 95% CI: -492, -130; p = 0.003) and FEV1 (difference = 232 mL; 95% CI: -408, -55; p = 0.015) than those without. A 100-ng/g lipid increase in plasma p,p´-DDE was associated with an 18.8-mL decrease in mean FVC (95% CI: -29, -9) and an 11.8-mL decrease in mean FEV1 (95% CI: -21, -3). Neither exposure was associated with FEV1/FVC ratio or FEF25%-75%. DDT exposures, which may have occurred decades ago, were still detectable among Canadians. Plasma DDT and DDE were negatively associated with lung function parameters. Additional research on the potential effects of DDT use on lung function is warranted.

Evidence for decreased lipofibroblast expression in hypoplastic rat lungs with congenital diaphragmatic hernia.

PubMed

Friedmacher, Florian; Fujiwara, Naho; Hofmann, Alejandro Daniel; Takahashi, Hiromizu; Gosemann, Jan-Hendrik; Puri, Prem

2014-10-01

Pulmonary hypoplasia (PH) is a serious condition in newborns with congenital diaphragmatic hernia (CDH). Lipid-containing interstitial fibroblasts (LIFs) play an essential role in fetal lung maturation by stimulating alveolarization and lipid homeostasis. In rodents, LIFs are first evident during the canalicular phase of lung development with a significant increase over the last 4 days of gestation. Adipocyte differentiation-related protein (ADRP), a functional lipogenic molecular marker characterizing LIFs, is highly expressed in fetal lungs during this critical time period. We hypothesized that LIF expression in hypoplastic rat lungs is decreased in the nitrofen-induced CDH model, which is accompanied by reduced alveolar ADRP expression and lipid content. On embryonic day 9.5 (E9.5), time-mated rats received either nitrofen or vehicle. Fetuses were sacrificed on selected time points E18.5 and E21.5, and dissected lungs were divided into controls and CDH-associated PH. Pulmonary gene expression levels of ADRP were determined by quantitative real-time polymerase chain reaction. ADRP immunohistochemistry and oil red O staining were used to assess pulmonary protein expression and lipid content. Immunofluorescence double staining for alpha smooth muscle actin, which is known to be absent in LIFs, and lipid droplets was performed to evaluate the pulmonary expression of this specific subset of fibroblasts. Relative mRNA expression of ADRP was significantly reduced in lungs of CDH-associated PH on E18.5 and E21.5 compared to controls. ADRP immunoreactivity and lipid staining were markedly diminished in alveolar mesenchymal cells of CDH-associated PH on E18.5 and E21.5 compared to controls. Confocal laser scanning microscopy demonstrated markedly decreased LIF expression in alveolar interstitium of CDH-associated PH on E18.5 and E21.5 compared to controls. Decreased pulmonary LIF expression during late gestation suggests impaired LIF functioning in the nitrofen-induced CDH model, which may cause disruption in fetal alveolarization and lipid homeostasis, and thus contribute to the development of PH.

Respiratory pathogens mediate the association between lung function and temperature in cystic fibrosis.

PubMed

Collaco, Joseph M; Raraigh, Karen S; Appel, Lawrence J; Cutting, Garry R

2016-11-01

Mean annual ambient temperature is a replicated environmental modifier of cystic fibrosis (CF) lung disease with warmer temperatures being associated with lower lung function. The mechanism of this relationship is not completely understood. However, Pseudomonas aeruginosa, a pathogen that infects the lungs of CF individuals and decreases lung function, also has a higher prevalence in individuals living in warmer climates. We therefore investigated the extent to which respiratory pathogens mediated the association between temperature and lung function. Thirteen respiratory pathogens observed on CF respiratory cultures were assessed in multistep fashion using clustered linear and logistic regression to determine if any mediated the association between temperature and lung function. Analysis was performed in the CF Twin-Sibling Study (n=1730; primary population); key findings were then evaluated in the U.S. CF Foundation Data Registry (n=15,174; replication population). In the primary population, three respiratory pathogens (P. aeruginosa, mucoid P. aeruginosa, and methicillin-resistant Staphylococcus aureus) mediated the association between temperature and lung function. P. aeruginosa accounted for 19% of the association (p=0.003), mucoid P. aeruginosa for 31% (p=0.001), and MRSA for 13% (p=0.023). The same three pathogens mediated association in the replication population (7%, p<0.001; 7%, p=0.002; and 4%, (p=0.002), respectively). Three important respiratory pathogens in CF mediate the association between lower lung function and warmer temperatures. These findings have implications for understanding regional variations in clinical outcomes, and interpreting results of epidemiologic studies and clinical trials that encompass regions with different ambient temperatures. Copyright © 2016 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Expression of RXFP1 Is Decreased in Idiopathic Pulmonary Fibrosis. Implications for Relaxin-based Therapies

PubMed Central

Tan, Jiangning; Tedrow, John R.; Dutta, Justin A.; Juan-Guardela, Brenda; Nouraie, Mehdi; Chu, Yanxia; Trejo Bittar, Humberto; Ramani, Kritika; Biswas, Partha S.; Veraldi, Kristen L.; Kaminski, Naftali; Zhang, Yingze

2016-01-01

Rationale: Relaxin is a hormone that has been considered as a potential therapy for patients with fibrotic diseases. Objectives: To gauge the potential efficacy of relaxin-based therapies in idiopathic pulmonary fibrosis (IPF), we studied gene expression for relaxin/insulin-like family peptide receptor 1 (RXFP1) in IPF lungs and controls. Methods: We analyzed gene expression data obtained from the Lung Tissue Research Consortium and correlated RXFP1 gene expression data with cross-sectional clinical and demographic data. We also employed ex vivo donor and IPF lung fibroblasts to test RXFP1 expression in vitro. We tested CGEN25009, a relaxin-like peptide, in lung fibroblasts and in bleomycin injury. Measurements and Main Results: We found that RXFP1 is significantly decreased in IPF. In patients with IPF, the magnitude of RXFP1 gene expression correlated directly with diffusing capacity of the lung for carbon monoxide (P < 0.0001). Significantly less RXFP1 was detected in vitro in IPF fibroblasts than in donor controls. Transforming growth factor-β decreased RXFP1 in both donor and IPF lung fibroblasts. CGEN25009 was effective at decreasing bleomycin-induced, acid-soluble collagen deposition in vivo. The relaxin-like actions of CGEN25009 were abrogated by RXFP1 silencing in vitro, and, in comparison with donor lung fibroblasts, IPF lung fibroblasts exhibited decreased sensitivity to the relaxin-like effects of CGEN25009. Conclusions: IPF is characterized by the loss of RXFP1 expression. RXFP1 expression is directly associated with pulmonary function in patients with IPF. The relaxin-like effects of CGEN25009 in vitro are dependent on expression of RXFP1. Our data suggest that patients with IPF with the highest RXFP1 expression would be predicted to be most sensitive to relaxin-based therapies. PMID:27310652

Expression of RXFP1 Is Decreased in Idiopathic Pulmonary Fibrosis. Implications for Relaxin-based Therapies.

PubMed

Tan, Jiangning; Tedrow, John R; Dutta, Justin A; Juan-Guardela, Brenda; Nouraie, Mehdi; Chu, Yanxia; Trejo Bittar, Humberto; Ramani, Kritika; Biswas, Partha S; Veraldi, Kristen L; Kaminski, Naftali; Zhang, Yingze; Kass, Daniel J

2016-12-01

Relaxin is a hormone that has been considered as a potential therapy for patients with fibrotic diseases. To gauge the potential efficacy of relaxin-based therapies in idiopathic pulmonary fibrosis (IPF), we studied gene expression for relaxin/insulin-like family peptide receptor 1 (RXFP1) in IPF lungs and controls. We analyzed gene expression data obtained from the Lung Tissue Research Consortium and correlated RXFP1 gene expression data with cross-sectional clinical and demographic data. We also employed ex vivo donor and IPF lung fibroblasts to test RXFP1 expression in vitro. We tested CGEN25009, a relaxin-like peptide, in lung fibroblasts and in bleomycin injury. We found that RXFP1 is significantly decreased in IPF. In patients with IPF, the magnitude of RXFP1 gene expression correlated directly with diffusing capacity of the lung for carbon monoxide (P < 0.0001). Significantly less RXFP1 was detected in vitro in IPF fibroblasts than in donor controls. Transforming growth factor-β decreased RXFP1 in both donor and IPF lung fibroblasts. CGEN25009 was effective at decreasing bleomycin-induced, acid-soluble collagen deposition in vivo. The relaxin-like actions of CGEN25009 were abrogated by RXFP1 silencing in vitro, and, in comparison with donor lung fibroblasts, IPF lung fibroblasts exhibited decreased sensitivity to the relaxin-like effects of CGEN25009. IPF is characterized by the loss of RXFP1 expression. RXFP1 expression is directly associated with pulmonary function in patients with IPF. The relaxin-like effects of CGEN25009 in vitro are dependent on expression of RXFP1. Our data suggest that patients with IPF with the highest RXFP1 expression would be predicted to be most sensitive to relaxin-based therapies.

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 find specific studies with obese people, justifying the need for future studies.

Lung pathology in response to repeated exposure to Staphylococcus aureus in congenic residual function cystic fibrosis mice does not increase in response to decreased CFTR levels or increased bacterial load.

PubMed

Davidson, Donald J; Webb, Sheila; Teague, Peter; Govan, John R W; Dorin, Julia R

2004-01-01

To establish the role of defects in murine Cftr in the susceptibility to Staphylococcus aureus lung disease using mouse models of cystic fibrosis (CF), congenic or inbred strains. We describe the histopathological analyses of CF mice repeatedly exposed by aerosolisation to a CF isolate of S. aureus, using residual function Cftr mice and compound heterozygotes generated by intercrossing these with Cftr 'null' mice, all congenic on the C57Bl6/N background. We demonstrate that mice congenic on the C57Bl/6 background develop significantly more severe lung pathology than non-CF littermates in response to repeated exposure to the most frequent early CF lung pathogen S. aureus. Furthermore, reducing the level of Cftr by half in compound heterozygote mice does not impact upon disease severity, even in response to an increased bacterial dose. These results are consistent with an airway clearance defect, or abnormal inflammatory response secondary to Cftr mutation. These studies confirm the primary role for Cftr mutation in the development of this lung phenotype. In addition, these results demonstrate that a further 50% decrease in residual wild-type Cftr mRNA levels in this model does not impact the severity of the histopathological response to S. aureus, suggesting a critical threshold level for functional CFTR. Copyright 2004 S. Karger AG, Basel

Pulmonary function in adolescents with ataxia telangiectasia.

PubMed

McGrath-Morrow, Sharon; Lefton-Greif, Maureen; Rosquist, Karen; Crawford, Thomas; Kelly, Amber; Zeitlin, Pamela; Carson, Kathryn A; Lederman, Howard M

2008-01-01

Pulmonary complications are common in adolescents with ataxia telangiectasia (A-T), however objective measurements of lung function may be difficult to obtain because of underlying bulbar weakness, tremors, and difficulty coordinating voluntary respiratory maneuvers. To increase the reliability of pulmonary testing, minor adjustments were made to stabilize the head and to minimize leaks in the system. Fifteen A-T adolescents completed lung volume measurements by helium dilution. To assess for reproducibility of spirometry testing, 10 A-T adolescents performed spirometry on three separate occasions. Total lung capacity (TLC) was normal or just mildly decreased in 12/15 adolescents tested. TLC correlated positively with functional residual capacity (FRC), a measurement independent of patient effort (R2=0.71). The majority of individuals had residual volumes (RV) greater than 120% predicted (10/15) and slow vital capacities (VC) less than 70% predicted (9/15). By spirometry, force vital capacity (FVC) and forced expiratory volume in 1 sec (FEV1) values were reproducible in the 10 individuals who underwent testing on three separate occasions (R=0.97 and 0.96 respectively). Seven of the 10 adolescents had FEV1/FVC ratios>90%. Lung volume measurements from A-T adolescents revealed near normal TLC values with increased RV and decreased VC values. These findings indicate a decreased ability to expire to residual volume rather then a restrictive defect. Spirometry was also found to be reproducible in A-T adolescents suggesting that spirometry testing may be useful for tracking changes in pulmonary function over time in this population. Copyright (c) 2007 Wiley-Liss, Inc.

Elevated pretransplantation soluble CD30 is associated with decreased early allograft function after human lung transplantation.

PubMed

Shah, Ashish S; Leffell, M Sue; Lucas, Donna; Zachary, Andrea A

2009-02-01

Early allograft function after lung transplantation is variable. Clinical criteria have limited predictive value for early graft function. Recipient immunologic state before LTx may affect early lung function. We investigated the association between pretransplantation soluble CD30 (sCD30), a marker of Th2-type T-cell activation, and early clinical parameters of allograft function. Between September 2002 and January 2007, a total of 80 transplantations were performed at Johns Hopkins Hospital. Of the patients, 43 had a pretransplantation sCD30 level determined. Pre- and postoperative patient variables were collected, and patients were stratified into two groups: sCD30 <20 (low sCD30) and >20 (high sCD30). High sCD30 (n = 26) and low sCD30 (n = 17) groups were similar in age, gender, and ischemia time. In the high sCD30 group, a higher percentage of patients had pulmonary fibrosis and a lower percentage had emphysema. Oxygenation at 48 hours was significantly worse in the high sCD30 group as compared with the low sCD30 (p = 0.003). Moreover, prolonged intubation and 90-day mortality were greater in the high sCD30 group. This represents the first report of the use of sCD30 as a marker for early allograft function in human lung transplanation. Increased pretransplantation recipient sCD30 appears to be associated with decreased early post-transplantation gas exchange, prolonged intubation, and early mortality.

Intravenous superoxide dismutase as a protective agent to prevent impairment of lung function induced by high tidal volume ventilation.

PubMed

Wu, Nan-Chun; Liao, Fan-Ting; Cheng, Hao-Min; Sung, Shih-Hsien; Yang, Yu-Chun; Wang, Jiun-Jr

2017-07-26

Positive-pressure mechanical ventilation is essential in assisting patients with respiratory failure in the intensive care unit and facilitating oxygenation in the operating room. However, it was also recognized as a primary factor leading to hospital-acquired pulmonary dysfunction, in which pulmonary oxidative stress and lung inflammation had been known to play important roles. Cu/Zn superoxide dismutase (SOD) is an important antioxidant, and possesses anti-inflammatory capacity. In this study, we aimed to study the efficacy of Cu/Zn SOD, administered intravenously during high tidal volume (HTV) ventilation, to prevent impairment of lung function. Thirty-eight male Sprague-Dawley rats were divided into 3 groups: 5 h ventilation with (A) low tidal volume (LTV; 8 mL/kg; n = 10), (B) high tidal volume (HTV; 18 mL/kg; n = 14), or (C) HTV and intravenous treatment of Cu/Zn SOD at a dose of 1000 U/kg/h (HTV + SOD; n = 14). Lung function was evaluated both at baseline and after 5-h ventilation. Lung injury was assessed by histological examination, lung water and protein contents in the bronchoalveolar lavage fluid (BALF). Pulmonary oxidative stress was examined by concentrations of methylguanidine (MG) and malondialdehyde (MDA) in BALF, and antioxidative activity by protein expression of glutathione peroxidase-1 (GPx-1) in the lung. Severity of lung inflammation was evaluated by white blood cell and differential count in BALF, and protein expression of inducible nitric oxide synthase (iNOS), intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factor-α (TNF-α), matrix metalloproteinase-9 (MMP-9), and mRNA expression of nuclear factor-κB (NF-κB) in the lung. We also examined protein expression of surfactant protein (SP)-A and D and we measured hourly changes in serum nitric oxide (NO) level. Five hours of LTV ventilation did not induce a major change in lung function, whereas 5 h of HTV ventilation induced apparent combined restrictive and obstructive lung disorder, together with increased pulmonary oxidative stress, decreased anti-oxidative activity and increased lung inflammation (P < 0.05). HTV ventilation also decreased SP-A and SP-D expression and suppressed serum NO level during the time course of ventilation. Cu/Zn SOD administered intravenously during HTV ventilation effectively reversed associated pulmonary oxidative stress and lung inflammation (P < 0.05); moreover, it preserved SP-A and SP-D expressions in the lung and increased serum nitric oxide (NO) level, enhancing vascular NO bioavailability. HTV ventilation can induce combined restrictive and obstructive lung disorders. Intravenous administration of Cu/Zn SOD during HTV ventilation can prevent lung function impairment and lung injury via reducing pulmonary oxidative stress and lung inflammation, preserving pulmonary surfactant expression, and enhancing vascular NO bioavailability.

Association between Lung Function in Adults and Plasma DDT and DDE Levels: Results from the Canadian Health Measures Survey

PubMed Central

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

2014-01-01

Background Although DDT [1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane] has been banned in many countries since the 1970s, it may still pose a risk to human respiratory health. In agriculture, DDT exposures have been associated with asthma and chronic bronchitis. However, little is known about the effect of DDT on lung function. Methods We used data on 1,696 participants 20–79 years of age from the Canadian Health Measures Survey (CHMS) and conducted multiple regression analysis to estimate associations between plasma p,p´-DDT/DDE and lung function. Results Almost all participants (> 99.0%) had detectable concentrations of plasma p,p´-DDE, but only 10.0% had detectable p,p´-DDT. Participants with detectable p,p´-DDT had significantly lower mean FVC (difference = 311 mL; 95% CI: –492, –130; p = 0.003) and FEV1 (difference = 232 mL; 95% CI: –408, –55; p = 0.015) than those without. A 100-ng/g lipid increase in plasma p,p´-DDE was associated with an 18.8-mL decrease in mean FVC (95% CI: –29, –9) and an 11.8-mL decrease in mean FEV1 (95% CI: –21, –3). Neither exposure was associated with FEV1/FVC ratio or FEF25%–75%. Conclusions DDT exposures, which may have occurred decades ago, were still detectable among Canadians. Plasma DDT and DDE were negatively associated with lung function parameters. Additional research on the potential effects of DDT use on lung function is warranted. Citation Ye M, Beach J, Martin JW, Senthilselvan A. 2015. Association between lung function in adults and plasma DDT and DDE levels: results from the Canadian Health Measures Survey. Environ Health Perspect 123:422–427; http://dx.doi.org/10.1289/ehp.1408217 PMID:25536373

SU-C-BRA-06: Developing Clinical and Quantitative Guidelines for a 4DCT-Ventilation Functional Avoidance Clinical Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vinogradskiy, Y; Waxweiler, T; Diot, Q

Purpose: 4DCT-ventilation is an exciting new imaging modality that uses 4DCTs to calculate lung ventilation. Because 4DCTs are acquired as part of routine care, calculating 4DCT-ventilation allows for lung function evaluation without additional cost or inconvenience to the patient. Development of a clinical trial is underway at our institution to use 4DCT-ventilation for thoracic functional avoidance with the idea that preferential sparing of functional lung regions can decrease pulmonary toxicity. The purpose of our work was to develop the practical aspects of a 4DCT-ventilation functional avoidance clinical trial including: 1.assessing patient eligibility 2.developing trial inclusion criteria and 3.developing treatment planningmore » and dose-function evaluation strategies. Methods: 96 stage III lung cancer patients from 2 institutions were retrospectively reviewed. 4DCT-ventilation maps were calculated using the patient’s 4DCTs, deformable image registrations, and a density-change-based algorithm. To assess patient eligibility and develop trial inclusion criteria we used an observer-based binary end point noting the presence or absence of a ventilation defect and developed an algorithm based on the percent ventilation in each lung third. Functional avoidance planning integrating 4DCT-ventilation was performed using rapid-arc and compared to the patient’s clinically used plan. Results: Investigator-determined clinical ventilation defects were present in 69% of patients. Our regional/lung-thirds ventilation algorithm identified that 59% of patients have lung functional profiles suitable for functional avoidance. Compared to the clinical plan, functional avoidance planning was able to reduce the mean dose to functional lung by 2 Gy while delivering comparable target coverage and cord/heart doses. Conclusions: 4DCT-ventilation functional avoidance clinical trials have great potential to reduce toxicity, and our data suggest that 59% of lung cancer patients have lung function profiles suitable for functional avoidance. Our study used a retrospective evaluation of a large lung cancer patient database to develop the practical aspects of a 4DCT-ventilation functional avoidance clinical trial. (R.C., E.C., T.G.), NIH Research Scientist Development Award K01-CA181292 (R.C.), and State of Colorado Advanced Industries Accelerator Grant (Y.V.)« less

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.

Long non-coding RNA OIP5-AS1 promotes proliferation of lung cancer cells and leads to poor prognosis by targeting miR-378a-3p.

PubMed

Wang, Maolong; Sun, Xiao; Yang, Yuling; Jiao, Wenjie

2018-06-13

The antisense of the OIP5-AS1 gene is a long non-coding RNA (lncRNA) that is reported to be upregulated and promotes cell proliferation in multiple human cancers; however, its function in lung cancer is unknown. We investigated the regulatory function and underlying mechanisms of OIP5-AS1 in lung cancer. OIP5-AS1 and microRNA (miR)-378a-3p expression were assayed by quantitative real-time PCR, and proliferation-related protein expression was measured by Western blotting. Cell viability was detected using methyl thiazolyl tetrazolium assay. Luciferase reporter assay and RNA immunoprecipitation were used to detect the direct regulation of miR-378a-3p by OIP5-AS1. Nude mice were used to test the function of OIP5-AS1 in vivo. OIP5-AS1 was highly expressed in lung cancer tissues and was correlated with tumor size and tumor growth speed. OIP5-AS1 overexpression increased lung cancer cell proliferation in vitro. Further investigation revealed that OIP5-AS1 functions as a competing endogenous RNA of miR-378a-3p. MiR-378a-3p overexpression inhibited cell proliferation and caused proliferation-associated proteins CDK4 and CDK6 to decrease in A549 cells. Overexpression of wild type OIP5-AS1 led to strong CDK4 and CDK6 expression; however, these two proteins did not change when mutated OIP5-AS1 was upregulated. Finally, in vivo assay showed that the speed of tumor growth was increased and decreased when OIP5-AS1 was upregulated and downregulated, respectively. Our results revealed that OIP5-AS1 acts as a growth-promoting lncRNA in lung cancer by suppressing miR-378a-3p function. OIP5-AS1 and miR-378a-3p interaction may provide a potential target for lung cancer treatment. © 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

Idiopathic pulmonary fibrosis: current understanding of the pathogenesis and the status of treatment.

PubMed

Khalil, Nasreen; O'Connor, Robert

2004-07-20

Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal pulmonary fibrotic lung disease. The diagnostic histological changes are called usual interstitial pneumonia and are characterized by histological temporal heterogeneity, whereby normal lung tissue is interspersed with interstitial fibrosis, honeycomb cysts and fibroblast foci. Pulmonary functions show restricted volumes and capacities, preserved flows and evidence of decreased gas exchange. High-resolution computed axial tomography demonstrates evidence of fibrosis and lung remodelling such as honeycomb cysts and traction bronchiectasis. There is no known effective treatment for IPF, but lung transplantation improves survival.

[USE OF PROTECTIVE LUNG VENTILATION REGIMEN IN CARDIAC SURGERY PATIENTS.

PubMed

Pshenichniy, T A; Akselrod, B A; Titova, I V; Trekova, N A; Khrustaleva, M V

2017-09-01

In cardiac surgery, protective lung ventilation and/or preventive brdnchoscopy (PB) are able to decrease lung injury effects of cardiopulmonary bypass (CPB) and mechanical ventilation. define lung complication risks, evaluate the effect ofprotective lung ventilation (PLV) on lung functioning, and investigate the feasibility ofpreventive PB in higher pulmonary risk (PR) patients. 66 patients participated in prospective randomized research. Allocation was based on PR and intraoperative mechanical ventilation type. PLV includedfollowing parameters: PCK PIP - up to 20 cm H20, Vt - 6 ml/ kg of PBW, PEEP - 5-10 cm H20, IE ratio - 1:1.5-1:1, EtCO2 - 35-42 mm Hg, FiO2 - 45-60%, lung ventilation during CPB, alveolar recruitment. Four groups were formed: A - higher PR plus PLV- B - higher PR plus conventional LV (CLV), C - lower PR plus PLV- D - lower PR plus CLV PIP PEEP dynamic compliance, p/f ratio and intrapulmonary shunt (Qs/Qt) were recorded. Seventeen patients of group A underwent PB. Advanced dynamic compliance, higher p/f ratio and lower Qs/Qt were seen in group A, in comparison with group B (p< 0.05). Lower Qs/Qt was seen in group C, in comparison with group D (p<0.05). Mucus obstruction of subsegmental bronchi was observed in 53.3% of higher PR patients. More than half ofpatients without PB sufferedfrom postoperative lung complications (70.4 vs. 34.2 7%, p

miR‐34b‐5p inhibition attenuates lung inflammation and apoptosis in an LPS‐induced acute lung injury mouse model by targeting progranulin

PubMed Central

Xie, Wang; Lu, Qingchun; Wang, Kailing; Lu, Jingjing; Gu, Xia; Zhu, Dongyi; Liu, Fanglei

2018-01-01

Inflammation and apoptosis play important roles in the initiation and progression of acute lung injury (ALI). Our previous study has shown that progranulin (PGRN) exerts lung protective effects during LPS‐induced ALI. Here, we have investigated the potential roles of PGRN‐targeting microRNAs (miRNAs) in regulating inflammation and apoptosis in ALI and have highlighted the important role of PGRN. LPS‐induced lung injury and the protective roles of PGRN in ALI were first confirmed. The function of miR‐34b‐5p in ALI was determined by transfection of a miR‐34b‐5p mimic or inhibitor in intro and in vivo. The PGRN level gradually increased and subsequently significantly decreased, reaching its lowest value by 24 hr; PGRN was still elevated compared to the control. The change was accompanied by a release of inflammatory mediators and accumulation of inflammatory cells in the lungs. Using bioinformatics analysis and RT‐PCR, we demonstrated that, among 12 putative miRNAs, the kinetics of the miR‐34b‐5p levels were closely associated with PGRN expression in the lung homogenates. The gain‐ and loss‐of‐function analysis, dual‐luciferase reporter assays, and rescue experiments confirmed that PGRN was the functional target of miR‐34b‐5p. Intravenous injection of miR‐34b‐5p antagomir in vivo significantly inhibited miR‐34b‐5p up‐regulation, reduced inflammatory cytokine release, decreased alveolar epithelial cell apoptosis, attenuated lung inflammation, and improved survival by targeting PGRN during ALI. miR‐34b‐5p knockdown attenuates lung inflammation and apoptosis in an LPS‐induced ALI mouse model by targeting PGRN. This study shows that miR‐34b‐5p and PGRN may be potential targets for ALI treatments. PMID:29150939

Enhanced ventricular pump function and decreased reservoir backflow sustain rise in pulmonary blood flow after reduction of lung liquid volume in fetal lambs.

PubMed

Smolich, Joseph J

2014-02-15

Although a reduction in lung liquid volume increases fetal pulmonary blood flow, the changes in central flow patterns that sustain this increased pulmonary perfusion are unknown. To address this issue, eight anesthetized late-gestation fetal sheep were instrumented with pulmonary trunk (PT), ductus arteriosus (DA), and left pulmonary artery (PA) micromanometer catheters and transit-time flow probes, with blood flow profile and wave intensity analyses performed at baseline and after withdrawal of lung liquid via an endotracheal tube. Reducing lung liquid volume by 19 ± 6 ml/kg (mean ± SD) augmented right ventricular power by 34% (P < 0.001), with distribution of an accompanying increase in mean PT blood flow (245 ± 63 ml/min, P < 0.001) to the lungs (169 ± 91 ml/min, P = 0.001) and across the DA (77 ± 92 ml/min, P = 0.04). However, although PT and DA flow increments were confined to systole and were related to an increased magnitude of flow-increasing, forward-running compression waves, the rise in PA flow spanned both systole (108 ± 66 ml/min) and diastole (61 ± 32 ml/min). Flow profile analysis showed that the step-up in PA diastolic flow was associated with diminished PA diastolic backflow and accompanied by a lesser degree of diastolic right-to-left DA shunting. These data suggest that an increased pulmonary blood flow after reduction of lung liquid volume is associated with substantial changes in PT-DA-PA interactions and underpinned by two main factors: 1) enhanced right ventricular pump function that increases PA systolic inflow and 2) decreased PA diastolic backflow that arises from a fundamental change in PA reservoir function, thereby resulting in greater passage of systolic inflow through the lungs.

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

Changes in lung volumes and gas trapping in patients with large hiatal hernia.

PubMed

Naoum, Christopher; Kritharides, Leonard; Ing, Alvin; Falk, Gregory L; Yiannikas, John

2017-03-01

Studies assessing hiatal hernia (HH)-related effects on lung volumes derived by body plethysmography are limited. We aimed to evaluate the effect of hernia size on lung volumes (including assessment by body plethysmography) and the relationship to functional capacity, as well as the impact of corrective surgery. Seventy-three patients (70 ± 10 years; 54 female) with large HH [mean ± standard deviation, intra-thoracic stomach (ITS) (%): 63 ± 20%; type III in 65/73] had respiratory function data (spirometry, 73/73; body plethysmography, 64/73; diffusing capacity, 71/73) and underwent HH surgery. Respiratory function was analysed in relation to hernia size (groups I, II and III: ≤50, 50%-75% and ≥75% ITS, respectively) and functional capacity. Post-operative changes were quantified in a subgroup. Total lung capacity (TLC) and vital capacity (VC) correlated inversely with hernia size (TLC: 97 ± 11%, 96 ± 13%, 88 ± 10% predicted in groups I, II and III, respectively, P = 0.01; VC: 110 ± 17%, 111 ± 14%, 98 ± 14% predicted, P = 0.02); however, mean values were normal and only 14% had abnormal lung volumes. Surgery increased TLC (93 ± 11% vs 97 ± 10% predicted) and VC (105 ± 15% vs 116 ± 18%), and decreased residual volume/total lung capacity (RV/TLC) ratio (39 ± 7% vs 37 ± 6%) (P < 0.01 for all). Respiratory changes were modest relative to the marked functional class improvement. Among parameters that improved following HH surgery, decreased TLC and forced expiratory volume in 1 s and increased RV/TLC ratio correlated with poorer functional class pre-operatively. Increasing HH size correlates with reduced TLC and VC. Surgery improves lung volumes and gas trapping; however, the changes are mild and within the normal range. © 2015 John Wiley & Sons Ltd.

Multiple image x-radiography for functional lung imaging

NASA Astrophysics Data System (ADS)

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

2018-01-01

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

Assessment of volume reduction effect after lung lobectomy for cancer.

PubMed

Ueda, Kazuhiro; Murakami, Junichi; Sano, Fumiho; Hayashi, Masataro; Kobayashi, Taiga; Kunihiro, Yoshie; Hamano, Kimikazu

2015-07-01

Lung lobectomy results in an unexpected improvement of the remaining lung function in some patients with moderate-to-severe emphysema. Because the lung function is the main limiting factor for therapeutic decision making in patients with lung cancer, it may be advantageous to identify patients who may benefit from the volume reduction effect, particularly those with a poor functional reserve. We measured the regional distribution of the emphysematous lung and normal lung using quantitative computed tomography in 84 patients undergoing lung lobectomy for cancer between January 2010 and December 2012. The volume reduction effect was diagnosed using a combination of radiologic and spirometric parameters. Eight patients (10%) were favorably affected by the volume reduction effect. The forced expiratory volume in one second increased postoperatively in these eight patients, whereas the forced vital capacity was unchanged, thus resulting in an improvement of the airflow obstruction postoperatively. This improvement was not due to a compensatory expansion of the remaining lung but was associated with a relative decrease in the forced end-expiratory lung volume. According to a multivariate analysis, airflow obstruction and the forced end-expiratory lung volume were independent predictors of the volume reduction effect. A combined assessment using spirometry and quantitative computed tomography helped to characterize the respiratory dynamics underlying the volume reduction effect, thus leading to the identification of novel predictors of a volume reduction effect after lobectomy for cancer. Verification of our results by a large-scale prospective study may help to extend the indications for lobectomy in patients with oncologically resectable lung cancer who have a marginal pulmonary function. Copyright © 2015 Elsevier Inc. All rights reserved.

[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. Copyright © 2015 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

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

Galectin-3 Is Associated with Restrictive Lung Disease and Interstitial Lung Abnormalities.

PubMed

Ho, Jennifer E; Gao, Wei; Levy, Daniel; Santhanakrishnan, Rajalakshmi; Araki, Tetsuro; Rosas, Ivan O; Hatabu, Hiroto; Latourelle, Jeanne C; Nishino, Mizuki; Dupuis, Josée; Washko, George R; O'Connor, George T; Hunninghake, Gary M

2016-07-01

Galectin-3 (Gal-3) has been implicated in the development of pulmonary fibrosis in experimental studies, and Gal-3 levels have been found to be elevated in small studies of human pulmonary fibrosis. We sought to study whether circulating Gal-3 concentrations are elevated early in the course of pulmonary fibrosis. We examined 2,596 Framingham Heart Study participants (mean age, 57 yr; 54% women; 14% current smokers) who underwent Gal-3 assessment using plasma samples and pulmonary function testing between 1995 and 1998. Of this sample, 1,148 underwent subsequent volumetric chest computed tomography. Higher Gal-3 concentrations were associated with lower lung volumes (1.4% decrease in percentage of predicted FEV1 per 1 SD increase in log Gal-3; 95% confidence interval [CI], 0.8-2.0%; P < 0.001; 1.2% decrease in percentage of predicted FVC; 95% CI, 0.6-1.8%; P < 0.001) and decreased diffusing capacity of the lung for carbon monoxide (2.1% decrease; 95% CI, 1.3-2.9%; P < 0.001). These associations remained significant after multivariable adjustment (P ≤ 0.008 for all). Compared with the lowest quartile, participants in the highest Gal-3 quartile were more than twice as likely to have interstitial lung abnormalities visualized by computed tomography (multivariable-adjusted odds ratio, 2.67; 95% CI, 1.49-4.76; P < 0.001). Elevated Gal-3 concentrations are associated with interstitial lung abnormalities coupled with a restrictive pattern, including decreased lung volumes and altered gas exchange. These findings suggest a potential role for Gal-3 in early stages of pulmonary fibrosis.

Galectin-3 Is Associated with Restrictive Lung Disease and Interstitial Lung Abnormalities

PubMed Central

Gao, Wei; Levy, Daniel; Santhanakrishnan, Rajalakshmi; Araki, Tetsuro; Rosas, Ivan O.; Hatabu, Hiroto; Latourelle, Jeanne C.; Nishino, Mizuki; Dupuis, Josée; Washko, George R.; O’Connor, George T.; Hunninghake, Gary M.

2016-01-01

Rationale: Galectin-3 (Gal-3) has been implicated in the development of pulmonary fibrosis in experimental studies, and Gal-3 levels have been found to be elevated in small studies of human pulmonary fibrosis. Objectives: We sought to study whether circulating Gal-3 concentrations are elevated early in the course of pulmonary fibrosis. Methods: We examined 2,596 Framingham Heart Study participants (mean age, 57 yr; 54% women; 14% current smokers) who underwent Gal-3 assessment using plasma samples and pulmonary function testing between 1995 and 1998. Of this sample, 1,148 underwent subsequent volumetric chest computed tomography. Measurements and Main Results: Higher Gal-3 concentrations were associated with lower lung volumes (1.4% decrease in percentage of predicted FEV1 per 1 SD increase in log Gal-3; 95% confidence interval [CI], 0.8–2.0%; P < 0.001; 1.2% decrease in percentage of predicted FVC; 95% CI, 0.6–1.8%; P < 0.001) and decreased diffusing capacity of the lung for carbon monoxide (2.1% decrease; 95% CI, 1.3–2.9%; P < 0.001). These associations remained significant after multivariable adjustment (P ≤ 0.008 for all). Compared with the lowest quartile, participants in the highest Gal-3 quartile were more than twice as likely to have interstitial lung abnormalities visualized by computed tomography (multivariable-adjusted odds ratio, 2.67; 95% CI, 1.49–4.76; P < 0.001). Conclusions: Elevated Gal-3 concentrations are associated with interstitial lung abnormalities coupled with a restrictive pattern, including decreased lung volumes and altered gas exchange. These findings suggest a potential role for Gal-3 in early stages of pulmonary fibrosis. PMID:26771117

Ozone Exposure, Cardiopulmonary Health, and Obesity: A Substantive Review.

PubMed

Koman, Patricia D; Mancuso, Peter

2017-07-17

From 1999-2014, obesity prevalence increased among adults and youth. Obese individuals may be uniquely susceptible to the proinflammatory effects of ozone because obese humans and animals have been shown to experience a greater decline in lung function than normal-weight subjects. Obesity is independently associated with limitations in lung mechanics with increased ozone dose. However, few epidemiologic studies have examined the interaction between excess weight and ozone exposure among adults. Using PubMed keyword searches and reference lists, we reviewed epidemiologic evidence to identify potential response-modifying factors and determine if obese or overweight adults are at increased risk of ozone-related health effects. We initially identified 170 studies, of which seven studies met the criteria of examining the interaction of excess weight and ozone exposure on cardiopulmonary outcomes in adults, including four short-term ozone exposure studies in controlled laboratory settings and three community epidemiologic studies. In the studies identified, obesity was associated with decreased lung function and increased inflammatory mediators. Results were inconclusive about the effect modification when data were stratified by sex. Obese and overweight populations should be considered as candidate at-risk groups for epidemiologic studies of cardiopulmonary health related to air pollution exposures. Air pollution is a modifiable risk factor that may decrease lung function among obese individuals with implications for environmental and occupational health policy.

Thioredoxin-deficient mice, a novel phenotype sensitive to ambient air and hypersensitive to hyperoxia-induced lung injury

PubMed Central

2014-01-01

Pulmonary oxygen toxicity is a major clinical problem for patients undergoing supplemental oxygen therapy. Thioredoxin (Trx) is an endogenous antioxidant protein that regenerates oxidatively inactivated proteins. We examined how Trx contributes to oxygen tolerance by creating transgenic mice with decreased levels of functional thioredoxin (dnTrx-Tg) using a dominant-negative approach. These mice showed decreased Trx activity in the lung although the expression of mutant protein is three times higher than the wild-type mice. Additionally, we found that these mice showed increased oxidation of endogenous Trx in room air. When exposed to hyperoxia (>90% O2) for 4 days, they failed to recover and showed significant mortality. Even in normal oxygen levels, these mice displayed a significant decrease in aconitase and NADH dehydrogenase activities, decreased mitochondrial energy metabolism, increased p53 and Gadd45α expression, and increased synthesis of proinflammatory cytokines. These effects were further increased by hyperoxia. We also generated mice overexpressing Trx (Trx-Tg) and found they maintained lung redox balance during exposure to high oxygen and thus were resistant to hyperoxia-induced lung injury. These mice had increased levels of reduced Trx in the lung in normoxia as well as hyperoxia. Furthermore, the levels of aconitase and NADH dehydrogenase activities were maintained in these mice concomitant with maintenance of mitochondrial energy metabolism. The genotoxic stress markers such as p53 or Gadd45α remained in significantly lower levels in hyperoxia compared with dnTrx-Tg or wild-type mice. These studies establish that mice deficient in functional Trx exhibit a phenotype of sensitivity to ambient air and hypersensitivity to hyperoxia. PMID:25539854

Long-term ambient air pollution and lung function impairment in Chinese children from a high air pollution range area: The Seven Northeastern Cities (SNEC) study

NASA Astrophysics Data System (ADS)

Zeng, Xiao-Wen; Vivian, Elaina; Mohammed, Kahee A.; Jakhar, Shailja; Vaughn, Michael; Huang, Jin; Zelicoff, Alan; Xaverius, Pamela; Bai, Zhipeng; Lin, Shao; Hao, Yuan-Tao; Paul, Gunther; Morawska, Lidia; Wang, Si-Quan; Qian, Zhengmin; Dong, Guang-Hui

2016-08-01

Epidemiological studies have reported inconsistent and inconclusive associations between long-term exposure to ambient air pollution and lung function in children from Europe and America, where air pollution levels were typically low. The aim of the present study is to examine the relationship between air pollutants and lung function in children selected from heavily industrialized and polluted cities in northeastern China. During 2012, 6740 boys and girls aged 7-14 years were recruited in 24 districts of seven northeastern cities. Portable electronic spirometers were used to measure lung function. Four-year average concentrations of particulate matter with an aerodynamic diameter ≤10 μm (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), and ozone (O3) were measured at monitoring stations in the 24 districts. Two-staged regression models were used in the data analysis, controlling for covariates. Overall, for all subjects, the increased odds of lung function impairment associated with exposure to air pollutants, ranged from 5% (adjusted odds ratio [aOR] = 1.05; 95% confidence interval [CI] = 1.01, 1.10) for FVC < 85% predicted per 46.3 μg/m3 for O3 to 81% (aOR = 1.81; 95%CI = 1.44, 2.28) for FEV1 < 85% predicted per 30.6 μg/m3 for PM10. The linear regression models consistently showed a negative relationship between all air pollutants and lung function measures across subjects. There were significant interaction terms indicating gender differences for lung function impairment and pulmonary function from exposure to some pollutants (P < 0.10). In conclusion, long term exposure to high concentrations of ambient air pollution is associated with decreased pulmonary function and lung function impairment, and females appear to be more susceptible than males.

Lung inflation with hydrogen during the cold ischemia phase decreases lung graft injury in rats

PubMed Central

Liu, Rongfang; Fang, Xianhai; Meng, Chao; Xing, Jingchun; Liu, Jinfeng; Yang, Wanchao

2015-01-01

Hydrogen has antioxidant and anti-inflammatory effects on lung ischemia–reperfusion injury when it is inhaled by donor or/and recipient. This study examined the effects of lung inflation with 3% hydrogen during the cold ischemia phase on lung graft function in rats. The donor lung was inflated with 3% hydrogen, 40% oxygen, and 57% nitrogen at 5 mL/kg, and the gas was replaced every 20 min during the cold ischemia phase for 2 h. In the control group, the donor lung was inflated with 40% oxygen and 60% nitrogen at 5 mL/kg. The recipient was euthanized 2 h after orthotropic lung transplantation. The hydrogen concentration in the donor lung during the cold ischemia phase was 1.99–3%. The oxygenation indices in the arterial blood and pulmonary vein blood were improved in the hydrogen group. The inflammation response indices, including lung W/D ratio, the myeloperoxidase activity in the grafts, and the levels of IL-8 and TNF-α in serum, were significantly lower in the hydrogen group (5.2 ± 0.8, 0.76 ± 0.32 U/g, 340 ± 84 pg/mL, and 405 ± 115 pg/mL, respectively) than those in the control group (6.5 ± 0.7, 1.1 ± 0.5 U/g, 443 ± 94 pg/mL, and 657 ± 96 pg/mL, respectively (P < 0.05), and the oxidative stress indices, including the superoxide dismutase activity and the level of malonaldehyde in lung grafts were improved after hydrogen application. Furthermore, the lung injury score determined by histopathology, the cell apoptotic index, and the caspase-3 protein expression in lung grafts were decreased after hydrogen treatment, and the static pressure–volume curve of lung graft was improved by hydrogen inflation. In conclusion, lung inflation with 3% hydrogen during the cold ischemia phase alleviated lung graft injury and improved graft function. PMID:25662956

Atopic asthmatic subjects but not atopic subjects without ...

EPA Pesticide Factsheets

BACKGROUND: Asthma is a known risk factor for acute ozone-associated respiratory disease. Ozone causes an immediate decrease in lung function and increased airway inflammation. The role of atopy and asthma in modulation of ozone-induced inflammation has not been determined. OBJECTIVE: We sought to determine whether atopic status modulates ozone response phenotypes in human subjects. METHODS: Fifty volunteers (25 healthy volunteers, 14 atopic nonasthmatic subjects, and 11 atopic asthmatic subjects not requiring maintenance therapy) underwent a 0.4-ppm ozone exposure protocol. Ozone response was determined based on changes in lung function and induced sputum composition, including airway inflammatory cell concentration, cell-surface markers, and cytokine and hyaluronic acid concentrations. RESULTS: All cohorts experienced similar decreases in lung function after ozone. Atopic and atopic asthmatic subjects had increased sputum neutrophil numbers and IL-8 levels after ozone exposure; values did not significantly change in healthy volunteers. After ozone exposure, atopic asthmatic subjects had significantly increased sputum IL-6 and IL-1beta levels and airway macrophage Toll-like receptor 4, Fc(epsilon)RI, and CD23 expression; values in healthy volunteers and atopic nonasthmatic subjects showed no significant change. Atopic asthmatic subjects had significantly decreased IL-10 levels at baseline compared with healthy volunteers; IL-10 levels did not significa

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.

Intrauterine growth restriction decreases nuclear factor-kappa B signaling in fetal pulmonary artery endothelial cells of fetal sheep.

PubMed

Dodson, R Blair; Powers, Kyle N; Gien, Jason; Rozance, Paul J; Seedorf, Gregory J; Astling, David; Jones, Kenneth Lloyd; Crombleholme, Timothy M; Abman, Steven H; Alvira, Cristina M

2018-05-03

Intrauterine growth restriction (IUGR) in premature newborns increases the risk for bronchopulmonary dysplasia (BPD), a chronic lung disease characterized by disrupted pulmonary angiogenesis and alveolarization. We previously showed that experimental IUGR impairs angiogenesis, however, mechanisms that impair pulmonary artery endothelial cell (PAEC) function are uncertain. The nuclear factor-kappa-B (NFκB) pathway promotes vascular growth in the developing mouse lung, and we hypothesized that IUGR disrupts NFκB-regulated pro-angiogenic targets in fetal PAEC. PAECs were isolated from lungs of control fetal sheep and sheep with experimental IUGR from an established model of chronic placental insufficiency. Microarray analysis identified suppression of NFκB signaling and significant alterations in extracellular matrix (ECM) pathways in IUGR PAEC, including decreases in collagen 4α1 and laminin α4, components of the basement membrane and putative NFκB targets. In comparison with controls: (i) immunostaining of active NFκB complexes; (ii) NFκB-DNA binding; (iii) baseline expression of NFκB subunits, p65 and p50; and (iv) LPS-mediated inducible activation of NFκB signaling were decreased in IUGR PAEC. Although pharmacologic NFκB inhibition did not affect angiogenic function in IUGR PAEC, angiogenic function of control PAEC was reduced to a similar degree as that observed in IUGR PAEC. These data identify reductions in endothelial NFκB signaling as central to the disrupted angiogenesis observed in IUGR, likely by impairing both intrinsic PAEC angiogenic function and NFκB-mediated regulation of ECM components necessary for vascular development. These data further suggest that strategies that preserve endothelial NFκB activation may be useful in lung diseases marked by disrupted angiogenesis such as IUGR.

Interaction Effects of Temperature and Ozone on Lung Function and Markers of Systemic Inflammation, Coagulation, and Fibrinolysis: A Crossover Study of Healthy Young Volunteers

PubMed Central

Kahle, Juliette J.; Neas, Lucas M.; Devlin, Robert B.; Case, Martin W.; Schmitt, Michael T.; Madden, Michael C.

2014-01-01

Background: Trends in climate suggest that extreme weather events such as heat waves will become more common. High levels of the gaseous pollutant ozone are associated with elevated temperatures. Ozone has been associated with respiratory diseases as well as cardiovascular morbidity and mortality and can reduce lung function and alter systemic markers of fibrinolysis. The interaction between ozone and temperature is unclear. Methods: Sixteen healthy volunteers were exposed in a randomized crossover study to 0.3 ppm ozone and clean air for 2 hr at moderate (22°C) temperature and again at an elevated temperature (32.5°C). In each case lung function was performed and blood taken before and immediately after exposure and the next morning. Results: Ozone exposure at 22°C resulted in a decrease in markers of fibrinolysis the next day. There was a 51.8% net decrease in PAI-1 (plasminogen activator inhibitor-1), a 12.1% net decrease in plasminogen, and a 17.8% net increase in D-dimer. These significantly differed from the response at 32.5°C, where there was a 44.9% (p = 0.002) and a 27.9% (p = 0.001) increase in PAI-1 and plasminogen, respectively, and a 12.5% (p = 0.042) decrease in D-dimer. In contrast, decrements in lung function following ozone exposure were comparable at both moderate and elevated temperatures (forced expiratory volume in 1 sec, –12.4% vs. –7.5%, p > 0.05). No changes in systemic markers of inflammation were observed for either temperature. Conclusion: Ozone-induced systemic but not respiratory effects varied according to temperature. Our study suggests that at moderate temperature ozone may activate the fibrinolytic pathway, while at elevated temperature ozone may impair it. These findings provide a biological basis for the interaction between temperature and ozone on mortality observed in some epidemiologic studies. Citation: Kahle JJ, Neas LM, Devlin RB, Case MW, Schmitt MT, Madden MC, Diaz-Sanchez D. 2015. Interaction effects of temperature and ozone on lung function and markers of systemic inflammation, coagulation, and fibrinolysis: a crossover study of healthy young volunteers. Environ Health Perspect 123:310–316; http://dx.doi.org/10.1289/ehp.1307986 PMID:25514459

Self-reported physical activity and lung function two months after cardiac surgery--a prospective cohort study.

PubMed

Jonsson, Marcus; Urell, Charlotte; Emtner, Margareta; Westerdahl, Elisabeth

2014-03-28

Physical activity has well-established positive health-related effects. Sedentary behaviour has been associated with postoperative complications and mortality after cardiac surgery. Patients undergoing cardiac surgery often suffer from impaired lung function postoperatively. The association between physical activity and lung function in cardiac surgery patients has not previously been reported. Patients undergoing cardiac surgery were followed up two months postoperatively. Physical activity was assessed on a four-category scale (sedentary, moderate activity, moderate regular exercise, and regular activity and exercise), modified from the Swedish National Institute of Public Health's national survey. Formal lung function testing was performed preoperatively and two months postoperatively. The sample included 283 patients (82% male). Two months after surgery, the level of physical activity had increased (p < 0.001) in the whole sample. Patients who remained active or increased their level of physical activity had significantly better recovery of lung function than patients who remained sedentary or had decreased their level of activity postoperatively in terms of vital capacity (94 ± 11% of preoperative value vs. 91 ± 9%; p = 0.03), inspiratory capacity (94 ± 14% vs. 88 ± 19%; p = 0.008), and total lung capacity (96 ± 11% vs. 90 ± 11%; p = 0.01). An increased level of physical activity, compared to preoperative level, was reported as early as two months after surgery. Our data shows that there could be a significant association between physical activity and recovery of lung function after cardiac surgery. The relationship between objectively measured physical activity and postoperative pulmonary recovery needs to be further examined to verify these results.

Mesothelial- and epithelial-derived FGF9 have distinct functions in the regulation of lung development

PubMed Central

Yin, Yongjun; Wang, Fen; Ornitz, David M.

2011-01-01

Fibroblast growth factor (FGF) 9 is a secreted signaling molecule that is expressed in lung mesothelium and epithelium and is required for lung development. Embryos lacking FGF9 show mesenchymal hypoplasia, decreased epithelial branching and, by the end of gestation, hypoplastic lungs that cannot support life. Mesenchymal FGF signaling interacts with β-catenin-mediated WNT signaling in a feed-forward loop that functions to sustain mesenchymal FGF responsiveness and mesenchymal WNT/β-catenin signaling. During pseudoglandular stages of lung development, Wnt2a and Wnt7b are the canonical WNT ligands that activate mesenchymal WNT/β-catenin signaling, whereas FGF9 is the only known ligand that signals to mesenchymal FGF receptors (FGFRs). Here, we demonstrate that mesothelial- and epithelial-derived FGF9, mesenchymal Wnt2a and epithelial Wnt7b have unique functions in lung development in mouse. Mesothelial FGF9 and mesenchymal WNT2A are principally responsible for maintaining mesenchymal FGF-WNT/β-catenin signaling, whereas epithelial FGF9 primarily affects epithelial branching. We show that FGF signaling is primarily responsible for regulating mesenchymal proliferation, whereas β-catenin signaling is a required permissive factor for mesenchymal FGF signaling. PMID:21750028

Exposure to neonatal cigarette smoke causes durable lung changes but does not potentiate cigarette smoke–induced chronic obstructive pulmonary disease in adult mice

PubMed Central

McGrath-Morrow, Sharon; Malhotra, Deepti; Lauer, Thomas; Collaco, J. Michael; Mitzner, Wayne; Neptune, Enid; Wise, Robert; Biswal, Shyam

2016-01-01

The impact of early childhood cigarette smoke (CS) exposure on CS-induced chronic obstructive pulmonary disease (COPD) is unknown. This study was performed to evaluate the individual and combined effects of neonatal and adult CS exposure on lung structure, function, and gene expression in adult mice. To model a childhood CS exposure, neonatal C57/B6 mice were exposed to 14 days of CS (Neo CS). At 10 weeks of age, Neo CS and control mice were exposed to 4 months of CS. Pulmonary function tests, bronchoalveolar lavage, and lung morphometry were measured and gene expression profiling was performed on lung tissue. Mean chord lengths and lung volumes were increased in neonatal and/or adult CS-exposed mice. Differences in immune, cornified envelope protein, muscle, and erythrocyte genes were found in CS-exposed lung. Neonatal CS exposure caused durable structural and functional changes in the adult lung but did not potentiate CS-induced COPD changes. Cornified envelope protein gene expression was decreased in all CS-exposed mice, whereas myosin and erythrocyte gene expression was increased in mice exposed to both neonatal and adult CS, suggesting an adaptive response. Additional studies may be warranted to determine the utility of these genes as biomarkers of respiratory outcomes. PMID:21649527

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maneckjee, R.; Minna, J.D.

Using specific radioactively-labeled ligands, the authors find that lung cancer cell lines of diverse histologic types express multiple, high-affinity membrane receptors for {mu}, {delta}, and {kappa} opioid agonists and for nicotine and {alpha}-bungarotoxin. These receptors are biologically active because cAMP levels decreased in lung cancer cells after opioid and nicotine application. Nicotine at concentrations found in the blood of smokers had no effect on in vitro lung cancer cell growth, whereas {mu}, {delta}, and {kappa} opioid agonists at low concentrations inhibited lung cancer growth in vitro. They also found that lung cancer cells expressed various combinations of immunoreactive opioid peptidesmore » ({beta}-endorphin, enkephalin, or dynorphin), suggesting the participation of opioids in a negative autocrine loop or tumor-suppressing system. Due to the almost universal exposure of patients with lung cancer to nicotine, they tested whether nicotine affected the response of lung cancer cell growth to opioids and found that nicotine at concentrations of 100-200 nM partially or totally reversed opioid-induced growth inhibition in 9/14 lung cancer cell lines. These in vitro results for lung cancer cells suggest that opioids could function as part of a tumor suppressor system and that nicotine can function to circumvent this system in the pathogenesis of lung cancer.« less

Air Pollution and Lung Function in Minority Youth with Asthma in the GALA II (Genes-Environments and Admixture in Latino Americans) and SAGE II (Study of African Americans, Asthma, Genes, and Environments) Studies.

PubMed

Neophytou, Andreas M; White, Marquitta J; Oh, Sam S; Thakur, Neeta; Galanter, Joshua M; Nishimura, Katherine K; Pino-Yanes, Maria; Torgerson, Dara G; Gignoux, Christopher R; Eng, Celeste; Nguyen, Elizabeth A; Hu, Donglei; Mak, Angel C; Kumar, Rajesh; Seibold, Max A; Davis, Adam; Farber, Harold J; Meade, Kelley; Avila, Pedro C; Serebrisky, Denise; Lenoir, Michael A; Brigino-Buenaventura, Emerita; Rodriguez-Cintron, William; Bibbins-Domingo, Kirsten; Thyne, Shannon M; Williams, L Keoki; Sen, Saunak; Gilliland, Frank D; Gauderman, W James; Rodriguez-Santana, Jose R; Lurmann, Fred; Balmes, John R; Eisen, Ellen A; Burchard, Esteban G

2016-06-01

Adverse effects of exposures to ambient air pollution on lung function are well documented, but evidence in racial/ethnic minority children is lacking. To assess the relationship between air pollution and lung function in minority children with asthma and possible modification by global genetic ancestry. The study population consisted of 1,449 Latino and 519 African American children with asthma from five different geographical regions in the mainland United States and Puerto Rico. We examined five pollutants (particulate matter ≤10 μm and ≤2.5 μm in diameter, ozone, nitrogen dioxide, and sulfur dioxide), derived from participant residential history and ambient air monitoring data, and assessed over several time windows. We fit generalized additive models for associations between pollutant exposures and lung function parameters and tested for interaction terms between exposures and genetic ancestry. A 5 μg/m(3) increase in average lifetime particulate matter less than or equal to 2.5 μm in diameter exposure was associated with a 7.7% decrease in FEV1 (95% confidence interval = -11.8 to -3.5%) in the overall study population. Global genetic ancestry did not appear to significantly modify these associations, but percent African ancestry was a significant predictor of lung function. Early-life particulate exposures were associated with reduced lung function in Latino and African American children with asthma. This is the first study to report an association between exposure to particulates and reduced lung function in minority children in which racial/ethnic status was measured by ancestry-informative markers.

Aspergillus fumigatus chronic colonization and lung function decline in cystic fibrosis may have a two-way relationship.

PubMed

Noni, M; Katelari, A; Dimopoulos, G; Doudounakis, S-E; Tzoumaka-Bakoula, C; Spoulou, V

2015-11-01

Aspergillus fumigatus is commonly found in cystic fibrosis (CF) airways. Our aim was to assess the relationship between A. fumigatus chronic colonization and lung function in CF patients. A case-control study of CF patients born from 1989 to 2002 was performed. Medical records were reviewed from the time of initial diagnosis until December 2013. Chronic colonization was defined as two or more positive sputum cultures in a given year. Each patient chronically colonized with A. fumigatus was matched with three control patients (never colonized by A. fumigatus) for age, sex, and year of birth (±3 years). A number of parameters were recorded and analyzed prospectively. The primary outcome measure was the difference in forced expiratory volume in 1 s (FEV1) in percent predicted between groups. Linear mixed models were used for longitudinal analyses to evaluate the relationship between A. fumigatus chronic colonization and lung function during a 7-year period and study the lung function 4 years before the time of enrollment (t0). Twenty patients had chronic colonization and were matched with 60 controls. A significant difference in lung function was detected throughout the 7-year period after adjustment for confounders (est = 8.66, p = 0.020). Four years before t0, FEV1 baseline was the only factor associated with the course of lung function (est = 0.64, p < 0.001) and was significantly different between groups (p = 0.001). In conclusion, a decreased FEV1 baseline appears to be a risk factor for chronic colonization by A. fumigatus, which, in turn, may cause a faster deterioration of lung function.

Sepsis-Induced Coagulation in the Baboon Lung Is Associated with Decreased Tissue Factor Pathway Inhibitor

PubMed Central

Tang, Haiwang; Ivanciu, Lacramioara; Popescu, Narcis; Peer, Glenn; Hack, Erik; Lupu, Cristina; Taylor, Fletcher B.; Lupu, Florea

2007-01-01

Increased tissue factor (TF)-dependent procoagulant activity in sepsis may be partly due to decreased expression or function of tissue factor pathway inhibitor (TFPI). To test this hypothesis, baboons were infused with live Escherichia coli and sacrificed after 2, 8, or 24 hours. Confocal and electron microscopy revealed increased leukocyte infiltration and fibrin deposition in the intravascular and interstitial compartments. Large amounts of TF were detected by immunostaining in leukocytes and platelet-rich microthrombi. TF induction was documented by quantitative reverse transcriptase-polymerase chain reaction, enzyme-linked immunosorbent assay, and coagulation assays. Lung-associated TFPI antigen and mRNA decreased during sepsis, and TFPI activity diminished abruptly at 2 hours. Blocking antibodies against TFPI increased fibrin deposition in septic baboon lungs, suggesting that TF-dependent coagulation might be aggravated by reduced endothelial TFPI. Decreased TFPI activity coincided with the release of tissue plasminogen activator and the peak of plasmin generation, suggesting that TFPI could undergo proteolytic inactivation by plasmin. Enhanced plasmin produced in septic baboons by infusion of blocking antibodies against plasminogen activator inhibitor-1 led to decreased lung-associated TFPI and unforeseen massive fibrin deposition. We conclude that activation of TF-driven coagulation not adequately countered by TFPI may underlie the widespread thrombotic complications of sepsis. PMID:17640967

cAMP signalling decreases p300 protein levels by promoting its ubiquitin/proteasome dependent degradation via Epac and p38 MAPK in lung cancer cells.

PubMed

Jeong, Min-Jae; Kim, Eui-Jun; Cho, Eun-Ah; Ye, Sang-Kyu; Kang, Gyeong Hoon; Juhnn, Yong-Sung

2013-05-02

The transcriptional coactivator p300 functions as a histone acetyltransferase and a scaffold for transcription factors. We investigated the effect of cAMP signalling on p300 expression. The activation of cAMP signalling by the expression of constitutively active Gαs or by treatment with isoproterenol decreased the p300 protein expression in lung cancer cells. Isoproterenol promoted the ubiquitination and subsequent proteasomal degradation of p300 in an Epac-dependent manner. Epac promoted p300 degradation by inhibiting the activity of p38 MAPK. It is concluded that cAMP signalling decreases the level of the p300 protein by promoting its ubiquitin-proteasome dependent degradation, which is mediated by Epac and p38 MAPK, in lung cancer cells. Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Clinical measures, smoking, radon exposure, and risk of lung cancer in uranium miners.

PubMed Central

Finkelstein, M M

1996-01-01

OBJECTIVES: Exposure to the radioactive daughters of radon is associated with increased risk of lung cancer in mining populations. An investigation of incidence of lung cancer following a clinical survey of Ontario uranium miners was undertaken to explore whether risk associated with radon is modified by factors including smoking, radiographic silicosis, clinical symptoms, the results of lung function testing, and the temporal pattern of radon exposure. METHODS: Miners were examined in 1974 by a respiratory questionnaire, tests of lung function, and chest radiography. A random selection of 733 (75%) of the original 973 participants was followed up by linkage to the Ontario Mortality and Cancer Registries. RESULTS: Incidence of lung cancer was increased threefold. Risk of lung cancer among miners who had stopped smoking was half that of men who continued to smoke. There was no interaction between smoking and radon exposure. Men with lung function test results consistent with airways obstruction had an increased risk of lung cancer, even after adjustment for cigarette smoking. There was no association between radiographic silicosis and risk of lung cancer. Lung cancer was associated with exposures to radon daughters accumulated in a time window four to 14 years before diagnosis, but there was little association with exposures incurred earlier than 14 years before diagnosis. Among the men diagnosed with lung cancer, the mean and median dose rates were 2.6 working level months (WLM) a year and 1.8 WLM/year in the four to 14 year exposure window. CONCLUSIONS: Risk of lung cancer associated with radon is modified by dose and time from exposure. Risk can be substantially decreased by stopping smoking. PMID:8943835

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

PubMed

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

2005-10-01

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

The effect of oxidative stress polymorphisms on the association between long-term black carbon exposure and lung function among elderly men.

PubMed

Mordukhovich, Irina; Lepeule, Johanna; Coull, Brent A; Sparrow, David; Vokonas, Pantel; Schwartz, Joel

2015-02-01

Black carbon (BC) is a pro-oxidant, traffic-related pollutant linked with lung function decline. We evaluated the influence of genetic variation in the oxidative stress pathway on the association between long-term BC exposure and lung function decline. Lung function parameters (FVC and FEV1) were measured during one or more study visits between 1995 and 2011 (n=651 participants) among an elderly cohort: the Normative Aging Study. Residential BC exposure levels were estimated using a spatiotemporal land use regression model. We evaluated whether oxidative stress variants, combined into a genetic score, modify the association between 1-year and 5-year moving averages of BC exposure and lung function levels and rates of decline, using linear mixed models. We report stronger associations between long-term BC exposure and increased rate of lung function decline, but not baseline lung function level, among participants with higher oxidative stress allelic risk profiles compared with participants with lower risk profiles. Associations were strongest when evaluating 5-year moving averages of BC exposure. A 0.5 µg/m(3) increase in 5-year BC exposure was associated with a 0.1% yearly increase in FVC (95% CI -0.5 to 0.7) among participants with low genetic risk scores and a 1.3% yearly decrease (95% CI -1.8 to -0.8) among those with high scores (p-interaction=0.0003). Our results suggest that elderly men with high oxidative stress genetic scores may be more susceptible to the effects of BC on lung function decline. The results, if confirmed, should inform air-quality recommendations in light of a potentially susceptible subgroup. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Clinical value of Pro-GRP and T lymphocyte subpopulation for the assessment of immune functions of lung cancer patients after DC-CIK biological therapy.

PubMed

He, Lijie; Wang, Jing; Chang, Dandan; Lv, Dandan; Li, Haina; Zhang, Heping

2018-02-01

The present study investigated the aptness of assessing the levels of progastrin-releasing peptide (Pro-GRP) in addition to the T lymphocyte subpopulation in lung cancer patients prior to and after therapy for determining immune function. A total of 45 patients with lung cancer were recruited and stratified in to a non-small cell lung cancer (NSCLC) and an SCLC group. Prior to and after treatment by combined biological therapy comprising chemotherapy or chemoradiotherapy followed by three cycles of retransformation of autologous dendritic cells-cytokine-induced killer cells (DC-CIK), the peripheral blood was assessed for populations of CD3 + , CD4 + , CD8 + and regulatory T cells (Treg) by flow cytometry, and for the levels of pro-GRP, carcinoembryonic antigen, neuron-specific enolase and Cyfra 21-1. The results revealed that in NSCLC patients, CD8 + T lymphocytes and Treg populations were decreased, and that CD3 + and CD4 + T lymphocytes as well as the CD4 + /CD8 + ratio were increased after therapy; in SCLC patients, CD3 + , CD4 + and CD8 + T lymphocytes were increased, while Treg cells were decreased after treatment compared with those at baseline. In each group, Pro-GRP was decreased compared with that prior to treatment, and in the SCLC group only, an obvious negative correlation was identified between Pro-GRP and the T lymphocyte subpopulation. Furthermore, a significant correlation between Pro-GRP and Tregs was identified in each group. In conclusion, the present study revealed that the immune function of the patients was improved after biological therapy. The results suggested a significant correlation between Pro-GRP and the T lymphocyte subpopulation in SCLC patients. Detection of Pro-GRP may assist the early clinical diagnosis of SCLC and may also be used to assess the immune regulatory function of patients along with the T lymphocyte subpopulation. Biological therapy with retransformed autologous DC-CIK was indicated to enhance the specific elimination of tumor cells and improve the immune surveillance function in cancer patients, and also restrained the immune evasion of the tumor, leading to decreased Pro-GRP levels.

Testosterone Attenuates Group 2 Innate Lymphoid Cell-Mediated Airway Inflammation.

PubMed

Cephus, Jacqueline-Yvonne; Stier, Matthew T; Fuseini, Hubaida; Yung, Jeffrey A; Toki, Shinji; Bloodworth, Melissa H; Zhou, Weisong; Goleniewska, Kasia; Zhang, Jian; Garon, Sarah L; Hamilton, Robert G; Poloshukin, Vasiliy V; Boyd, Kelli L; Peebles, R Stokes; Newcomb, Dawn C

2017-11-28

Sex hormones regulate many autoimmune and inflammatory diseases, including asthma. As adults, asthma prevalence is 2-fold greater in women compared to men. The number of group 2 innate lymphoid cells (ILC2) is increased in patients with asthma, and we investigate how testosterone attenuates ILC2 function. In patients with moderate to severe asthma, we determine that women have an increased number of circulating ILC2 compared to men. ILC2 from adult female mice have increased IL-2-mediated ILC2 proliferation versus ILC2 from adult male mice, as well as pre-pubescent females and males. Further, 5α-dihydrotestosterone, a hormone downstream of testosterone, decreases lung ILC2 numbers and IL-5 and IL-13 expression from ILC2. In vivo, testosterone attenuated Alternaria-extract-induced IL-5+ and IL-13+ ILC2 numbers and lung eosinophils by intrinsically decreasing lung ILC2 numbers, as well as by decreasing expression of IL-33 and thymic stromal lymphopoietin (TSLP), ILC2-stimulating cytokines. Collectively, these findings provide a foundational understanding of sexual dimorphism in ILC2 function. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

A randomized double-blind crossover study of indoor air filtration and acute changes in cardiorespiratory health in a First Nations community.

PubMed

Weichenthal, S; Mallach, G; Kulka, R; Black, A; Wheeler, A; You, H; St-Jean, M; Kwiatkowski, R; Sharp, D

2013-06-01

Few studies have examined indoor air quality in First Nations communities and its impact on cardiorespiratory health. To address this need, we conducted a crossover study on a First Nations reserve in Manitoba, Canada, including 37 residents in 20 homes. Each home received an electrostatic air filter and a placebo filter for 1 week in random order, and lung function, blood pressure, and endothelial function measures were collected at the beginning and end of each week. Indoor air pollutants were monitored throughout the study period. Indoor PM2.5 decreased substantially during air filter weeks relative to placebo (mean difference: 37 μg/m(3) , 95% CI: 10, 64) but remained approximately five times greater than outdoor concentrations owing to a high prevalence of indoor smoking. On average, air filter use was associated with a 217-ml (95% CI: 23, 410) increase in forced expiratory volume in 1 s, a 7.9-mm Hg (95% CI: -17, 0.82) decrease in systolic blood pressure, and a 4.5-mm Hg (95% CI: -11, 2.4) decrease in diastolic blood pressure. Consistent inverse associations were also observed between indoor PM2.5 and lung function. In general, our findings suggest that reducing indoor PM2.5 may contribute to improved lung function in First Nations communities. Indoor air quality is known to contribute to adverse cardiorespiratory health, but few studies have examined indoor air quality in First Nations communities. Our findings suggest that indoor PM2.5 may contribute to reduced lung function and that portable air filters may help to alleviate these effects by effectively reducing indoor levels of particulate matter. © Her Majesty the Queen in Right of Canada 2012. Reproduced with the permission of the Minister of Health Canada.

The effect of donor treatment with hydrogen on lung allograft function in rats.

PubMed

Kawamura, Tomohiro; Huang, Chien-Sheng; Peng, Ximei; Masutani, Kosuke; Shigemura, Norihisa; Billiar, Timothy R; Okumura, Meinoshin; Toyoda, Yoshiya; Nakao, Atsunori

2011-08-01

Because inhaled hydrogen provides potent anti-inflammatory and antiapoptotic effects against acute lung injury, we hypothesized that treatment of organ donors with inhaled hydrogen during mechanical ventilation would decrease graft injury after lung transplantation. Orthotopic left lung transplants were performed using a fully allogeneic Lewis to Brown Norway rat model. The donors were exposed to mechanical ventilation with 98% oxygen plus 2% nitrogen or 2% hydrogen for 3 h prior to harvest, and the lung grafts underwent 4 h of cold storage in Perfadex (Vitrolife, Göteborg, Sweden). The graft function, histomorphologic changes, and inflammatory reactions were assessed. The combination of mechanical ventilation and prolonged cold ischemia resulted in marked deterioration of gas exchange when the donors were ventilated with 2% nitrogen/98% oxygen, which was accompanied by upregulation of proinflammatory cytokines and proapoptotic molecules. These lung injuries were attenuated significantly by ventilation with 2% hydrogen. Inhaled hydrogen induced heme oxygenase-1, an antioxidant enzyme, in the lung grafts prior to implantation, which might contribute to protective effects afforded by hydrogen. Preloaded hydrogen gas during ventilation prior to organ procurement protected lung grafts effectively from ischemia/reperfusion-induced injury in a rat lung transplantation model. Copyright © 2011 Mosby, Inc. All rights reserved.

Depletion of tissue plasminogen activator attenuates lung ischemia-reperfusion injury via inhibition of neutrophil extravasation.

PubMed

Zhao, Yunge; Sharma, Ashish K; LaPar, Damien J; Kron, Irving L; Ailawadi, Gorav; Liu, Yuan; Jones, David R; Laubach, Victor E; Lau, Christine L

2011-05-01

Ischemia-reperfusion (IR) injury following lung transplantation remains a major source of early morbidity and mortality. Histologically, this inflammatory process is characterized by neutrophil infiltration and activation. We previously reported that lung IR injury was significantly attenuated in plasminogen activator inhibitor-1-deficient mice. In this study, we explored the potential role of tissue plasminogen activator (tPA) in a mouse lung IR injury model. As a result, tPA knockout (KO) mice were significantly protected from lung IR injury through several mechanisms. At the cellular level, tPA KO specifically blocked neutrophil extravasation into the interstitium, and abundant homotypic neutrophil aggregation (HNA) was detected in the lung microvasculature of tPA KO mice after IR. At the molecular level, inhibition of neutrophil extravasation was associated with reduced expression of platelet endothelial cell adhesion molecule-1 mediated through the tPA/ LDL receptor-related protein/NF-κB signaling pathway, whereas increased P-selectin triggered HNA. At the functional level, tPA KO mice incurred significantly decreased vascular permeability and improved lung function following IR. Protection from lung IR injury in tPA KO mice occurs through a fibrinolysis-independent mechanism. These results suggest that tPA could serve as an important therapeutic target for the prevention and treatment of acute IR injury after lung transplantation.

Endothelin-1–Rho kinase interactions impair lung structure and cause pulmonary hypertension after bleomycin exposure in neonatal rat pups

PubMed Central

Tseng, Nancy; Seedorf, Gregory; Kuhn, Katherine; Abman, Steven H.

2016-01-01

Bronchopulmonary dysplasia (BPD) is the chronic lung disease associated with premature birth, characterized by impaired vascular and alveolar growth. In neonatal rats bleomycin decreases lung growth and causes pulmonary hypertension (PH), which is poorly responsive to nitric oxide. In the developing lung, through Rho kinase (ROCK) activation, ET-1 impairs endothelial cell function; however, whether ET-1–ROCK interactions contribute to impaired vascular and alveolar growth in experimental BPD is unknown. Neonatal rats were treated daily with intraperitoneal bleomycin with and without selective ETA (BQ123/BQ610) and ETB (BQ788) receptor blockers, nonselective ET receptor blocker (ETRB) (bosentan), or fasudil (ROCK inhibitor). At day 14, lungs were harvested for morphometrics, and measurements of Fulton's index (RV/LV+S), medial wall thickness (MWT), and vessel density. Lung ET-1 protein and ROCK activity (phospho-MYPT-1:total MYPT-1 ratio) were also measured by Western blot analysis. Bleomycin increased lung ET-1 protein expression by 65%, RV/LV+S by 60%, mean linear intercept (MLI) by 212%, and MWT by 140% and decreased radial alveolar count (RAC) and vessel density by 40 and 44%, respectively (P < 0.01 for each comparison). After bleomycin treatment, fasudil and bosentan partially restored RAC and vessel density and decreased MLI, RV/LV+S, and MWT to normal values. Bleomycin increased ROCK activity by 120%, which was restored to normal values by bosentan but not selective ETRB. We conclude that ET-1–ROCK interactions contribute to decreased alveolar and vascular growth and PH in experimental BPD. We speculate that nonselective ETRB and ROCK inhibitors may be effective in the treatment of infants with BPD and PH. PMID:27760762

Endothelin-1-Rho kinase interactions impair lung structure and cause pulmonary hypertension after bleomycin exposure in neonatal rat pups.

PubMed

Gien, Jason; Tseng, Nancy; Seedorf, Gregory; Kuhn, Katherine; Abman, Steven H

2016-12-01

Bronchopulmonary dysplasia (BPD) is the chronic lung disease associated with premature birth, characterized by impaired vascular and alveolar growth. In neonatal rats bleomycin decreases lung growth and causes pulmonary hypertension (PH), which is poorly responsive to nitric oxide. In the developing lung, through Rho kinase (ROCK) activation, ET-1 impairs endothelial cell function; however, whether ET-1-ROCK interactions contribute to impaired vascular and alveolar growth in experimental BPD is unknown. Neonatal rats were treated daily with intraperitoneal bleomycin with and without selective ET A (BQ123/BQ610) and ET B (BQ788) receptor blockers, nonselective ET receptor blocker (ETRB) (bosentan), or fasudil (ROCK inhibitor). At day 14, lungs were harvested for morphometrics, and measurements of Fulton's index (RV/LV+S), medial wall thickness (MWT), and vessel density. Lung ET-1 protein and ROCK activity (phospho-MYPT-1:total MYPT-1 ratio) were also measured by Western blot analysis. Bleomycin increased lung ET-1 protein expression by 65%, RV/LV+S by 60%, mean linear intercept (MLI) by 212%, and MWT by 140% and decreased radial alveolar count (RAC) and vessel density by 40 and 44%, respectively (P < 0.01 for each comparison). After bleomycin treatment, fasudil and bosentan partially restored RAC and vessel density and decreased MLI, RV/LV+S, and MWT to normal values. Bleomycin increased ROCK activity by 120%, which was restored to normal values by bosentan but not selective ETRB. We conclude that ET-1-ROCK interactions contribute to decreased alveolar and vascular growth and PH in experimental BPD. We speculate that nonselective ETRB and ROCK inhibitors may be effective in the treatment of infants with BPD and PH. Copyright © 2016 the American Physiological Society.

Erythropoietin-Derived Peptide Protects Against Acute Lung Injury After Rat Traumatic Brain Injury.

PubMed

Liu, Yuan; Lu, Junyu; Wang, Xiaoya; Chen, Liu; Liu, Su; Zhang, Zhiren; Yao, Wei

2017-01-01

Traumatic brain injury (TBI) can be complicated by TBI-triggered acute lung injury (ALI), in which inflammation plays a central role. It has been reported that an Erythropoietin-derived peptide (pHBSP) was able to ameliorate TBI; however, its function in TBI-caused ALI has not been reported yet. In this study, we studied the effect of pHBSP on TBI-caused ALI by using a weight-drop induced TBI model. At 8 h and 24 h post-TBI, pulmonary edema (PE) and bronchoalveolar lavage fluid (BALF) proteins were measured, and haematoxylin and eosin (H&E) staining of lung sections was carried out. At 24 h following TBI, the lungs were harvested for immunofluorescence staining and qRT-PCR analysis. At 8 h and 24 h post-TBI, pHBSP treatment significantly decreased wet/dry ratios, decreased total BALF protein, and attenuated the histological signs of pulmonary injury. At 24 h post-TBI, pHBSP treatment decreased the accumulation of CD68+ macrophages in the lung and reduced the mRNA levels of TNF-α, IL-6, IL-1β and iNOS in the lung. We identified the protective role that pHBSP played in TBI-caused ALI, suggesting that pHBSP is a potent candidate for systemic therapy in TBI patients. © 2017 The Author(s)Published by S. Karger AG, Basel.

Long-term gas exchange characteristics as markers of deterioration in patients with cystic fibrosis

PubMed Central

2009-01-01

Background and Aim In patients with cystic fibrosis (CF) the architecture of the developing lungs and the ventilation of lung units are progressively affected, influencing intrapulmonary gas mixing and gas exchange. We examined the long-term course of blood gas measurements in relation to characteristics of lung function and the influence of different CFTR genotype upon this process. Methods Serial annual measurements of PaO2 and PaCO2 assessed in relation to lung function, providing functional residual capacity (FRCpleth), lung clearance index (LCI), trapped gas (VTG), airway resistance (sReff), and forced expiratory indices (FEV1, FEF50), were collected in 178 children (88 males; 90 females) with CF, over an age range of 5 to 18 years. Linear mixed model analysis and binary logistic regression analysis were used to define predominant lung function parameters influencing oxygenation and carbon dioxide elimination. Results PaO2 decreased linearly from age 5 to 18 years, and was mainly associated with FRCpleth, (p < 0.0001), FEV1 (p < 0.001), FEF50 (p < 0.002), and LCI (p < 0.002), indicating that oxygenation was associated with the degree of pulmonary hyperinflation, ventilation inhomogeneities and impeded airway function. PaCO2 showed a transitory phase of low PaCO2 values, mainly during the age range of 5 to 12 years. Both PaO2 and PaCO2 presented with different progression slopes within specific CFTR genotypes. Conclusion In the long-term evaluation of gas exchange characteristics, an association with different lung function patterns was found and was closely related to specific genotypes. Early examination of blood gases may reveal hypocarbia, presumably reflecting compensatory mechanisms to improve oxygenation. PMID:19909502

Self-reported physical activity and lung function two months after cardiac surgery – a prospective cohort study

PubMed Central

2014-01-01

Background Physical activity has well-established positive health-related effects. Sedentary behaviour has been associated with postoperative complications and mortality after cardiac surgery. Patients undergoing cardiac surgery often suffer from impaired lung function postoperatively. The association between physical activity and lung function in cardiac surgery patients has not previously been reported. Methods Patients undergoing cardiac surgery were followed up two months postoperatively. Physical activity was assessed on a four-category scale (sedentary, moderate activity, moderate regular exercise, and regular activity and exercise), modified from the Swedish National Institute of Public Health’s national survey. Formal lung function testing was performed preoperatively and two months postoperatively. Results The sample included 283 patients (82% male). Two months after surgery, the level of physical activity had increased (p < 0.001) in the whole sample. Patients who remained active or increased their level of physical activity had significantly better recovery of lung function than patients who remained sedentary or had decreased their level of activity postoperatively in terms of vital capacity (94 ± 11% of preoperative value vs. 91 ± 9%; p = 0.03), inspiratory capacity (94 ± 14% vs. 88 ± 19%; p = 0.008), and total lung capacity (96 ± 11% vs. 90 ± 11%; p = 0.01). Conclusions An increased level of physical activity, compared to preoperative level, was reported as early as two months after surgery. Our data shows that there could be a significant association between physical activity and recovery of lung function after cardiac surgery. The relationship between objectively measured physical activity and postoperative pulmonary recovery needs to be further examined to verify these results. PMID:24678691

Mild Lung Restriction in Breast Cancer Patients After Hypofractionated and Conventional Radiation Therapy: A 3-Year Follow-Up

DOE Office of Scientific and Technical Information (OSTI.GOV)

Verbanck, Sylvia, E-mail: sylvia.verbanck@uzbrussel.be; Hanon, Shane; Schuermans, Daniel

Purpose: To assess the effect of radiation therapy on lung function over the course of 3 years. Methods and Materials: Evolution of restrictive and obstructive lung function parameters was investigated in 108 breast cancer participants in a randomized, controlled trial comparing conventional radiation therapy (CR) and hypofractionated tomotherapy (TT) (age at inclusion ranging 32-81 years). Spirometry, plethysmography, and hemoglobin-corrected diffusing capacity were assessed at baseline and after 3 months and 1, 2, and 3 years. Natural aging was accounted for by considering all lung function parameters in terms of percent predicted values using the most recent reference values for women aged up to 80 years. Results:more » In the patients with negligible history of respiratory disease or smoking (n=77), the greatest rate of functional decline was observed during the initial 3 months, this acute decrease being more marked in the CR versus the TT arm. During the remainder of the 3-year follow-up period, values (in terms of percent predicted) were maintained (diffusing capacity) or continued to decline at a slower rate (forced vital capacity). However, the average decline of the restrictive lung function parameters over a 3-year period did not exceed 9% predicted in either the TT or the CR arm. Obstructive lung function parameters remained unaffected throughout. Including also the 31 patients with a history of respiratory disease or more than 10 pack-years showed a very similar restrictive pattern. Conclusions: In women with breast cancer, both conventional radiation therapy and hypofractionated tomotherapy induce small but consistent restrictive lung patterns over the course of a 3-year period, irrespective of baseline respiratory status or smoking history. The fastest rate of lung function decline generally occurred in the first 3 months.« less

High risks of lung disease associated with early-life and moderate lifetime arsenic exposure in northern Chile.

PubMed

Steinmaus, Craig; Ferreccio, Catterina; Acevedo, Johanna; Balmes, John R; Liaw, Jane; Troncoso, Patricia; Dauphiné, David C; Nardone, Anthony; Smith, Allan H

2016-12-15

Arsenic in drinking water has been associated with increases in lung disease, but information on the long-term impacts of early-life exposure or moderate exposure levels are limited. We investigated pulmonary disease and lung function in 795 subjects from three socio-demographically similar areas in northern Chile: Antofagasta, which had a well-described period of high arsenic water concentrations (860μg/L) from 1958 to 1970; Iquique, which had long-term arsenic water concentrations near 60μg/L; and Arica, with long-term water concentrations ≤10μg/L. Compared to adults never exposed >10μg/L, adults born in Antofagasta during the high exposure period had elevated odds ratios (OR) of respiratory symptoms (e.g., OR for shortness of breath=5.56, 90% confidence interval (CI): 2.68-11.5), and decreases in pulmonary function (e.g., 224mL decrease in forced vital capacity in nonsmokers, 90% CI: 97-351mL). Subjects with long-term exposure to arsenic water concentrations near 60μg/L also had increases in some pulmonary symptoms and reduced lung function. Overall, these findings provide new evidence that in utero or childhood arsenic exposure is associated with non-malignant pulmonary disease in adults. They also provide preliminary new evidence that long-term exposures to moderate levels of arsenic may be associated with lung toxicity, although the magnitude of these latter findings were greater than expected and should be confirmed. Copyright © 2016 Elsevier Inc. All rights reserved.

High risks of lung disease associated with early-life and moderate lifetime arsenic exposure in northern Chile

PubMed Central

Steinmaus, Craig; Ferreccio, Catterina; Acevedo, Johanna; Balmes, John R; Liaw, Jane; Troncoso, Patricia; Dauphiné, David C; Nardone, Anthony; Smith, Allan H

2016-01-01

Background Arsenic in drinking water has been associated with increases in lung disease, but information on the long-term impacts of early-life exposure or moderate exposure levels are limited. Methods We investigated pulmonary disease and lung function in 795 subjects from three socio-demographically similar areas in northern Chile: Antofagasta, which had a well-described period of high arsenic water concentrations (860 μg/L) from 1958–1970; Iquique, which had long-term arsenic water concentrations near 60 μg/L; and Arica, with long-term water concentrations ≤10 μg/L. Results Compared to adults never exposed >10 μg/L, adults born in Antofagasta during the high exposure period had elevated odds ratios (OR) of respiratory symptoms (e.g., OR for shortness of breath = 5.56, 90% confidence interval (CI): 2.68–11.5), and decreases in pulmonary function (e.g., 224 ml decrease in forced vital capacity in nonsmokers, 90% CI: 97–351 ml). Subjects with long-term exposure to arsenic water concentrations near 60 μg/L also had increases in some pulmonary symptoms and reduced lung function. Conclusions Overall, these findings provide new evidence that in utero or childhood arsenic exposure is associated with non-malignant pulmonary disease in adults. They also provide preliminary new evidence that long-term exposures to moderate levels of arsenic may be associated with lung toxicity, although the magnitude of these latter findings were greater than expected and should be confirmed. PMID:27725189

Intrapulmonary receptors in the Tegu lizard: I. Sensitivity to CO2.

PubMed

Feede, M R; Kuhlmann, W D; Scheid, P

1977-02-01

Single unit vagal recordings from intrapulmonary receptors were obtained in decerebrate, paralyzed lizards both during pump ventilation and during unidirectional ventilation on the cannulated, sack-shaped lung. Two types of receptors were identified: (1) CO2-receptors, which increased their discharge frequency as intrapulmonary CO2 concentration decreased but were not sensitive to stretch of the lung. (2) Mechanoreceptors, which rapidly increased discharge frequency when the lung was stretched. These receptors' CO2 sensitivity varied. Lungs of lizards thus appeared to possess both CO2 receptors, which have functional characteristics similar to those in birds, and mechanoreceptors with properties similar to stretch receptors in mammals.

High risks of lung disease associated with early-life and moderate lifetime arsenic exposure in northern Chile

DOE Office of Scientific and Technical Information (OSTI.GOV)

Steinmaus, Craig, E-mail: craigs@berkeley.edu

Background: Arsenic in drinking water has been associated with increases in lung disease, but information on the long-term impacts of early-life exposure or moderate exposure levels are limited. Methods: We investigated pulmonary disease and lung function in 795 subjects from three socio-demographically similar areas in northern Chile: Antofagasta, which had a well-described period of high arsenic water concentrations (860 μg/L) from 1958 to 1970; Iquique, which had long-term arsenic water concentrations near 60 μg/L; and Arica, with long-term water concentrations ≤ 10 μg/L. Results: Compared to adults never exposed > 10 μg/L, adults born in Antofagasta during the high exposuremore » period had elevated odds ratios (OR) of respiratory symptoms (e.g., OR for shortness of breath = 5.56, 90% confidence interval (CI): 2.68–11.5), and decreases in pulmonary function (e.g., 224 mL decrease in forced vital capacity in nonsmokers, 90% CI: 97–351 mL). Subjects with long-term exposure to arsenic water concentrations near 60 μg/L also had increases in some pulmonary symptoms and reduced lung function. Conclusions: Overall, these findings provide new evidence that in utero or childhood arsenic exposure is associated with non-malignant pulmonary disease in adults. They also provide preliminary new evidence that long-term exposures to moderate levels of arsenic may be associated with lung toxicity, although the magnitude of these latter findings were greater than expected and should be confirmed. - Highlights: • Based on its unique geology, lifetime arsenic exposure can be assessed in north Chile. • Signs and symptoms of lung disease were associated with early-life arsenic exposure. • Evidence of lung disease was also associated with moderate arsenic exposure.« less

Calcineurin/Nfat signaling is required for perinatal lung maturation and function.

PubMed

Davé, Vrushank; Childs, Tawanna; Xu, Yan; Ikegami, Machiko; Besnard, Valérie; Maeda, Yutaka; Wert, Susan E; Neilson, Joel R; Crabtree, Gerald R; Whitsett, Jeffrey A

2006-10-01

Pulmonary surfactant proteins and lipids are required for lung function after birth. Lung immaturity and resultant surfactant deficiency cause respiratory distress syndrome, a common disorder contributing to morbidity and mortality in preterm infants. Surfactant synthesis increases prior to birth in association with formation of the alveoli that mediate efficient gas exchange. To identify mechanisms controlling perinatal lung maturation, the Calcineurin b1 (Cnb1) gene was deleted in the respiratory epithelium of the fetal mouse. Deletion of Cnb1 caused respiratory failure after birth and inhibited the structural maturation of the peripheral lung. Synthesis of surfactant and a lamellar body-associated protein, ABC transporter A3 (ABCA3), was decreased prior to birth. Nuclear factor of activated T cells (Nfat) calcineurin-dependent 3 (Nfatc3), a transcription factor modulated by calcineurin, was identified as a direct activator of Sftpa, Sftpb, Sftpc, Abca3, Foxa1, and Foxa2 genes. The calcineurin/Nfat pathway controls the morphologic maturation of lungs prior to birth and regulates expression of genes involved in surfactant homeostasis that are critical for adaptation to air breathing.

Idiopathic Pulmonary Fibrosis: Gender-Age-Physiology Index Stage for Predicting Future Lung Function Decline.

PubMed

Salisbury, Margaret L; Xia, Meng; Zhou, Yueren; Murray, Susan; Tayob, Nabihah; Brown, Kevin K; Wells, Athol U; Schmidt, Shelley L; Martinez, Fernando J; Flaherty, Kevin R

2016-02-01

Idiopathic pulmonary fibrosis is a progressive lung disease with variable course. The Gender-Age-Physiology (GAP) Index and staging system uses clinical variables to stage mortality risk. It is unknown whether clinical staging predicts future decline in pulmonary function. We assessed whether the GAP stage predicts future pulmonary function decline and whether interval pulmonary function change predicts mortality after accounting for stage. Patients with idiopathic pulmonary fibrosis (N = 657) were identified retrospectively at three tertiary referral centers, and baseline GAP stages were assessed. Mixed models were used to describe average trajectories of FVC and diffusing capacity of the lung for carbon monoxide (Dlco). Multivariable Cox proportional hazards models were used to assess whether declines in pulmonary function ≥ 10% in 6 months predict mortality after accounting for GAP stage. Over a 2-year period, GAP stage was not associated with differences in yearly lung function decline. After accounting for stage, a 10% decrease in FVC or Dlco over 6 months independently predicted death or transplantation (FVC hazard ratio, 1.37; Dlco hazard ratio, 1.30; both, P ≤ .03). Patients with GAP stage 2 with declining pulmonary function experienced a survival profile similar to patients with GAP stage 3, with 1-year event-free survival of 59.3% (95% CI, 49.4-67.8) vs 56.9% (95% CI, 42.2-69.1). Baseline GAP stage predicted death or lung transplantation but not the rate of future pulmonary function decline. After accounting for GAP stage, a decline of ≥ 10% over 6 months independently predicted death or lung transplantation. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Indoor NO2 air pollution and lung function of professional cooks.

PubMed

Arbex, M A; Martins, L C; Pereira, L A A; Negrini, F; Cardoso, A A; Melchert, W R; Arbex, R F; Saldiva, P H N; Zanobetti, A; Braga, A L F

2007-04-01

Studies of cooking-generated NO2 effects are rare in occupational epidemiology. In the present study, we evaluated the lung function of professional cooks exposed to NO2 in hospital kitchens. We performed spirometry in 37 cooks working in four hospital kitchens and estimated the predicted FVC, FEV1 and FEF(25-75), based on age, sex, race, weight, and height, according to Knudson standards. NO2 measurements were obtained for 4 consecutive days during 4 different periods at 20-day intervals in each kitchen. Measurements were performed inside and outside the kitchens, simultaneously using Palm diffusion tubes. A time/exposure indicator was defined as representative of the cumulative exposure of each cook. No statistically significant effect of NO2 exposure on FVC was found. Each year of work as a cook corresponded to a decrease in predicted FEV1 of 2.5% (P = 0.046) for the group as a whole. When smoking status and asthma were included in the analysis the effect of time/exposure decreased about 10% and lost statistical significance. On predicted FEF(25-75), a decrease of 3.5% (P = 0.035) was observed for the same group and the inclusion of controllers for smoking status and asthma did not affect the effects of time/exposure on pulmonary function parameter. After a 10-year period of work as cooks the participants of the study may present decreases in both predicted FEV1 and FEF(25-75) that can reach 20 and 30%, respectively. The present study showed small but statistically significant adverse effects of gas stove exposure on the lung function of professional cooks.

Inflation with carbon monoxide in rat donor lung during cold ischemia phase ameliorates graft injury

PubMed Central

Meng, Chao; Ma, Liangjuan; Liu, Jinfeng; Cui, Xiaoguang; Liu, Rongfang; Xing, Jingchun

2015-01-01

Carbon monoxide (CO) attenuates lung ischemia reperfusion injury (IRI) via inhalation, and as an additive dissolved in flush/preservation solution. This study observed the effects of lung inflation with CO on lung graft function in the setting of cold ischemia. Donor lungs were inflated with 40% oxygen + 60% nitrogen (control group) or with 500 ppm CO + 40% oxygen + nitrogen (CO group) during the cold ischemia phase and were kept at 4℃ for 180 min. Recipients were sacrificed by exsanguinations at 180 min after reperfusion. Rats in the sham group had no transplantation and were performed as the recipients. Compared with the sham group, the oxygenation determined by blood gas analysis and the pressure–volume curves of the lung grafts decreased significantly, while the wet weight/dry weight (W/D) ratio, inflammatory reaction, oxidative stress, and cell apoptosis increased markedly (P < 0.05). However, compared to the control group, CO treatment improved the oxygenation (381 ± 58 vs. 308 ± 78 mm Hg) and the pressure–volume curves (15.8 ± 2.4 vs. 11.6 ± 1.7 mL/kg) (P < 0.05). The W/D ratio (4.6 ± 0.6) and the serum levels of interleukin-8 (279 ± 46 pg/mL) and tumor necrosis factor-α (377 ± 59 pg/mL) in the CO group decreased significantly compared to the control group (5.8 ± 0.8, 456 ± 63 pg/mL, and 520 ± 91 pg/mL) (P < 0.05). In addition, CO inflation also significantly decreased malondialdehyde activity and apoptotic cells in grafts, and increased the superoxide dismutase content. Briefly, CO inflation in donor lungs in the setting of cold ischemia attenuated lung IRI and improved the graft function compared with oxygen. PMID:26290141

Inflation with carbon monoxide in rat donor lung during cold ischemia phase ameliorates graft injury.

PubMed

Meng, Chao; Ma, Liangjuan; Liu, Jinfeng; Cui, Xiaoguang; Liu, Rongfang; Xing, Jingchun; Zhou, Huacheng

2016-02-01

Carbon monoxide (CO) attenuates lung ischemia reperfusion injury (IRI) via inhalation, and as an additive dissolved in flush/preservation solution. This study observed the effects of lung inflation with CO on lung graft function in the setting of cold ischemia. Donor lungs were inflated with 40% oxygen + 60% nitrogen (control group) or with 500 ppm CO + 40% oxygen + nitrogen (CO group) during the cold ischemia phase and were kept at 4℃ for 180 min. Recipients were sacrificed by exsanguinations at 180 min after reperfusion. Rats in the sham group had no transplantation and were performed as the recipients. Compared with the sham group, the oxygenation determined by blood gas analysis and the pressure-volume curves of the lung grafts decreased significantly, while the wet weight/dry weight (W/D) ratio, inflammatory reaction, oxidative stress, and cell apoptosis increased markedly (P < 0.05). However, compared to the control group, CO treatment improved the oxygenation (381 ± 58 vs. 308 ± 78 mm Hg) and the pressure-volume curves (15.8 ± 2.4 vs. 11.6 ± 1.7 mL/kg) (P < 0.05). The W/D ratio (4.6 ± 0.6) and the serum levels of interleukin-8 (279 ± 46 pg/mL) and tumor necrosis factor-α (377 ± 59 pg/mL) in the CO group decreased significantly compared to the control group (5.8 ± 0.8, 456 ± 63 pg/mL, and 520 ± 91 pg/mL) (P < 0.05). In addition, CO inflation also significantly decreased malondialdehyde activity and apoptotic cells in grafts, and increased the superoxide dismutase content. Briefly, CO inflation in donor lungs in the setting of cold ischemia attenuated lung IRI and improved the graft function compared with oxygen. © 2015 by the Society for Experimental Biology and Medicine.

COMPARATIVE SPIROMETRIC STUDIES BEFORE AND AFTER Co$sup 60$ IRRADIATION OF PATIENTS WITH BRONCHIAL CARCINOMA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lichterfeld, A.; Widow, W.; Zahnert, R.

1961-08-01

Changes in respiratory function were evaluated after radiotherapy in 46 patients with lung cancer. Spirometric tests were conducted shortly before irradiation and 4 to 6 weeks after local gamma -radiation doses of 3500 r delivered over 2 to 3 weeks. A few patients received 6000 r over 4 to 5 weeks, and 40 unirradiated controls were also examined. In general, respiratory function was diminished following irradiation. The disturbances were most marked in the group receiving the higher dose, in which vital capacity fell by an average of 728 cm/sup 3/ (25%) postirradiation. With lower doses the decrease was 7%. Themore » decrease was greater after irradiation of supraclavicular fields. In over half the cases, radiotherapy resulted in regression of the tumor and an improvement of radioinduced atelectasis, which sometimes resulted in an improvement in the Tiffeneau test values. Radiation injury in the lung could be detected radiographically in only 8 cases, indicating that spirometry and histologic examination are more sensitive means of detecting the injury. It was concluded that preoperative radiotherapy of lung cancer may impair the patient's chances for recovery because of the resulting disorders in pulmonary function. (TCO)« less

Decreased expression of monocarboxylate transporter 1 and 4 in the branching airway epithelium of nitrofen-induced congenital diaphragmatic hernia.

PubMed

Takahashi, Toshiaki; Friedmacher, Florian; Zimmer, Julia; Puri, Prem

2016-06-01

Monocarboxylate transporters (MCTs) are crucial for the maintenance of intracellular pH homeostasis in developing fetal lungs. MCT1/4 is strongly expressed by epithelial airway cells throughout lung branching morphogenesis. Functional inhibition of MCT1/4 in fetal rat lung explants has been shown to result in airway defects similar to pulmonary hypoplasia (PH) in congenital diaphragmatic hernia (CDH). We hypothesized that pulmonary expression of MCT1/4 is decreased during lung branching morphogenesis in the nitrofen model of CDH-associated PH. Timed-pregnant rats received nitrofen or vehicle on gestational day 9 (D9). Fetuses were harvested on D15, D18, and D21, and divided into control and nitrofen-exposed group. Pulmonary gene expression levels of MCT1/4 were analyzed by qRT-PCR. Immunofluorescence staining for MCT1/4 was combined with E-cadherin in order to evaluate protein expression in branching airway tissue. Relative mRNA levels of MCT1/4 were significantly reduced in lungs of nitrofen-exposed fetuses on D15, D18, and D21 compared to controls. Confocal laser scanning microscopy confirmed markedly decreased immunofluorescence of MCT1/4 in distal bronchial and primitive alveolar epithelium of nitrofen-exposed fetuses on D15, D18, and D21 compared to controls. Decreased expression of MCT1/4 in distal airway epithelium may disrupt lung branching morphogenesis and thus contribute to the development of PH in the nitrofen-induced CDH model. Copyright © 2016 Elsevier Inc. All rights reserved.

Lentivirus-ABCG1 instillation reduces lipid accumulation and improves lung compliance in GM-CSF knock-out mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Malur, Anagha; Huizar, Isham; Wells, Greg

2011-11-18

Highlights: Black-Right-Pointing-Pointer Lentivirus-ABCG1 reduces lipid accumulation in lungs of GM-CSF knock-out mice. Black-Right-Pointing-Pointer Up-regulation of ABCG1 improves lung function. Black-Right-Pointing-Pointer Upregulation of ABCG1 improves surfactant metabolism. -- Abstract: We have shown decreased expression of the nuclear transcription factor, peroxisome proliferator-activated receptor-gamma (PPAR{gamma}) and the PPAR{gamma}-regulated ATP-binding cassette transporter G1 (ABCG1) in alveolar macrophages from patients with pulmonary alveolar proteinosis (PAP). PAP patients also exhibit neutralizing antibodies to granulocyte-macrophage colony stimulating factor (GM-CSF), an upregulator of PPAR{gamma}. In association with functional GM-CSF deficiency, PAP lung is characterized by surfactant-filled alveolar spaces and lipid-filled alveolar macrophages. Similar pathology characterizes GM-CSF knock-out (KO)more » mice. We reported previously that intratracheal instillation of a lentivirus (lenti)-PPAR{gamma} plasmid into GM-CSF KO animals elevated ABCG1 and reduced alveolar macrophage lipid accumulation. Here, we hypothesized that instillation of lenti-ABCG1 might be sufficient to decrease lipid accumulation and improve pulmonary function in GM-CSF KO mice. Animals received intratracheal instillation of lenti-ABCG1 or control lenti-enhanced Green Fluorescent Protein (eGFP) plasmids and alveolar macrophages were harvested 10 days later. Alveolar macrophage transduction efficiency was 79% as shown by lenti-eGFP fluorescence. Quantitative PCR analyses indicated a threefold (p = 0.0005) increase in ABCG1 expression with no change of PPAR{gamma} or ABCA1 in alveolar macrophages of lenti-ABCG1 treated mice. ABCG1 was unchanged in control lenti-eGFP and PBS-instilled groups. Oil Red O staining detected reduced intracellular neutral lipid in alveolar macrophages from lenti-ABCG1 treated mice. Extracellular cholesterol and phospholipids were also decreased as shown by analysis of bronchoalveolar lavage fluid. Lung compliance was diminished in untreated GMCSF KO mice but improved significantly after lenti-ABCG1 treatment. Data demonstrate that in vivo instillation of lenti-ABCG1 in GM-CSF KO mice is sufficient to restore pulmonary homeostasis by: (1) upregulating ABCG1; (2) reducing intra and extracellular lipids; and (3) improving lung function. Results suggest that the ABCG1 lipid transporter is the key downstream target of GM-CSF-induced PPAR{gamma} necessary for surfactant catabolism.« less

Abnormal pulmonary function in adults with sickle cell anemia.

PubMed

Klings, Elizabeth S; Wyszynski, Diego F; Nolan, Vikki G; Steinberg, Martin H

2006-06-01

Pulmonary complications of sickle cell anemia (Hb-SS) commonly cause morbidity, yet few large studies of pulmonary function tests (PFTs) in this population have been reported. PFTs (spirometry, lung volumes, and diffusion capacity for carbon monoxide [DLCO]) from 310 adults with Hb-SS were analyzed to determine the pattern of pulmonary dysfunction and their association with other systemic complications of sickle cell disease. Raw PFT data were compared with predicted values. Each subject was subclassified into one of five groups: obstructive physiology, restrictive physiology, mixed obstructive/restrictive physiology, isolated low DLCO, or normal. The association between laboratory data of patients with decreased DLCO or restrictive physiology and those of normal subjects was assessed by multivariate linear regression. Normal PFTs were present in only 31 of 310 (10%) patients. Overall, adults with Hb-SS were characterized by decreased total lung capacities (70.2 +/- 14.7% predicted) and DLCO (64.5 +/- 19.9%). The most common PFT patterns were restrictive physiology (74%) and isolated low DLCO (13%). Decreased DLCO was associated with thrombocytosis (p = 0.05), with hepatic dysfunction (elevated alanine aminotransferase; p = 0.07), and a trend toward renal dysfunction (elevated blood urea nitrogen and creatinine; p = 0.05 and 0.07, respectively). Pulmonary function is abnormal in 90% of adult patients with Hb-SS. Common abnormalities include restrictive physiology and decreased DLCO. Decreased DLCO may indicate more severe sickle vasculopathy characterized by impaired hepatic and renal function.

Time-series analysis of lung texture on bone-suppressed dynamic chest radiograph for the evaluation of pulmonary function: a preliminary study

NASA Astrophysics Data System (ADS)

Tanaka, Rie; Matsuda, Hiroaki; Sanada, Shigeru

2017-03-01

The density of lung tissue changes as demonstrated on imagery is dependent on the relative increases and decreases in the volume of air and lung vessels per unit volume of lung. Therefore, a time-series analysis of lung texture can be used to evaluate relative pulmonary function. This study was performed to assess a time-series analysis of lung texture on dynamic chest radiographs during respiration, and to demonstrate its usefulness in the diagnosis of pulmonary impairments. Sequential chest radiographs of 30 patients were obtained using a dynamic flat-panel detector (FPD; 100 kV, 0.2 mAs/pulse, 15 frames/s, SID = 2.0 m; Prototype, Konica Minolta). Imaging was performed during respiration, and 210 images were obtained over 14 seconds. Commercial bone suppression image-processing software (Clear Read Bone Suppression; Riverain Technologies, Miamisburg, Ohio, USA) was applied to the sequential chest radiographs to create corresponding bone suppression images. Average pixel values, standard deviation (SD), kurtosis, and skewness were calculated based on a density histogram analysis in lung regions. Regions of interest (ROIs) were manually located in the lungs, and the same ROIs were traced by the template matching technique during respiration. Average pixel value effectively differentiated regions with ventilatory defects and normal lung tissue. The average pixel values in normal areas changed dynamically in synchronization with the respiratory phase, whereas those in regions of ventilatory defects indicated reduced variations in pixel value. There were no significant differences between ventilatory defects and normal lung tissue in the other parameters. We confirmed that time-series analysis of lung texture was useful for the evaluation of pulmonary function in dynamic chest radiography during respiration. Pulmonary impairments were detected as reduced changes in pixel value. This technique is a simple, cost-effective diagnostic tool for the evaluation of regional pulmonary function.

miR-34a Inhibits Lung Fibrosis by Inducing Lung Fibroblast Senescence.

PubMed

Cui, Huachun; Ge, Jing; Xie, Na; Banerjee, Sami; Zhou, Yong; Antony, Veena B; Thannickal, Victor J; Liu, Gang

2017-02-01

Cellular senescence has been implicated in diverse pathologies. However, there is conflicting evidence regarding the role of this process in tissue fibrosis. Although dysregulation of microRNAs is a key mechanism in the pathogenesis of lung fibrosis, it is unclear whether microRNAs function by regulating cellular senescence in the disease. In this study, we found that miR-34a demonstrated greater expression in the lungs of patients with idiopathic pulmonary fibrosis and in mice with experimental pulmonary fibrosis, with its primary localization in lung fibroblasts. More importantly, miR-34a was up-regulated significantly in both human and mouse lung myofibroblasts. We found that mice with miR-34a ablation developed more severe pulmonary fibrosis than did wild-type animals after fibrotic lung injury. Mechanistically, we found that miR-34a induced a senescent phenotype in lung fibroblasts because this microRNA increased senescence-associated β-galactosidase activity, enhanced expression of senescence markers, and decreased cell proliferative capacities. Consistently, we found that primary lung fibroblasts from fibrotic lungs of miR-34a-deficient mice had a diminished senescent phenotype and enhanced resistance to apoptosis as compared with those from wild-type animals. We also identified multiple miR-34a targets that likely mediated its activities in inducing senescence in lung fibroblasts. In conclusion, our data suggest that miR-34a functions through a negative feedback mechanism to restrain fibrotic response in the lungs by promoting senescence of pulmonary fibroblasts.

M2 polarization of macrophages facilitates arsenic-induced cell transformation of lung epithelial cells

PubMed Central

Li, Hui; Dai, Lu; Frank, Jacqueline A.; Peng, Shaojun; Wang, Siying; Chen, Gang

2017-01-01

The alterations in microenvironment upon chronic arsenic exposure may contribute to arsenic-induced lung carcinogenesis. Immune cells, such as macrophages, play an important role in mediating the microenvironment in the lungs. Macrophages carry out their functions after activation. There are two activation status for macrophages: classical (M1) or alternative (M2); the latter is associated with tumorigenesis. Our previous work showed that long-term arsenic exposure induces transformation of lung epithelial cells. However, the crosstalk between epithelial cells and macrophages upon arsenic exposure has not been investigated. In this study, using a co-culture system in which human lung epithelial cells are cultured with macrophages, we determined that long-term arsenic exposure polarizes macrophages towards M2 status through ROS generation. Co-culture with epithelial cells further enhanced the polarization of macrophages as well as transformation of epithelial cells, while blocking macrophage M2 polarization decreased the transformation. In addition, macrophage M2 polarization decreased autophagy activity, which may account for increased cell transformation of epithelial cells with co-culture of macrophages. PMID:28423485

SURFACTANT DYSFUNCTION IN LUNG CONTUSION WITH AND WITHOUT SUPERIMPOSED GASTRIC ASPIRATION IN A RAT MODEL

PubMed Central

Raghavendran, Krishnan; Davidson, Bruce A.; Knight, Paul R.; Wang, Zhengdong; Helinski, Jadwiga; Chess, Patricia R.; Notter, Robert H.

2009-01-01

This study investigates surfactant dysfunction in rats with lung contusion (LC) induced by blunt chest trauma. Rats at 24 h postcontusion had a decreased percent content of large surfactant aggregates in cell-free bronchoalveolar lavage (BAL) and altered large-aggregate composition with decreased phosphatidylcholine (PC), increased lyso-PC, and increased protein compared with uninjured controls. The surface activity of large aggregates on a pulsating bubble surfactometer was also severely impaired at 24 h postcontusion. Decreases in large surfactant aggregate content and surface activity were improved, but still apparent, at 48 and 72 h postcontusion compared with uninjured control rats and returned to normal by 96 h postcontusion. The functional importance of surfactant abnormalities in LC injury was documented in pilot studies showing that exogenous surfactant replacement at 24 h postcontusion improved inflation/deflation lung volumes. Additional experiments investigated a clinically relevant combination of LC plus gastric aspiration (combined acid and small gastric food particles) and found reductions in large surfactant aggregates in BAL similar to those for LC. However, rats given LC + combined acid and small gastric food particles versus LC had more severe surfactant dysfunction based on decreases in surface activity and alterations in large aggregate composition. Combined data for all animal groups had strong statistical correlations between surfactant dysfunction (increased minimum surface tension, decreased large aggregates in BAL, decreased aggregate PC, and increased aggregate lyso-PC) and the severity of inflammatory lung injury (increased total protein, albumin, protein/phospholipid ratio, neutrophils, and erythrocytes in BAL plus increased whole lung myeloperoxidase activity). These results show that surfactant dysfunction is important in the pathophysiology of LC with or without concurrent gastric aspiration and provides a rationale for surfactant replacement therapy in these prevalent clinical conditions. PMID:18323743

Association of generic health-related quality of life (EQ-5D dimensions) and inactivity with lung function in lung-healthy German adults: results from the KORA studies F4L and Age.

PubMed

Luzak, Agnes; Karrasch, Stefan; Wacker, Margarethe; Thorand, Barbara; Nowak, Dennis; Peters, Annette; Schulz, Holger

2018-03-01

Among patients with lung disease, decreased lung function is associated with lower health-related quality of life. However, whether this association is detectable within the physiological variability of respiratory function in lung-healthy populations is unknown. We analyzed the association of each EQ-5D-3L dimension (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) and self-reported physical inactivity with spirometric indices in lung-healthy adults. Modulating effects between inactivity and EQ-5D dimensions were considered. 1132 non-smoking, apparently lung-healthy participants (48% male, aged 64 ± 12 years) from the population-based KORA F4L and Age surveys in Southern Germany were analyzed. Associations of each EQ-5D dimension and inactivity with spirometric indices serving as outcomes (forced expiratory volume in 1 s (FEV 1 ), forced vital capacity (FVC), FEV 1 /FVC, and mid-expiratory flow) were examined by linear regression, considering possible confounders. Interactions between EQ-5D dimensions (no problems/any problems) and inactivity (four categories of time spent engaging in exercise: inactive to most active) were assessed. Among all participants 42% reported no problems in any EQ-5D dimension, 24% were inactive and 32% exercised > 2 h/week. After adjustment, FEV 1 was - 99 ml (95% CI - 166; - 32) and FVC was - 109 ml (95% CI - 195; - 24) lower among subjects with mobility problems. Comparable estimates were observed for usual activities. Inactivity was negatively associated with FVC (β-coefficient: - 83 ml, 95% CI - 166; 0), but showed no interactions with EQ-5D. Problems with mobility or usual activities, and inactivity were associated with slightly lower spirometric parameters in lung-healthy adults, suggesting a relationship between perceived physical functioning and volumetric lung function.

The Markers of Glutamate Metabolism in Peripheral Blood Mononuclear Cells and Neurological Complications in Lung Cancer Patients

PubMed Central

Ambrosius, Wojciech; Gazdulska, Joanna; Gołda-Gocka, Iwona; Kozubski, Wojciech; Ramlau, Rodryg

2016-01-01

Objective. To evaluate the involvement of glutamate metabolism in peripheral blood mononuclear cells (PBMC) in the development of neurological complications in lung cancer and during chemotherapy. Methods. The prospective study included 221 lung cancer patients treated with chemotherapeutics. Neurological status and cognitive functions were evaluated at baseline and after 6-month follow-up. Glutamate level, the activities of glutaminase- (GLS-) glutamate synthetizing enzyme, glutamate dehydrogenase (GDH), and glutamate decarboxylase catalyzing glutamate degradation were analyzed in PBMC and in sera of lung cancer patients by means of spectrophotometric and colorimetric methods. Results. Chemotherapy of lung neoplasms induced increase of glutamate content in PBMC and its concentration in serum increased the activity of GDH in PBMC and decreased activity of glutaminase in PBMC. The changes in glutamate metabolism markers were associated with initial manifestation of neurological deficit in lung cancer patients and with new symptoms, which appear as a complication of chemotherapy. Moreover, the analyzed parameters of glutamate control correlated with a spectrum of cognitive functions measures in lung cancer patients. Conclusion. We have demonstrated dysregulation in glutamate and glutamate metabolism controlling enzymes as promising indicators of risk for chemotherapy-induced neurological complications in lung cancer patients with particular emphasis on cognitive impairment. PMID:28044066

Evaluation of vulnerable PM2.5-exposure individuals: a repeated-measure study in an elderly population.

PubMed

Chu, Haiyan; Xin, Junyi; Yuan, Qi; Zhang, Xu; Pan, Wang; Zeng, Xinying; Chen, Yaoyao; Ma, Gaoxiang; Ge, Yuqiu; Du, Mulong; Tong, Na; Li, Xiaobo; Zhang, Zhengdong; Wang, Meilin

2018-04-01

Numerous studies have shown that elderly people are susceptible to high-level particles with aerodynamic diameter ≤ 2.5 μm (PM 2.5 ) exposure. However, not all elderly people exposed to PM 2.5 suffer from diseases. In this study, we aim to establish a method to predict the vulnerable PM 2.5 -exposure individuals among elderly population. Fourteen elderly people were recruited from May 8 to July 4, 2016, in Nanjing, China. Ten physiological indicators were repeatedly measured for 15 times. Liner mixed-effects model, principal component analysis (PCA), and PM 2.5 lag score were used to estimate the effects of PM 2.5 on blood pressure, pulse, and lung function. As a result, each quartile increase of ambient PM 2.5 was significantly associated with increased pulse (P < 0.05 for lag0, 1, 4, 0-1, 0-2, 0-3, and 0-5 days), decreased blood pressure (P < 0.05 for lag4 and 0-3 days), and decreased lung function (P < 0.05 for lag0, 1, 0-1, and 0-2 days) among the 14 elderly people. In terms of pulse or lung function, three elderly people were considered as vulnerable PM 2.5 -exposure individuals. No vulnerable individual was found for blood pressure. Blood pressure, pulse, and lung function could be affected by high-level PM 2.5 exposure in elderly people. This method for screening three elderly people may provide a new insight on identifying the vulnerable PM 2.5 -exposure individuals.

Dust is in the air. Part II: Effects of occupational exposure to welding fumes on lung function in a 9-year study.

PubMed

Haluza, Daniela; Moshammer, Hanns; Hochgatterer, Karl

2014-02-01

Adverse health effects of work-related contact with respirable hazardous substances are of great public interest. Because related prospective and long-term follow-up studies are rare, the extent of acute and chronic pulmonary health risks of occupational exposure to welding fumes is discussed controversially in the scientific literature. The objective of the present longitudinal study during a 9-year period was to investigate the annual changes of lung function in welders. Anthropometric measures and smoking behaviour, and spirometric tests (FVC, FEV1, and MEF50) obtained during routine occupational health checkups of female and male workers (n = 1,982) in Austria during the years 2002-2010 were analyzed. The study participants displayed average lung function values lower than the age- and sex-specific norm. Decrease in respiratory capacity was dependent on smoking habits and duration of occupational exposure. Specifically for welders (n = 1,326), decrease of pulmonary function was significantly associated with heavy smoking (FVC -70.7 ml, p = 0.07; FEV1 -167.4 ml, p < 0.001; MEF50 -356.2 ml/s, p < 0.001), but not with moderate smoking habits, and also with duration of occupational exposure to welding fumes per year (FVC -0.89 ml, p = 0.36; FEV1 -2.91 ml, p < 0.001; MEF50 -4.7 ml/s, p = 0.047). Individual smoking habits as well as duration of occupational exposure to welding fumes showed a negative impact on lung function parameters. To reduce the risk of work-associated respiratory morbidity, smoking cessation is highly recommended to personnel engaged in welding fumes- and dust-exposed occupations.

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

PubMed Central

Haider, Syed H.; Crowley, George; Lee, Audrey; Ebrahim, Minah; Zhang, Liqun; Chen, Lung-Chi; Gordon, Terry; Liu, Mengling; Prezant, David J.; Schmidt, Ann Marie

2017-01-01

World Trade Center-particulate matter(WTC-PM) exposure and metabolic-risk are associated with WTC-Lung Injury(WTC-LI). The receptor for advanced glycation end-products (RAGE) is most highly expressed in the lung, mediates metabolic risk, and single-nucleotide polymorphisms at the AGER-locus predict forced expiratory volume(FEV). Our objectives were to test the hypotheses that RAGE is a biomarker of WTC-LI in the FDNY-cohort and that loss of RAGE in a murine model would protect against acute PM-induced lung disease. We know from previous work that early intense exposure at the time of the WTC collapse was most predictive of WTC-LI therefore we utilized a murine model of intense acute PM-exposure to determine if loss of RAGE is protective and to identify signaling/cytokine intermediates. This study builds on a continuing effort to identify serum biomarkers that predict the development of WTC-LI. A case-cohort design was used to analyze a focused cohort of male never-smokers with normal pre-9/11 lung function. Odds of developing WTC-LI increased by 1.2, 1.8 and 1.0 in firefighters with soluble RAGE (sRAGE)≥97pg/mL, CRP≥2.4mg/L, and MMP-9≤397ng/mL, respectively, assessed in a multivariate logistic regression model (ROCAUC of 0.72). Wild type(WT) and RAGE-deficient(Ager-/-) mice were exposed to PM or PBS-control by oropharyngeal aspiration. Lung function, airway hyperreactivity, bronchoalveolar lavage, histology, transcription factors and plasma/BAL cytokines were quantified. WT-PM mice had decreased FEV and compliance, and increased airway resistance and methacholine reactivity after 24-hours. Decreased IFN-γ and increased LPA were observed in WT-PM mice; similar findings have been reported for firefighters who eventually develop WTC-LI. In the murine model, lack of RAGE was protective from loss of lung function and airway hyperreactivity and was associated with modulation of MAP kinases. We conclude that in a multivariate adjusted model increased sRAGE is associated with WTC-LI. In our murine model, absence of RAGE mitigated acute deleterious effects of PM and may be a biologically plausible mediator of PM-related lung disease. PMID:28926576

[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).

Ventilatory function in rubber processing workers: acute changes over the workshift.

PubMed

Governa, M; Comai, M; Valentino, M; Antonicelli, L; Rinaldi, F; Pisani, E

1987-02-01

When considering rubber tyre manufacturing from an occupational health viewpoint, three areas may be identified in which exposure to respirable materials are potentially harmful: the processing, curing, and talc areas. A study of the ventilatory function of the entire work force employed in the processing area in a rubber tyre manufacturing plant was undertaken to determine whether an acute reduction in lung function occurs over the course of their working shift (the plant worked a three shift system) and whether a chronic exposure to the occupational airborne contaminants causes permanent changes in lung function. The ventilatory function was measured at the worksite at the beginning and immediately after the end of the workshift. No evidence of chronic obstructive pulmonary disease was found and in most cases no significant decline in FEV1 was observed. Only one of the 79 individuals showed a moderate obstruction, measured by the ratio FEV1/FVC which gave the value of 0.55, with no variation over the shift. For non-smokers, the FVC, FEV1, and FEF25-75% were lower in those exposed for more than five years than in those exposed for five years or less. A similar pattern was also observed in the FVC and FEV1 of the smokers. None of these differences was statistically significant. Within each exposure group the pulmonary function of the smokers was lower than that of the non-smokers, but the only significant difference was found in the values of FEF25-75%. Only one man showed a decline in the FEV1/FVC ratio over the shift, but during each shift, a decrease in all the lung function tests was observed. The decrease was smallest during the first of the three shifts. These results are thought to support the hypothesis that there are acute adverse effects over an eight hour shift. Further investigations are needed to discover whether these acute changes in lung function result from a chemical stimulation or irritant receptors in the airways.

Effect of a smoking ban on respiratory health in nonsmoking hospitality workers: a prospective cohort study.

PubMed

Rajkumar, Sarah; Stolz, Daiana; Hammer, Jürg; Moeller, Alexander; Bauer, Georg F; Huynh, Cong Khanh; Röösli, Martin

2014-10-01

The aim of this study was to examine the effect of a smoking ban on lung function, fractional exhaled nitric oxide, and respiratory symptoms in nonsmoking hospitality workers. Secondhand smoke exposure at the workplace, spirometry, and fractional exhaled nitric oxide were measured in 92 nonsmoking hospitality workers before as well as twice after a smoking ban. At baseline, secondhand smoke-exposed hospitality workers had lung function values significantly below the population average. After the smoking ban, the covariate-adjusted odds ratio for cough was 0.59 (95% confidence interval, 0.36 to 0.93) and for chronic bronchitis 0.75 (95% confidence interval, 0.55 to 1.02) compared with the preban period. The below-average lung function before the smoking ban indicates chronic damages from long-term exposure. Respiratory symptoms such as cough decreased within 12 months after the ban.

Existence, functional impairment, and lung repair potential of endothelial colony-forming cells in oxygen-induced arrested alveolar growth.

PubMed

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

2014-05-27

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. 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. 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. © 2014 American Heart Association, Inc.

Increased Risk of Interstitial Lung Disease in Children with a Single R288K Variant of ABCA3

PubMed Central

Wittmann, Thomas; Frixel, Sabrina; Höppner, Stefanie; Schindlbeck, Ulrike; Schams, Andrea; Kappler, Matthias; Hegermann, Jan; Wrede, Christoph; Liebisch, Gerhard; Vierzig, Anne; Zacharasiewicz, Angela; Kopp, Matthias Volkmar; Poets, Christian F; Baden, Winfried; Hartl, Dominik; van Kaam, Anton H; Lohse, Peter; Aslanidis, Charalampos; Zarbock, Ralf; Griese, Matthias

2016-01-01

The ABCA3 gene encodes a lipid transporter in type II pneumocytes critical for survival and normal respiratory function. The frequent ABCA3 variant R288K increases the risk for neonatal respiratory distress syndrome among term and late preterm neonates, but its role in children’s interstitial lung disease has not been studied in detail. In a retrospective cohort study of 228 children with interstitial lung disease related to the alveolar surfactant system, the frequency of R288K was assessed and the phenotype of patients carrying a single R288K variant further characterized by clinical course, lung histology, computed tomography and bronchoalveolar lavage phosphatidylcholine PC 32:0. Cell lines stably transfected with ABCA3-R288K were analyzed for intracellular transcription, processing and targeting of the protein. ABCA3 function was assessed by detoxification assay of doxorubicin, and the induction and volume of lamellar bodies. We found nine children with interstitial lung disease carrying a heterozygous R288K variant, a frequency significantly higher than in the general Caucasian population. All identified patients had neonatal respiratory insufficiency, recovered and developed chronic interstitial lung disease with intermittent exacerbations during early childhood. In vitro analysis showed normal transcription, processing, and targeting of ABCA3-R288K, but impaired detoxification function and smaller lamellar bodies. We propose that the R288K variant can underlie interstitial lung disease in childhood due to reduced function of ABCA3, demonstrated by decelerated detoxification of doxorubicin, reduced PC 32:0 content and decreased lamellar body volume. PMID:26928390

Alveolar derecruitment and collapse induration as crucial mechanisms in lung injury and fibrosis.

PubMed

Lutz, Dennis; Gazdhar, Amiq; Lopez-Rodriguez, Elena; Ruppert, Clemens; Mahavadi, Poornima; Günther, Andreas; Klepetko, Walter; Bates, Jason H; Smith, Bradford; Geiser, Thomas; Ochs, Matthias; Knudsen, Lars

2015-02-01

Idiopathic pulmonary fibrosis (IPF) and bleomycin-induced pulmonary fibrosis are associated with surfactant system dysfunction, alveolar collapse (derecruitment), and collapse induration (irreversible collapse). These events play undefined roles in the loss of lung function. The purpose of this study was to quantify how surfactant inactivation, alveolar collapse, and collapse induration lead to degradation of lung function. Design-based stereology and invasive pulmonary function tests were performed 1, 3, 7, and 14 days after intratracheal bleomycin-instillation in rats. The number and size of open alveoli was correlated to mechanical properties. Active surfactant subtypes declined by Day 1, associated with a progressive alveolar derecruitment and a decrease in compliance. Alveolar epithelial damage was more pronounced in closed alveoli compared with ventilated alveoli. Collapse induration occurred on Day 7 and Day 14 as indicated by collapsed alveoli overgrown by a hyperplastic alveolar epithelium. This pathophysiology was also observed for the first time in human IPF lung explants. Before the onset of collapse induration, distal airspaces were easily recruited, and lung elastance could be kept low after recruitment by positive end-expiratory pressure (PEEP). At later time points, the recruitable fraction of the lung was reduced by collapse induration, causing elastance to be elevated at high levels of PEEP. Surfactant inactivation leading to alveolar collapse and subsequent collapse induration might be the primary pathway for the loss of alveoli in this animal model. Loss of alveoli is highly correlated with the degradation of lung function. Our ultrastructural observations suggest that collapse induration is important in human IPF.

[Lung dysfunction in patients with mild chronic obstructive bronchitis].

PubMed

Nefedov, V B; Popova, L A; Shergina, E A

2004-01-01

VC, FVC, FEV1, FEV1/VC%, PEF, MEF25, MEF50, MEF75, TCL, TGV, RV, Ravt, Riin, Rex, DLCO-SS, PaO2, and PaO2 were determined in 33 patients with mild chronic obstructive lung disease (FEV1 > 70% of the normal value). All the patients were found to have impaired bronchial patency; most (63.6%) patients had lung volume and capacity changes, almost half (45.5%) the patients had pulmonary gas exchange dysfunction. Impaired bronchial patency mainly appeared as decreased MEF50, MEF15, and FEV1/VC%; altered lung volumes and capacities manifested chiefly by increased RV and decreased VC; pulmonary gas exchange dysfunction showed up primarily as lowered PaO2. The magnitude of the observed functional changes was generally slight. MEF50, MEF75, FEV1/VC%, and VC dropped to 59-20 and 79-70% of the normal value, respectively. RV increased up to 142-196% of the normal value; PaO2 reduced up to 79-60% mm Hg.

Depletion of tissue plasminogen activator attenuates lung ischemia-reperfusion injury via inhibition of neutrophil extravasation

PubMed Central

Zhao, Yunge; Sharma, Ashish K.; LaPar, Damien J.; Kron, Irving L.; Ailawadi, Gorav; Liu, Yuan; Jones, David R.; Laubach, Victor E.

2011-01-01

Ischemia-reperfusion (IR) injury following lung transplantation remains a major source of early morbidity and mortality. Histologically, this inflammatory process is characterized by neutrophil infiltration and activation. We previously reported that lung IR injury was significantly attenuated in plasminogen activator inhibitor-1-deficient mice. In this study, we explored the potential role of tissue plasminogen activator (tPA) in a mouse lung IR injury model. As a result, tPA knockout (KO) mice were significantly protected from lung IR injury through several mechanisms. At the cellular level, tPA KO specifically blocked neutrophil extravasation into the interstitium, and abundant homotypic neutrophil aggregation (HNA) was detected in the lung microvasculature of tPA KO mice after IR. At the molecular level, inhibition of neutrophil extravasation was associated with reduced expression of platelet endothelial cell adhesion molecule-1 mediated through the tPA/ LDL receptor-related protein/NF-κB signaling pathway, whereas increased P-selectin triggered HNA. At the functional level, tPA KO mice incurred significantly decreased vascular permeability and improved lung function following IR. Protection from lung IR injury in tPA KO mice occurs through a fibrinolysis-independent mechanism. These results suggest that tPA could serve as an important therapeutic target for the prevention and treatment of acute IR injury after lung transplantation. PMID:21378024

Quantification of atopy, lung function and airway hypersensitivity in adults

PubMed Central

2011-01-01

Background Studies in children have shown that concentration of specific serum IgE (sIgE) and size of skin tests to inhalant allergens better predict wheezing and reduced lung function than the information on presence or absence of atopy. However, very few studies in adults have investigated the relationship of quantitative atopy with lung function and airway hyperresponsiveness (AHR). Objective To determine the association between lung function and AHR and quantitative atopy in a large sample of adults from the UK. Methods FEV1 and FVC (% predicted) were measured using spirometry and airway responsiveness by methacholine challenge (5-breath dosimeter protocol) in 983 subjects (random sample of 800 parents of children enrolled in a population-based birth cohort enriched with 183 patients with physician-diagnosed asthma). Atopic status was assessed by skin prick tests (SPT) and measurement of sIgE (common inhalant allergens). We also measured indoor allergen exposure in subjects' homes. Results Spirometry was completed by 792 subjects and 626 underwent methacholine challenge, with 100 (16.0%) having AHR (dose-response slope>25). Using sIgE as a continuous variable in a multiple linear regression analysis, we found that increasing levels of sIgE to mite, cat and dog were significantly associated with lower FEV1 (mite p = 0.001, cat p = 0.0001, dog p = 2.95 × 10-8). Similar findings were observed when using the size of wheal on skin testing as a continuous variable, with significantly poorer lung function with increasing skin test size (mite p = 8.23 × 10-8, cat p = 3.93 × 10-10, dog p = 3.03 × 10-15, grass p = 2.95 × 10-9). The association between quantitative atopy with lung function and AHR remained unchanged when we repeated the analyses amongst subjects defined as sensitised using standard definitions (sIgE>0.35 kUa/l, SPT-3 mm>negative control). Conclusions In the studied population, lung function decreased and AHR increased with increasing sIgE levels or SPT wheal diameter to inhalant allergens, suggesting that atopy may not be a dichotomous outcome influencing lung function and AHR. PMID:22410099

Quantification of Age-Related Lung Tissue Mechanics under Mechanical Ventilation.

PubMed

Kim, JongWon; Heise, Rebecca L; Reynolds, Angela M; Pidaparti, Ramana M

2017-09-29

Elderly patients with obstructive lung diseases often receive mechanical ventilation to support their breathing and restore respiratory function. However, mechanical ventilation is known to increase the severity of ventilator-induced lung injury (VILI) in the elderly. Therefore, it is important to investigate the effects of aging to better understand the lung tissue mechanics to estimate the severity of ventilator-induced lung injuries. Two age-related geometric models involving human bronchioles from generation G10 to G23 and alveolar sacs were developed. The first is for a 50-year-old (normal) and second is for an 80-year old (aged) model. Lung tissue mechanics of normal and aged models were investigated under mechanical ventilation through computational simulations. Results obtained indicated that lung tissue strains during inhalation (t = 0.2 s) decreased by about 40% in the alveolar sac (G23) and 27% in the bronchiole (G20), respectively, for the 80-year-old as compared to the 50-year-old. The respiratory mechanics parameters (work of breathing per unit volume and maximum tissue strain) over G20 and G23 for the 80-year-old decreased by about 64% (three-fold) and 80% (four-fold), respectively, during the mechanical ventilation breathing cycle. However, there was a significant increase (by about threefold) in lung compliance for the 80-year-old in comparison to the 50-year-old. These findings from the computational simulations demonstrated that lung mechanical characteristics are significantly compromised in aging tissues, and these effects were quantified in this study.

The RNA binding protein tristetraprolin down-regulates autophagy in lung adenocarcinoma cells.

PubMed

Dong, Fei; Li, Cen; Wang, Pu; Deng, Xiaoya; Luo, Qinli; Tang, Xiaokui; Xu, Li

2018-06-01

Tristetraprolin (TTP) is the most well-known member of RNA-binding zinc-finger protein that play a significant role in accelerating mRNA decay. Increasingly studies have reported that TTP was functioned as a tumor suppressor gene in several types of carcinomas, while its underlying mechanism is not clear yet. In the current study, we found that TTP overexpression decreased cell proliferation and increased cell death in lung adenocarcinoma cells, with the cell cycle arrest at the S phase. Remarkably, instead of inducing cell apoptosis directly, TTP overexpression alters cell autophagy. Our studies demonstrate that TTP overexpression has no effect on apoptosis related genes, but decreases the expression of autophagy-related genes, including Beclin 1 and LC3II. The level of autophagy flux assessed by infection with the mGFP-RFP-LC3 adenovirus construction has been blocked by TTP overexpression. Moreover, the autophagic vacuoles number detected by transmission electron microscopy decreased with TTP expression up-regulation. Our results indicate, for the first time, that TTP suppresses cell proliferation and increases cell death through cell autophagy pathway in lung cancer cells. Our study provides a new angle of view for TTP function as a tumor suppressor which could be targeted in tumor treatment. Copyright © 2018 Elsevier Inc. All rights reserved.

Lung function and airway inflammation in rats following exposure to combustion products of carbon-graphite/epoxy composite material: comparison to a rodent model of acute lung injury.

PubMed

Whitehead, Gregory S; Grasman, Keith A; Kimmel, Edgar C

2003-02-01

Pulmonary function and inflammation in the lungs of rodents exposed by inhalation to carbon/graphite/epoxy advanced composite material (ACM) combustion products were compared to that of a rodent model of acute lung injury (ALI) produced by pneumotoxic paraquat dichloride. This investigation was undertaken to determine if short-term exposure to ACM smoke induces ALI; and to determine if smoke-related responses were similar to the pathogenic mechanisms of a model of lung vascular injury. We examined the time-course for mechanical lung function, infiltration of inflammatory cells into the lung, and the expression of three inflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha), macrophage inflammatory protein-2 (MIP-2) and interferon-gamma (IFN-gamma). Male Fischer-344 rats were either exposed to 26.8-29.8 g/m(3) nominal concentrations of smoke or were given i.p. injections of paraquat dichloride. Measurements were determined at 1, 2, 3, and 7 days post exposure. In the smoke-challenged rats, there were no changes in lung function indicative of ALI throughout the 7-day observation period, despite the acute lethality of the smoke atmosphere. However, the animals showed signs of pulmonary inflammation. The expression of TNF-alpha was significantly increased in the lavage fluid 1 day following exposure, which preceded the maximum leukocyte infiltration. MIP-2 levels were significantly increased in lavage fluid at days 2, 3, and 7. This followed the leukocyte infiltration. IFN-gamma was significantly increased in the lung tissue at day 7, which occurred during the resolution of the inflammatory response. The paraquat, which was also lethal to a small percentage of the animals, caused several physiologic changes characteristic of ALI, including significant decreases in lung compliance, lung volumes/capacities, distribution of ventilation, and gas exchange capacity. The expression of TNF-alpha and MIP-2 increased significantly in the lung tissue as well as in the lavage fluid. Increased MIP-2 levels also preceded the maximum neutrophil infiltration. The differences in the time-course and primary site of TNF-alpha, MIP-2, and IFN-gamma expression; and the differences in the temporal relationship between their expression and infiltration of inflammatory cells may have accounted for the differences in lung function between paraquat treated and ACM smoke exposed animals.

Dielectric properties of lung tissue as a function of air content.

PubMed

Nopp, P; Rapp, E; Pfützner, H; Nakesch, H; Ruhsam, C

1993-06-01

Dielectric measurements were made on lung samples with different electrode systems in the frequency range 5 kHz-100 kHz. In the case of plate electrodes and spot electrodes, the effects of electrode polarization were partly corrected. An air filling factor F is defined, which is determined from the mass and volume of the sample. The results indicate that the electrical properties of lung tissue are highly dependent on the condition of the tissue. Furthermore they show that the conductivity sigma as well as the relative permittivity epsilon r decreases with increasing F. This is discussed using histological material. Using a simple theoretical model, the decrease of sigma and epsilon r is explained by the thinning of the alveolar walls as well as by the deformation of the epithelial cells and blood vessels through the expansion of the alveoli.

Controlled lung reperfusion to reduce pulmonary ischaemia/reperfusion injury after cardiopulmonary bypass in a porcine model.

PubMed

Slottosch, Ingo; Liakopoulos, Oliver; Kuhn, Elmar; Deppe, Antje; Lopez-Pastorini, Alberto; Schwarz, David; Neef, Klaus; Choi, Yeong-Hoon; Sterner-Kock, Anja; Jung, Kristina; Mühlfeld, Christian; Wahlers, Thorsten

2014-12-01

Ischaemia/reperfusion (I/R) injury of the lungs contributes to pulmonary dysfunction after cardiac surgery with cardiopulmonary bypass (CPB), leading to increased morbidity and mortality of patients. This study investigated the value of controlled lung reperfusion strategies on lung ischaemia-reperfusion injury in a porcine CPB model. Pigs were subjected to routine CPB for 120 min with 60 min of blood cardioplegic cardiac arrest (CCA). Following CCA, the uncontrolled reperfusion (UR, n = 6) group was conventionally weaned from CPB. Two groups underwent controlled lung reperfusion strategies (CR group: controlled reperfusion conditions, n = 6; MR group: controlled reperfusion conditions and modified reperfusate, n = 6) via the pulmonary artery before CPB weaning. Sham-operated pigs (n = 7) served as controls. Animals were followed up until 4 h after CPB. Pulmonary function, haemodynamics, markers of inflammation, endothelial injury and oxidative stress as well as morphological lung alterations were analysed. CPB (UR group) induced deterioration of pulmonary function (lung mechanics, oxygenation index and lung oedema). Also, controlled lung reperfusion groups (CR and MR) presented with pulmonary dysfunction after CPB. However, compared with UR, controlled lung reperfusion strategies (CR and MR) improved lung mechanics and reduced markers of oxidative stress, but without alteration of haemodynamics, oxygenation, inflammation, endothelial injury and lung morphology. Both controlled reperfusion groups were similar without relevant differences. Controlled lung reperfusion strategies attenuated a decrease in lung mechanics and an increase in oxidative stress, indicating an influence on CPB-related pulmonary injury. However, they failed to avoid completely CPB-related lung injury, implying the need for additional strategies given the multifactorial pathophysiology of postoperative pulmonary dysfunction. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Implication of Sarcopenia and Sarcopenic Obesity on Lung Function in Healthy Elderly: Using Korean National Health and Nutrition Examination Survey.

PubMed

Moon, Ji Hyun; Kong, Mi Hee; Kim, Hyeon Ju

2015-11-01

Previous studies have demonstrated a positive association between obesity and decreased lung function. However, the effect of muscle and fat has not been fully assessed, especially in a healthy elderly population. In this study, we evaluated the impact of low muscle mass (LMM) and LMM with obesity on pulmonary impairment in healthy elderly subjects. Our study used data from the Korea National Health and Nutrition Examination Survey from 2008 to 2011. Men and women aged 65 yr or older were included. Muscle mass was measured by dual-energy X-ray absorptiometry. LMM was defined as two standard deviations below the sex-specific mean for young healthy adults. Obesity was defined as body mass index ≥ 25 kg/m(2). The prevalence of LMM in individuals aged over 65 was 11.9%. LMM and pulmonary function (forced vital capacity and forced expiratory volume in 1 second) were independently associated after adjusting for age, sex, body mass index, smoking status, alcohol consumption, and frequency of exercise. LMM with obesity was also related to a decrease in pulmonary function. This study revealed that LMM is an independent risk factor of decreased pulmonary function in healthy Korean men and women over 65 yr of age.

Impact of obstructive sleep apnea on lung volumes and mechanical properties of the respiratory system in overweight and obese individuals.

PubMed

Abdeyrim, Arikin; Zhang, Yongping; Li, Nanfang; Zhao, Minghua; Wang, Yinchun; Yao, Xiaoguang; Keyoumu, Youledusi; Yin, Ting

2015-07-25

Even through narrowing of the upper-airway plays an important role in the generation of obstructive sleep apnea (OSA), the peripheral airways is implicated in pre-obese and obese OSA patients, as a result of decreased lung volume and increased lung elastic recoil pressure, which, in turn, may aggravate upper-airway collapsibility. A total of 263 male (n = 193) and female (n = 70) subjects who were obese to various degrees without a history of lung diseases and an expiratory flow limitation, but troubled with snoring or suspicion of OSA were included in this cross-sectional study. According to nocturnal-polysomnography the subjects were distributed into OSA and non-OSA groups, and were further sub-grouped by gender because of differences between males and females, in term of, lung volume size, airway resistance, and the prevalence of OSA among genders. Lung volume and respiratory mechanical properties at different-frequencies were evaluated by plethysmograph and an impulse oscillation system, respectively. Functional residual capacity (FRC) and expiratory reserve volume were significantly decreased in the OSA group compared to the non-OSA group among males and females. As weight and BMI in males in the OSA group were greater than in the non-OSA group (90 ± 14.8 kg vs. 82 ± 10.4 kg, p < 0.001; 30.5 ± 4.2 kg/m(2) vs. 28.0 ± 3.0 kg/m(2), p < 0.001), multiple regression analysis was required to adjust for BMI or weight and demonstrated that these lung volumes decreases were independent from BMI and associated with the severity of OSA. This result was further confirmed by the female cohort. Significant increases in total respiratory resistance and decreases in respiratory conductance (Grs) were observed with increasing severity of OSA, as defined by the apnea-hypopnea index (AHI) in both genders. The specific Grs (sGrs) stayed relatively constant between the two groups in woman, and there was only a weak association between AHI and sGrs among man. Multiple-stepwise-regression showed that reactance at 5 Hz was highly correlated with AHI in males and females or hypopnea index in females, independently-highly correlated with peripheral-airway resistance and significantly associated with decreasing FRC. Total respiratory resistance and peripheral airway resistance significantly increase, and its inverse Grs decrease, in obese patients with OSA in comparison with those without OSA, and are independently associated with OSA severity. These results might be attributed to the abnormally increased lung elasticity recoil pressure on exhalation, due to increase in lung elasticity and decreased lung volume in obese OSA.

Expression of Sproutys and SPREDs is decreased during lung branching morphogenesis in nitrofen-induced pulmonary hypoplasia.

PubMed

Friedmacher, Florian; Gosemann, Jan-Hendrik; Fujiwara, Naho; Takahashi, Hiromizu; Hofmann, Alejandro; Puri, Prem

2013-11-01

Pulmonary hypoplasia (PH) is a life-threatening condition associated with congenital diaphragmatic hernia (CDH), characterized by defective lung development. Sproutys and Sprouty-related proteins (SPREDs) play a key role in lung branching morphogenesis through modification of epithelial-mesenchymal interactions. During the pseudoglandular stage, Sproutys are highly expressed in distal airway epithelium, while SPREDs within the surrounding mesenchyme. Sprouty2/4 knockouts show severe defects in branching morphogenesis with reduced number of distal airways. SPRED-1 and SPRED-2 are strongly expressed in regions of new airway formation, highlighting their important function in branching pattern. We hypothesized that expression of Sprouty2, Sprouty4, SPRED-1 and SPRED-2 is decreased during lung branching morphogenesis in nitrofen-induced PH. Timed-pregnant rats received either nitrofen or vehicle on E9.5. On E15.5 (n = 16), fetal lungs were micro-dissected and divided into controls and PH, while on E18.5 (n = 24) groups were: control, PH without CDH [CDH(-)], and PH with CDH [CDH(+)]. Pulmonary gene expression levels of Sprouty2, Sprouty4, SPRED-1 and SPRED-2 were analyzed by qRT-PCR. Immunohistochemistry was performed to evaluate protein expression/distribution. On E18.5, relative mRNA expression levels of Sprouty2, Sprouty4, SPRED-1 and SPRED-2 were significantly decreased in CDH(-) and CDH(+) groups compared to controls (P < 0.05). Immunoreactivity of Sprouty2, Sprouty4, SPRED-1 and SPRED-2 was markedly diminished on E18.5 in nitrofen-induced PH. Decreased expression of Sproutys and SPREDs during the terminal pseudoglandular stage may disrupt lung branching morphogenesis by interfering with epithelial-mesenchymal interactions contributing to PH.

No effect of elevated operating lung volumes on airway function during variable workrate exercise in asthmatic humans.

PubMed

Klansky, Andrew; Irvin, Charlie; Morrison-Taylor, Adriane; Ahlstrand, Sarah; Labrie, Danielle; Haverkamp, Hans Christian

2016-07-01

In asthmatic adults, airway caliber fluctuates during variable intensity exercise such that bronchodilation (BD) occurs with increased workrate whereas bronchoconstriction (BC) occurs with decreased workrate. We hypothesized that increased lung mechanical stretch would prevent BC during such variable workrate exercise. Ten asthmatic and ten nonasthmatic subjects completed two exercise trials on a cycle ergometer. Both trials included a 28-min exercise bout consisting of alternating four min periods at workloads equal to 40 % (Low) and 70% (High) peak power output. During one trial, subjects breathed spontaneously throughout exercise (SVT), such that tidal volume (VT) and end-inspiratory lung volume (EILV) were increased by 0.5 and 0.6 liters during the high compared with the low workload in nonasthmatic and asthmatic subjects, respectively. During the second trial (MVT), VT and EILV were maintained constant when transitioning from the high to the low workload. Forced exhalations from total lung capacity were performed during each exercise workload. In asthmatic subjects, forced expiratory volume 1.0 s (FEV1.0) increased and decreased with the increases and decreases in workrate during both SVT (Low, 3.3 ± 0.3 liters; High, 3.6 ± 0.2 liters; P < 0.05) and MVT (Low, 3.3 ± 0.3 liters; High, 3.5 ± 0.2 liters; P < 0.05). Thus increased lung stretch during MVT did not prevent decreases in airway caliber when workload was reduced. We conclude that neural factors controlling airway smooth muscle (ASM) contractile activity during whole body exercise are more robust determinants of airway caliber than the ability of lung stretch to alter ASM actin-myosin binding and contraction. Copyright © 2016 the American Physiological Society.

DIETARY OMEGA-3 FATTY ACIDS MODIFIED THE ASSOCIATION OF PULMONARY FUNCTION WITH AIR POLLUTION IN ADOLESCENTS

EPA Science Inventory

Previous children's studies in North America and Germany have shown that ambient sulfate particles are associated with an increased prevalence of bronchitis and decreased lung function. We have now investigated the ability of dietary intake of anti-inflammatory omega-3 fatty aci...

Elemental composition of particulate matter and the association with lung function.

PubMed

Eeftens, Marloes; Hoek, Gerard; Gruzieva, Olena; Mölter, Anna; Agius, Raymond; Beelen, Rob; Brunekreef, Bert; Custovic, Adnan; Cyrys, Josef; Fuertes, Elaine; Heinrich, Joachim; Hoffmann, Barbara; de Hoogh, Kees; Jedynska, Aleksandra; Keuken, Menno; Klümper, Claudia; Kooter, Ingeborg; Krämer, Ursula; Korek, Michal; Koppelman, Gerard H; Kuhlbusch, Thomas A J; Simpson, Angela; Smit, Henriëtte A; Tsai, Ming-Yi; Wang, Meng; Wolf, Kathrin; Pershagen, Göran; Gehring, Ulrike

2014-09-01

Negative effects of long-term exposure to particulate matter (PM) on lung function have been shown repeatedly. Spatial differences in the composition and toxicity of PM may explain differences in observed effect sizes between studies. We conducted a multicenter study in 5 European birth cohorts-BAMSE (Sweden), GINIplus and LISAplus (Germany), MAAS (United Kingdom), and PIAMA (The Netherlands)-for which lung function measurements were available for study subjects at the age of 6 or 8 years. Individual annual average residential exposure to copper, iron, potassium, nickel, sulfur, silicon, vanadium, and zinc within PM smaller than 2.5 μm (PM2.5) and smaller than 10 μm (PM10) was estimated using land-use regression models. Associations between air pollution and lung function were analyzed by linear regression within cohorts, adjusting for potential confounders, and then combined by random effects meta-analysis. We observed small reductions in forced expiratory volume in the first second, forced vital capacity, and peak expiratory flow related to exposure to most elemental pollutants, with the most substantial negative associations found for nickel and sulfur. PM10 nickel and PM10 sulfur were associated with decreases in forced expiratory volume in the first second of 1.6% (95% confidence interval = 0.4% to 2.7%) and 2.3% (-0.1% to 4.6%) per increase in exposure of 2 and 200 ng/m, respectively. Associations remained after adjusting for PM mass. However, associations with these elements were not evident in all cohorts, and heterogeneity of associations with exposure to various components was larger than for exposure to PM mass. Although we detected small adverse effects on lung function associated with annual average levels of some of the evaluated elements (particularly nickel and sulfur), lower lung function was more consistently associated with increased PM mass.

Vitamin C to Decrease the Effects of Smoking in Pregnancy on Infant Lung Function (VCSIP): Rationale, design, and methods of a randomized, controlled trial of vitamin C supplementation in pregnancy for the primary prevention of effects of in utero tobacco smoke exposure on infant lung function and respiratory health.

PubMed

McEvoy, Cindy T; Milner, Kristin F; Scherman, Ashley J; Schilling, Diane G; Tiller, Christina J; Vuylsteke, Brittany; Shorey-Kendrick, Lyndsey E; Spindel, Eliot R; Schuff, Robert; Mitchell, Julie; Peters, Dawn; Metz, Jill; Haas, David; Jackson, Keith; Tepper, Robert S; Morris, Cynthia D

2017-07-01

Despite strong anti-smoking efforts, at least 12% of American women cannot quit smoking when pregnant resulting in >450,000 smoke-exposed infants born yearly. Smoking during pregnancy is the largest preventable cause of childhood respiratory illness including wheezing and asthma. Recent studies have shown a protective effect of vitamin C supplementation on the lung function of offspring exposed to in utero smoke in a non-human primate model and an initial human trial. Vitamin C to Decrease the Effects of Smoking in Pregnancy on Infant Lung Function (VCSIP) is a randomized, double-blind, placebo-controlled trial to evaluate pulmonary function at 3months of age in infants delivered to pregnant smokers randomized to 500mg/day of vitamin C versus placebo during pregnancy. Secondary aims evaluate the incidence of wheezing through 12months and pulmonary function testing at 12months of age. Women are randomized between 13 and 23weeks gestation from clinical sites in Portland, Oregon at Oregon Health & Science University and PeaceHealth Southwest Medical Center and in Indianapolis, Indiana at Indiana University and Wishard Hospital. Vitamin C supplementation occurs from randomization to delivery. Monthly contact with participants and monitoring of medical records is performed to document medication adherence, changes in smoking and medical history, and adverse events. Pulmonary function testing of offspring occurs at 3 and 12months of age and incidence of wheezing and respiratory illness through 12months is captured via at least quarterly questionnaires. Ancillary studies are investigating the impact of vitamin C on placental blood flow and DNA methylation. Copyright © 2017 Elsevier Inc. All rights reserved.

Genetic Ancestry-Smoking Interactions and Lung Function in African Americans: A Cohort Study

PubMed Central

Colangelo, Laura A.; Williams, L. Keoki; Sen, Saunak; Kritchevsky, Stephen B.; Meibohm, Bernd; Galanter, Joshua; Hu, Donglei; Gignoux, Christopher R.; Liu, Yongmei; Harris, Tamara B.; Ziv, Elad; Zmuda, Joseph; Garcia, Melissa; Leak, Tennille S.; Foreman, Marilyn G.; Smith, Lewis J.; Fornage, Myriam; Liu, Kiang; Burchard, Esteban G.

2012-01-01

Background Smoking tobacco reduces lung function. African Americans have both lower lung function and decreased metabolism of tobacco smoke compared to European Americans. African ancestry is also associated with lower pulmonary function in African Americans. We aimed to determine whether African ancestry modifies the association between smoking and lung function and its rate of decline in African Americans. Methodology/Principal Findings We evaluated a prospective ongoing cohort of 1,281 African Americans participating in the Health, Aging, and Body Composition (Health ABC) Study initiated in 1997. We also examined an ongoing prospective cohort initiated in 1985 of 1,223 African Americans in the Coronary Artery Disease in Young Adults (CARDIA) Study. Pulmonary function and tobacco smoking exposure were measured at baseline and repeatedly over the follow-up period. Individual genetic ancestry proportions were estimated using ancestry informative markers selected to distinguish European and West African ancestry. African Americans with a high proportion of African ancestry had lower baseline forced expiratory volume in one second (FEV1) per pack-year of smoking (−5.7 ml FEV1/ smoking pack-year) compared with smokers with lower African ancestry (−4.6 ml in FEV1/ smoking pack-year) (interaction P value  = 0.17). Longitudinal analyses revealed a suggestive interaction between smoking, and African ancestry on the rate of FEV1 decline in Health ABC and independently replicated in CARDIA. Conclusions/Significance African American individuals with a high proportion of African ancestry are at greater risk for losing lung function while smoking. PMID:22737244

Considering the effects of ambient particulate matter on the lung function of motorcycle taxi drivers in Bangkok, Thailand.

PubMed

Arphorn, Sara; Ishimaru, Tomohiro; Hara, Kunio; Mahasandana, Suwisa

2018-02-01

The motorcycle taxi drivers of Bangkok have been heavily exposed to high concentrations of PM 10 (particulate matter with an aerodynamic diameter ≤10 μm), and the impact of this on their lungs has been neither documented nor studied. This study examines the association between exposure to PM 10 and lung function decline among motorcycle taxi drivers. A cross-sectional study was conducted in Bangkok between two groups: a subject group of motorcycle taxi drivers and control group of enclosed vehicle taxi drivers. The findings of the Thailand Pollution Control Department were used to estimate the annual ambient PM 10 concentration levels in the metropolis. Pulmonary functions of motorcycle taxi drivers and enclosed vehicle taxi drivers were measured and compared using the Mann-Whitney test. Multiple linear regression analysis was applied to estimate the effects of PM 10 exposure on the lung function of motorcycle taxi drivers. A total of 1283 motorcycle taxi drivers and 600 taxi drivers were investigated. The mean forced expiratory volume in 1 sec/forced vital capacity (FEV 1 /FVC) of the motorcycle taxi drivers was significantly lower than that of the taxi drivers (P < 0.001). The mean FEV 1 /FVC of motorcycle taxi drivers exposed to ≥50 µg/m 3 PM 10 was statistically lower (-2.82%; 95% confidence interval [CI]: -4.54% to -1.09%) and the mean % vital capacity (%VC) of those exposed to 40-49.9 µg/m 3 PM 10 was statistically lower than that of motorcycle taxi drivers exposed to <30 µg/m 3 PM 10 (-3.33%; 95% CI: -5.79% to -0.87%). Motorcycle taxi drivers were directly exposed to air pollution in their working environment. As a result, their lung function might decrease more than that of enclosed vehicle taxi drivers. With the possible exposure to ≥50 µg/m 3 PM 10 , the vehicular emission standards should be vigorously enforced. Further investigation is warranted to clarify the effect of lung dysfunction on the work and lifestyle of motorcycle taxi drivers. Motorcycle taxi drivers are directly exposed to air pollution in their work environment; therefore, their lung function might decrease more than that of enclosed vehicle taxi drivers, especially when exposed to ≥50 µg/m 3 PM 10 . World Health Organization (WHO) vehicular emission standards should be recognized and eventually enforced.

Chronic effects on JP-8 jet fuel exposure on the lungs. Final technical report, 1 April 1991-31 March 1994

DOE Office of Scientific and Technical Information (OSTI.GOV)

Witten, M.L.

1994-06-02

There are four major findings from the three years of work devoted to the effects of chronic JP-8 jet fuel exposure on the lungs and secondary organs. These findings are the following chronic exposure to JP-8 jet fuel alters pulmonary function and lung structures with an acute response with as little as seven days of low dose, approximately 500 mg/m3, exposure to JP-8 jet fuel; chronic exposure to JP-8 jet fuel increased liver, spleen, and kidney weights compared to controls. Microscopic evaluation of liver sections were normal; however, kidney and spleen had histological changes consistent with organic solvent exposure. Theremore » is a correlation between JP-8 jet fuel exposure-induced decreases in lung Substance P levels and lung neutral endopeptidase levels. Chronic exposure to JP-8 jet fuel caused a decrease in lung Substance P levels with a corresponding increase in lung neutral endopeptidase levels; and, there is a recovery process in the 56 day low dose JP-8 jet fuel-exposed lungs as marked by a return to baseline and longitudinal control 99mTcDTPA values. The 99mTcDTPA data was very consistent with our pathologic findings of very little lung injury in the 56 day low dose JP-8 jet fuel-exposed rats. We speculate that this finding indicates that there is a 'threshold' level of JP-8 jet fuel exposure that the lungs' defense mechanism(s) can tolerate.« less

Emodin suppresses silica-induced lung fibrosis by promoting Sirt1 signaling via direct contact.

PubMed

Yang, Tian; Wang, Jinyuan; Pang, Yamei; Dang, Xiaomin; Ren, Hui; Liu, Ya; Chen, Mingwei; Shang, Dong

2016-11-01

Pulmonary silicosis is characterized by lung fibrosis, which leads to impairment of pulmonary function; the specific mechanism remains to be fully elucidated Emodin shows antifibrotic effects in several organs with fibrosis, however, it has not been investigated in pulmonary silicosis. In the present study, the possible mechanism of lung fibrosis and the antifibrotic effect of emodin in silica inhalation‑induced lung fibrosis were investigated. Pulmonary silica particle inhalation was used to induce lung fibrosis in mice. Emodin and or the sirtuin 1 (Sirt1) inhibitor, nicotinamide, were used to treat the modeled animals. Pulmonary function was assessed using an occlusion method. The deposition of collagen I and α‑smooth muscle actin (SMA) in the lung tissue were detected using fluorescence staining; transforming growth factor‑β1 (TGF‑β1) in the bronchoalveolar lavage fluid (BALF) was examined using an enzyme‑linked immunosorbent assay; TGF-β1/Sirt1/small mothers against decapentaplegic (Smad) signaling activation in lung tissue was also examined. The molecular contacts between emodin were evaluated using liquid chromatography‑mass spectrometry analysis. The deposition of collagen I and α‑SMA in lung tissues were found to be elevated following silica exposure, however, this was relieved by emodin treatment. The pulmonary function of the animals was impaired by silica inhalation, and this was improved by emodin administration. However, the therapeutic effects of emodin on lung fibrosis were impaired by nicotinamide administration. The levels of TGF‑β1 in the BALF and lung tissue were elevated by silica inhalation, however, they were not affected by either emodin or nicotinamide treatment. Additionally, emodin was found to increase the expression level of Sirt1, which decreased the level of deacetylated Smad3 to attenuate collagen deposition. Furthermore, the data suggested that there was direct binding between emodin and Sirt1. Sirt1‑regulated TGF‑β1/Smad signaling was involved in silica inhalation‑induced lung fibrosis. Emodin attenuated this lung fibrosis to improve pulmonary function by targeting Sirt1, which regulated TGF-β1/Smad fibrotic signaling.

Emodin suppresses silica-induced lung fibrosis by promoting Sirt1 signaling via direct contact

PubMed Central

Yang, Tian; Wang, Jinyuan; Pang, Yamei; Dang, Xiaomin; Ren, Hui; Liu, Ya; Chen, Mingwei; Shang, Dong

2016-01-01

Pulmonary silicosis is characterized by lung fibrosis, which leads to impairment of pulmonary function; the specific mechanism remains to be fully elucidated Emodin shows antifibrotic effects in several organs with fibrosis, however, it has not been investigated in pulmonary silicosis. In the present study, the possible mechanism of lung fibrosis and the antifibrotic effect of emodin in silica inhalation-induced lung fibrosis were investigated. Pulmonary silica particle inhalation was used to induce lung fibrosis in mice. Emodin and or the sirtuin 1 (Sirt1) inhibitor, nicotinamide, were used to treat the modeled animals. Pulmonary function was assessed using an occlusion method. The deposition of collagen I and α-smooth muscle actin (SMA) in the lung tissue were detected using fluorescence staining; transforming growth factor-β1 (TGF-β1) in the bronchoalveolar lavage fluid (BALF) was examined using an enzyme-linked immunosorbent assay; TGF-β1/Sirt1/small mothers against decapentaplegic (Smad) signaling activation in lung tissue was also examined. The molecular contacts between emodin were evaluated using liquid chromatography-mass spectrometry analysis. The deposition of collagen I and α-SMA in lung tissues were found to be elevated following silica exposure, however, this was relieved by emodin treatment. The pulmonary function of the animals was impaired by silica inhalation, and this was improved by emodin administration. However, the therapeutic effects of emodin on lung fibrosis were impaired by nicotinamide administration. The levels of TGF-β1 in the BALF and lung tissue were elevated by silica inhalation, however, they were not affected by either emodin or nicotinamide treatment. Additionally, emodin was found to increase the expression level of Sirt1, which decreased the level of deacetylated Smad3 to attenuate collagen deposition. Furthermore, the data suggested that there was direct binding between emodin and Sirt1. Sirt1-regulated TGF-β1/Smad signaling was involved in silica inhalation-induced lung fibrosis. Emodin attenuated this lung fibrosis to improve pulmonary function by targeting Sirt1, which regulated TGF-β1/Smad fibrotic signaling. PMID:27748907

Protective effect of grape seed and skin extract against high-fat diet-induced dyshomeostasis of energetic metabolism in rat lung.

PubMed

El Ayed, Mohamed; Kadri, Safwen; Mabrouk, Maha; Aouani, Ezzedine; Elkahoui, Salem

2018-05-10

Obesity is currently one of the major epidemics of this millennium and affects poeples throughout the world. It causes multiple systemic complications as it significantly interferes with respiratory function. We aimed in the present work to study the effect of high fat diet (HFD) on lung oxidative stress and energy metabolism alterations, as well as the putative protection afforded by grape seed and skin extract (GSSE). We started by characterizing the GSSE and its composition using gas chromatography coupled to mass spectrometry (GC-MS). We used a rat model of high-fat-diet and we evaluated the effect of GSSE on oxidative stress and energetic disturbances induced by HFD. We analyzed the effect of HFD on lung oxidative status by assessing lipid oxidation level, non-protein thiols (NPSH) and superoxide anion level… We also evaluated the effect of HFD on creatine kinase (CK), malate dehydrogenase (MDH) and mitochondrial complex IV. HFD induced body weight gain, increased lung weight and lipid content without affecting insulinemia and dropped adiponectemia. HFD also provoked on lung oxidative stress characterized by increased carbonylation (+ 95%; p = 0.0045), decreased of NPSH (- 32%; p = 0.0291) and inhibition of antioxidant enzyme activities such as glutathione peroxidase (- 25%; p = 0.0074). HFD also altered lung intracellular mediators as superoxide anion O 2 ¯ (+ 59%; p = 0.0027) and increased lung xanthine oxidase activity (+ 27%; p = 0.0122). HFD induced copper depletion (- 24%; p = 0.0498) and lead (- 51%: p = 0.0490) from the lung. Correlatively HFD decreased the copper associated enzyme tyrosinase (- 29%; p = 0.0500) and decreased glutamine synthetase activity (- 31%; p = 0.0027). HFD altered also lung energy metabolism by increasing CK activity (+ 22%; p = 0.0108) and decreasing MDH and mitochondrial complex IV activities (- 28%; p = 0.0120, - 31%; p = 0.0086 respectively). Importantly all these alterations were efficiently corrected with GSSE treatment. In conclusion, GSSE has the potential to alleviate the deleterious lipotoxic effect of HFD on lung and it could find potential application in the protection against HFD-induced lung complications.

Idiopathic pulmonary fibrosis may be a disease of recurrent, tractional injury to the periphery of the aging lung: a unifying hypothesis regarding etiology and pathogenesis.

PubMed

Leslie, Kevin O

2012-06-01

Idiopathic pulmonary fibrosis is a progressive, fatal lung disease occurring in older individuals. Despite 50 years of accrued data about the disease, little progress has been made in slowing functional loss or in decreasing patient mortality. To present a novel hypothesis on the etiology and pathogenesis of idiopathic pulmonary fibrosis. Published data are reviewed regarding the epidemiology, clinical presentation, natural history, radiologic findings, and pathologic findings in patients with idiopathic pulmonary fibrosis. Patients with idiopathic pulmonary fibrosis may be predisposed genetically to tractional injury to the peripheral lung. The result is recurrent damage to the epithelial-mesenchymal interface, preferentially at the outer edges of the basilar lung lobules where tractional stress is high during inspiration, compliance is relatively low, and there is a greater tendency for alveolar collapse at end-expiration. A distinctive "reticular network of injury" (the fibroblast focus) forms, attended by a prolonged phase of wound repair (tear and slow repair). Discrete areas of alveolar collapse are observed in scar at the periphery of the lung lobules. The cycle repeats over many years resulting in progressive fibrous remodeling and replacement of the alveoli in a lobule by bronchiolar cysts surrounded by scar (honeycomb lung). Abnormalities in surfactant function are proposed as a potential mechanism of initial lung damage. Age of onset may be a function of a required threshold of environmental exposures (eg, cigarette smoking) or other comorbid injury to the aging lung. Evidence supporting this hypothesis is presented and potential mechanisms are discussed. A potential role for contributing cofactors is presented.

Functional polymorphisms in NFκB1/IκBα predict risks of chronic obstructive pulmonary disease and lung cancer in Chinese.

PubMed

Huang, Dongsheng; Yang, Lei; Liu, Yehua; Zhou, Yumin; Guo, Yuan; Pan, Mingan; Wang, Yunnan; Tan, Yigang; Zhong, Haibo; Hu, Min; Lu, Wenju; Ji, Weidong; Wang, Jian; Ran, Pixin; Zhong, Nanshan; Zhou, Yifeng; Lu, Jiachun

2013-04-01

Lung inflammation is the major pathogenetic feature for both chronic obstructive pulmonary disease (COPD) and lung cancer. The nuclear factor-kappa B (NFκB) and its inhibitor (IκB) play crucial roles in inflammatory. Here, we tested the hypothesis that single nucleotide polymorphisms (SNPs) in NFκB/IκB confer consistent risks for COPD and lung cancer. Four putative functional SNPs (NFκB1: -94del>insATTG; NFκB2: -2966G>A; IκBα: -826C>T, 2758G>A) were analyzed in southern and validated in eastern Chineses to test their associations with COPD risk in 1,511 COPD patients and 1,677 normal lung function controls, as well as lung cancer risk in 1,559 lung cancer cases and 1,679 cancer-free controls. We found that the -94ins ATTG variants (ins/del + ins/ins) in NFκB1 conferred an increased risk of COPD (OR 1.27, 95% CI 1.06-1.52) and promoted COPD progression by accelerating annual FEV1 decline (P = 0.015). The 2758AA variant in IκBα had an increased risk of lung cancer (OR 1.53, 95% CI 1.30-1.80) by decreasing IκBα expression due to the modulation of microRNA hsa-miR-449a but not hsa-miR-34b. Furthermore, both adverse genotypes exerted effect on increasing lung cancer risk in individuals with pre-existing COPD, while the -94del>insATTG did not in those without pre-existing COPD. However, no significant association with COPD or lung cancer was observed for -2966G>A and -826C>T. Our data suggested a common susceptible mechanism of inflammation in lung induced by genetic variants in NFκB1 (-94del>ins ATTG) or IκBα (2758G>A) to predict risk of COPD or lung cancer.

Pre- and postnatal exposure of mice to concentrated urban PM2.5 decreases the number of alveoli and leads to altered lung function at an early stage of life.

PubMed

de Barros Mendes Lopes, Thais; Groth, Espen E; Veras, Mariana; Furuya, Tatiane K; de Souza Xavier Costa, Natalia; Ribeiro Júnior, Gabriel; Lopes, Fernanda Degobbi; de Almeida, Francine M; Cardoso, Wellington V; Saldiva, Paulo Hilario Nascimento; Chammas, Roger; Mauad, Thais

2018-06-04

Gestational exposure to air pollution is associated with negative outcomes in newborns and children. In a previous study, we demonstrated a synergistic negative effect of pre- and postnatal exposure to PM 2.5 on lung development in mice. However, the means by which air pollution affects development of the lung have not yet been identified. In this study, we exposed pregnant BALB/c mice and their offspring to concentrated urban PM 2.5 (from São Paulo, Brazil; target dose 600 μg/m 3 for 1 h daily). Exposure was started on embryonic day 5.5 (E5.5, time of placental implantation). Lung tissue of fetuses and offspring was submitted to stereological and transcriptomic analyses at E14.5 (pseudoglandular stage of lung development), E18.5 (saccular stage) and P40 (postnatal day 40, alveolarized lung). Additionally, lung function and cellularity of bronchoalveolar lavage (BAL) fluid were studied in offspring animals at P40. Compared to control animals that were exposed to filtered air throughout gestation and postnatal life, PM-exposed mice exhibited higher lung elastance and a lower alveolar number at P40 whilst the total lung volume and cellularity of BAL fluid were not affected. Glandular and saccular structures of fetal lungs were not altered upon gestational exposure; transcriptomic signatures, however, showed changes related to DNA damage and its regulation, inflammation and regulation of cell proliferation. A differential expression was validated at E14.5 for the candidates Sox8, Angptl4 and Gas1. Our data substantiate the in utero biomolecular effect of gestational exposure to air pollution and provide first-time stereological evidence that pre- and early life-postnatal exposure compromise lung development, leading to a reduced number of alveoli and an impairment of lung function in the adult mouse. Copyright © 2018 Elsevier Ltd. All rights reserved.

Immune function monitoring in lung transplantation using adenosine triphosphate production: time trends and relationship to postoperative infection.

PubMed

Takahashi, Mamoru; Ohsumi, Akihiro; Ohata, Keiji; Kondo, Takeshi; Motoyama, Hideki; Hijiya, Kyoko; Aoyama, Akihiro; Date, Hiroshi; Chen-Yoshikawa, Toyofumi F

2017-06-01

The ImmuKnow (IK) assay is a comprehensive immune function test that involves measuring adenosine triphosphate produced by the cluster of differentiation 4+ T lymphocytes in peripheral blood. The aim of this study was to analyze the time trends of IK values and assess the relationship between IK values and infections in lung transplants. We prospectively collected 178 blood samples from 22 deceased-donor lung transplant (DDLT) recipients and 17 living-donor lobar lung transplant (LDLLT) recipients. A surveillance IK assay was performed postoperatively, then after 1 week and 1, 3, 6, and 12 months. Time trends of IK values in stable recipients peaked 1 week after DDLT (477 ± 247 ATP ng/ml), and 1 month after LDLLT (433 ± 134 ng/ml), followed by a gradual decline over 1 year. The mean IK values in infections were significantly lower than those in the stable state (119 vs 312 ATP ng/ml, p = 0.0002). IK values increased sharply after lung transplantation and then decreased gradually over time in the first year, suggesting a natural history of immune function. IK values were also significantly reduced during infections. These results may provide new insights into the utility of immune monitoring after lung transplantation.

Air pollution during pregnancy and lung development in the child.

PubMed

Korten, Insa; Ramsey, Kathryn; Latzin, Philipp

2017-01-01

Air pollution exposure has increased extensively in recent years and there is considerable evidence that exposure to particulate matter can lead to adverse respiratory outcomes. The health impacts of exposure to air pollution during the prenatal period is especially concerning as it can impair organogenesis and organ development, which can lead to long-term complications. Exposure to air pollution during pregnancy affects respiratory health in different ways. Lung development might be impaired by air pollution indirectly by causing lower birth weight, premature birth or disturbed development of the immune system. Exposure to air pollution during pregnancy has also been linked to decreased lung function in infancy and childhood, increased respiratory symptoms, and the development of childhood asthma. In addition, impaired lung development contributes to infant mortality. The mechanisms of how prenatal air pollution affects the lungs are not fully understood, but likely involve interplay of environmental and epigenetic effects. The current epidemiological evidence on the effect of air pollution during pregnancy on lung function and children's respiratory health is summarized in this review. While evidence for the adverse effects of prenatal air pollution on lung development and health continue to mount, rigorous actions must be taken to reduce air pollution exposure and thus long-term respiratory morbidity and mortality. Copyright © 2016 Elsevier Ltd. All rights reserved.

Low level laser therapy reduces acute lung inflammation without impairing lung function.

PubMed

Cury, Vivian; de Lima, Thais Martins; Prado, Carla Maximo; Pinheiro, Nathalia; Ariga, Suely K K; Barbeiro, Denise F; Moretti, Ana I; Souza, Heraldo P

2016-12-01

Acute lung injury is a condition characterized by exacerbate inflammatory reaction in distal airways and lung dysfunction. Here we investigate the treatment of acute lung injury (ALI) by low level laser therapy (LLLT), an effective therapy used for the treatment of patients with inflammatory disorders or traumatic injuries, due to its ability to reduce inflammation and promote tissue regeneration. However, studies in internal viscera remains unclear. C57BL/6 mice were treated with intratracheal lipopolysaccharide (LPS) (5 mg/kg) or phosphate buffer saline (PBS). Six hours after instillation, two groups were irradiated with laser at 660 nm and radiant exposure of 10 J/cm 2 . Intratracheal LPS inoculation induced a marked increase in the number of inflammatory cells in perivascular and alveolar spaces. There was also an increase in the expression and secretion of cytokines (TNF-α, IL-1β, IL-6,) and chemokine (MCP-1). The LLLT application induced a significant decrease in both inflammatory cells influx and inflammatory mediators secretion. These effects did not affect lung mechanical properties, since no change was observed in tissue resistance or elastance. In conclusion LLLT is able to reduce inflammatory reaction in lungs exposed to LPS without affecting the pulmonary function and recovery. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Abnormal Pulmonary Function in Adults with Sickle Cell Anemia

PubMed Central

Klings, Elizabeth S.; Wyszynski, Diego F.; Nolan, Vikki G.; Steinberg, Martin H.

2006-01-01

Rationale: Pulmonary complications of sickle cell anemia (Hb-SS) commonly cause morbidity, yet few large studies of pulmonary function tests (PFTs) in this population have been reported. Objectives: PFTs (spirometry, lung volumes, and diffusion capacity for carbon monoxide [DLCO]) from 310 adults with Hb-SS were analyzed to determine the pattern of pulmonary dysfunction and their association with other systemic complications of sickle cell disease. Methods: Raw PFT data were compared with predicted values. Each subject was subclassified into one of five groups: obstructive physiology, restrictive physiology, mixed obstructive/restrictive physiology, isolated low DLCO, or normal. The association between laboratory data of patients with decreased DLCO or restrictive physiology and those of normal subjects was assessed by multivariate linear regression. Measurements and Main Results: Normal PFTs were present in only 31 of 310 (10%) patients. Overall, adults with Hb-SS were characterized by decreased total lung capacities (70.2 ± 14.7% predicted) and DlCO (64.5 ± 19.9%). The most common PFT patterns were restrictive physiology (74%) and isolated low DlCO (13%). Decreased DLCO was associated with thrombocytosis (p = 0.05), with hepatic dysfunction (elevated alanine aminotransferase; p = 0.07), and a trend toward renal dysfunction (elevated blood urea nitrogen and creatinine; p = 0.05 and 0.07, respectively). Conclusions: Pulmonary function is abnormal in 90% of adult patients with Hb-SS. Common abnormalities include restrictive physiology and decreased DLCO. Decreased DLCO may indicate more severe sickle vasculopathy characterized by impaired hepatic and renal function. PMID:16556694

IL-22 Is Essential for Lung Epithelial Repair following Influenza Infection

PubMed Central

Pociask, Derek A.; Scheller, Erich V.; Mandalapu, Sivanarayana; McHugh, Kevin J.; Enelow, Richard I.; Fattman, Cheryl L.; Kolls, Jay K.; Alcorn, John F.

2014-01-01

Influenza infection is widespread in the United States and the world. Despite low mortality rates due to infection, morbidity is common and little is known about the molecular events involved in recovery. Influenza infection results in persistent distal lung remodeling, and the mechanism(s) involved are poorly understood. Recently IL-22 has been found to mediate epithelial repair. We propose that IL-22 is critical for recovery of normal lung function and architecture after influenza infection. Wild-type and IL-22−/− mice were infected with influenza A PR8/34 H1N1 and were followed up for up to 21 days post infection. IL-22 receptor was localized to the airway epithelium in naive mice but was expressed at the sites of parenchymal lung remodeling induced by influenza infection. IL-22−/− mice displayed exacerbated lung injury compared with wild-type mice, which correlated with decreased lung function 21 days post infection. Epithelial metaplasia was observed in wild-type mice but was not evident in IL-22−/− animals that were characterized with an increased fibrotic phenotype. Gene expression analysis revealed aberrant expression of epithelial genes involved in repair processes, among changes in several other biological processes. These data indicate that IL-22 is required for normal lung repair after influenza infection. IL-22 represents a novel pathway involved in interstitial lung disease. PMID:23490254

Effect of exposure to diesel exhaust particles on the susceptibility of the lung to infection.

PubMed

Castranova, V; Ma, J Y; Yang, H M; Antonini, J M; Butterworth, L; Barger, M W; Roberts, J; Ma, J K

2001-08-01

There are at least three mechanisms by which alveolar macrophages play a critical role in protecting the lung from bacterial or viral infections: production of inflammatory cytokines that recruit and activate lung phagocytes, production of antimicrobial reactive oxidant species, and production of interferon (an antiviral agent). In this article we summarize data concerning the effect of exposure to diesel exhaust particles on these alveolar macrophage functions and the role of adsorbed organic chemicals compared to the carbonaceous core in the toxicity of diesel particles. In vitro exposure of rat alveolar macrophages to diesel exhaust particles decreased the ability of lipopolysaccharide (LPS), a bacterial product] to stimulate the production of inflammatory cytokines interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha). Methanol extract exhibited this potential but methanol-washed diesel particles did not. Exposure of rats to diesel exhaust particles by intratracheal instillation also decreased LPS-induced TNF-alpha and IL-1 production from alveolar macrophages. In contrast, carbon black did not exhibit this inhibitory effect. Exposure of rats to diesel exhaust particles by inhalation decreased the ability of alveolar macrophages to produce antimicrobial reactive oxidant species in response to zymosan (a fungal component). In contrast, exposure to coal dust increased zymosan-stimulated oxidant production. In vivo exposure to diesel exhaust particles but not to carbon black decreased the ability of the lungs to clear bacteria. Inhalation exposure of mice to diesel exhaust particles but not to coal dust depressed the ability of the lung to produce the antiviral agent interferon and increased viral multiplication in the lung. These results support the hypothesis that exposure to diesel exhaust particles increases the susceptibility of the lung to infection by depressing the antimicrobial potential of alveolar macrophages. This inhibitory effect appears to be due to adsorbed organic chemicals rather than the carbonaceous core of the diesel particles.

Effect of exposure to diesel exhaust particles on the susceptibility of the lung to infection.

PubMed Central

Castranova, V; Ma, J Y; Yang, H M; Antonini, J M; Butterworth, L; Barger, M W; Roberts, J; Ma, J K

2001-01-01

There are at least three mechanisms by which alveolar macrophages play a critical role in protecting the lung from bacterial or viral infections: production of inflammatory cytokines that recruit and activate lung phagocytes, production of antimicrobial reactive oxidant species, and production of interferon (an antiviral agent). In this article we summarize data concerning the effect of exposure to diesel exhaust particles on these alveolar macrophage functions and the role of adsorbed organic chemicals compared to the carbonaceous core in the toxicity of diesel particles. In vitro exposure of rat alveolar macrophages to diesel exhaust particles decreased the ability of lipopolysaccharide (LPS), a bacterial product] to stimulate the production of inflammatory cytokines interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha). Methanol extract exhibited this potential but methanol-washed diesel particles did not. Exposure of rats to diesel exhaust particles by intratracheal instillation also decreased LPS-induced TNF-alpha and IL-1 production from alveolar macrophages. In contrast, carbon black did not exhibit this inhibitory effect. Exposure of rats to diesel exhaust particles by inhalation decreased the ability of alveolar macrophages to produce antimicrobial reactive oxidant species in response to zymosan (a fungal component). In contrast, exposure to coal dust increased zymosan-stimulated oxidant production. In vivo exposure to diesel exhaust particles but not to carbon black decreased the ability of the lungs to clear bacteria. Inhalation exposure of mice to diesel exhaust particles but not to coal dust depressed the ability of the lung to produce the antiviral agent interferon and increased viral multiplication in the lung. These results support the hypothesis that exposure to diesel exhaust particles increases the susceptibility of the lung to infection by depressing the antimicrobial potential of alveolar macrophages. This inhibitory effect appears to be due to adsorbed organic chemicals rather than the carbonaceous core of the diesel particles. PMID:11544172

Lung matrix and vascular remodeling in mechanically ventilated elastin haploinsufficient newborn mice

PubMed Central

Hilgendorff, Anne; Parai, Kakoli; Ertsey, Robert; Navarro, Edwin; Jain, Noopur; Carandang, Francis; Peterson, Joanna; Mokres, Lucia; Milla, Carlos; Preuss, Stefanie; Alcazar, Miguel Alejandre; Khan, Suleman; Masumi, Juliet; Ferreira-Tojais, Nancy; Mujahid, Sana; Starcher, Barry; Rabinovitch, Marlene

2014-01-01

Elastin plays a pivotal role in lung development. We therefore queried if elastin haploinsufficient newborn mice (Eln+/−) would exhibit abnormal lung structure and function related to modified extracellular matrix (ECM) composition. Because mechanical ventilation (MV) has been linked to dysregulated elastic fiber formation in the newborn lung, we also asked if elastin haploinsufficiency would accentuate lung growth arrest seen after prolonged MV of neonatal mice. We studied 5-day-old wild-type (Eln+/+) and Eln+/− littermates at baseline and after MV with air for 8–24 h. Lungs of unventilated Eln+/− mice contained ∼50% less elastin and ∼100% more collagen-1 and lysyl oxidase compared with Eln+/+ pups. Eln+/− lungs contained fewer capillaries than Eln+/+ lungs, without discernible differences in alveolar structure. In response to MV, lung tropoelastin and elastase activity increased in Eln+/+ neonates, whereas tropoelastin decreased and elastase activity was unchanged in Eln+/− mice. Fibrillin-1 protein increased in lungs of both groups during MV, more in Eln+/− than in Eln+/+ pups. In both groups, MV caused capillary loss, with larger and fewer alveoli compared with unventilated controls. Respiratory system elastance, which was less in unventilated Eln+/− compared with Eln+/+ mice, was similar in both groups after MV. These results suggest that elastin haploinsufficiency adversely impacts pulmonary angiogenesis and that MV dysregulates elastic fiber integrity, with further loss of lung capillaries, lung growth arrest, and impaired respiratory function in both Eln+/+ and Eln+/− mice. Paucity of lung capillaries in Eln+/− newborns might help explain subsequent development of pulmonary hypertension previously reported in adult Eln+/− mice. PMID:25539853

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.

Associations between Ambient Particulate Matter and Nitrogen Dioxide and Chronic Obstructive Pulmonary Diseases in Adults and Effect Modification by Demographic and Lifestyle Factors

PubMed Central

Leem, Jong Han; Kim, Hwan Cheol

2018-01-01

This study was undertaken to investigate the associations between chronic exposure to particulate matter of medium aerodynamic diameter ≤10 or ≤2.5 µm (PM10 or PM2.5) and nitrogen dioxide (NO2) levels and lung function and to examine a possible change in these relationships by demographic and lifestyle factors. Chronic obstructive pulmonary disease (COPD) was defined using the Global Initiative for COPD criteria (forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) of <70%). Associations of lung function and COPD with PM10 or PM2.5 or NO2 were examined using linear and logistic regression analyses among 1264 Korean adults. The highest tertiles of PM2.5 (≥37.1 μg/m3) and NO2 (≥53.8 μg/m3) exposure were significantly associated with COPD (highest versus lowest tertile of PM2.5: adjusted odds ratio (OR) = 1.79, 95% CI: 1.02–3.13; highest versus lowest tertile of NO2: adjusted OR = 1.83, 95% CI: 1.04–3.21). A 10 μg/m3 increase in PM10 concentration was associated with a 1.85 L (95% CI –3.65 to –0.05) decrease in FEV1 and a 1.73 L (95% CI –3.35 to –0.12) decrease in FVC, with the strongest negative association among older people and those with less education. Reduced lung function was associated with PM2.5 exposure in subjects with no physical activity. This study provides evidence that exposure to ambient air pollution has adverse effects on lung function in adults. PMID:29463050

The alpha2-adrenoreceptor agonist dexmedetomidine protects against lipopolysaccharide-induced apoptosis via inhibition of gap junctions in lung fibroblasts.

PubMed

Zhang, Yuan; Tan, Xiaoming; Xue, Lianfang

2018-01-01

The α2-adrenoceptor inducer dexmedetomidine protects against acute lung injury (ALI), but the mechanism of this effect is largely unknown. The present study investigated the effect of dexmedetomidine on apoptosis induced by lipopolysaccharide (LPS) and the relationship between this effect and gap junction intercellular communication in human lung fibroblast cell line. Flow cytometry was used to detect apoptosis induced by LPS. Parachute dye coupling assay was used to measure gap junction function, and western blot analysis was used to determine the expression levels of connexin43 (Cx43). The results revealed that exposure of human lung fibroblast cell line to LPS for 24 h increased the apoptosis, and pretreatment of dexmedetomidine and 18α-GA significantly reduced LPS-induced apoptosis. Dexmedetomidine exposure for 1 h inhibited gap junction function mainly via a decrease in Cx43 protein levels in human lung fibroblast cell line. These results demonstrated that the inhibition of gap junction intercellular communication by dexmedetomidine affected the LPS-induced apoptosis through inhibition of gap junction function by reducing Cx43 protein levels. The present study provides evidence of a novel mechanism underlying the effects of analgesics in counteracting ALI. Copyright © 2017 Elsevier Inc. All rights reserved.

Genome-wide assessment of gene-by-smoking interactions in COPD.

PubMed

Park, Boram; Koo, So-My; An, Jaehoon; Lee, MoonGyu; Kang, Hae Yeon; Qiao, Dandi; Cho, Michael H; Sung, Joohon; Silverman, Edwin K; Yang, Hyeon-Jong; Won, Sungho

2018-06-18

Cigarette smoke exposure is a major risk factor in chronic obstructive pulmonary disease (COPD) and its interactions with genetic variants could affect lung function. However, few gene-smoking interactions have been reported. In this report, we evaluated the effects of gene-smoking interactions on lung function using Korea Associated Resource (KARE) data with the spirometric variables-forced expiratory volume in 1 s (FEV 1 ). We found that variations in FEV 1 were different among smoking status. Thus, we considered a linear mixed model for association analysis under heteroscedasticity according to smoking status. We found a previously identified locus near SOX9 on chromosome 17 to be the most significant based on a joint test of the main and interaction effects of smoking. Smoking interactions were replicated with Gene-Environment of Interaction and phenotype (GENIE), Multi-Ethnic Study of Atherosclerosis-Lung (MESA-Lung), and COPDGene studies. We found that individuals with minor alleles, rs17765644, rs17178251, rs11870732, and rs4793541, tended to have lower FEV 1 values, and lung function decreased much faster with age for smokers. There have been very few reports to replicate a common variant gene-smoking interaction, and our results revealed that statistical models for gene-smoking interaction analyses should be carefully selected.

Factors Affecting Lung Function: A Review of the Literature.

PubMed

Talaminos Barroso, Alejandro; Márquez Martín, Eduardo; Roa Romero, Laura María; Ortega Ruiz, Francisco

2018-06-01

Lung function reference values are traditionally based on anthropometric factors, such as weight, height, sex, and age. FVC and FEV 1 decline with age, while volumes and capacities, such as RV and FRC, increase. TLC, VC, RV, FVC and FEV 1 are affected by height, since they are proportional to body size. This means that a tall individual will experience greater decrease in lung volumes as they get older. Some variables, such as FRC and ERV, decline exponentially with an increase in weight, to the extent that tidal volume in morbidly obese patients can be close to that of RV. Men have longer airways than women, causing greater specific resistance in the respiratory tract. The increased work of breathing to increase ventilation among women means that their consumption of oxygen is higher than men under similar conditions of physical intensity. Lung volumes are higher when the subject is standing than in other positions. DLCO is significantly higher in supine positions than in sitting or standing positions, but the difference between sitting and standing positions is not significant. Anthropometric characteristics are insufficient to explain differences in lung function between different ethnic groups, underlining the importance of considering other factors in addition to the conventional anthropometric measurements. Copyright © 2018 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

Effect of furosemide on pulmonary blood flow distribution in resting and exercising horses

NASA Technical Reports Server (NTRS)

Erickson, H. H.; Bernard, S. L.; Glenny, R. W.; Fedde, M. R.; Polissar, N. L.; Basaraba, R. J.; Walther, S. M.; Gaughan, E. M.; McMurphy, R.; Hlastala, M. P.

1999-01-01

We determined the spatial distribution of pulmonary blood flow (PBF) with 15-micron fluorescent-labeled microspheres during rest and exercise in five Thoroughbred horses before and 4 h after furosemide administration (0.5 mg/kg iv). The primary finding of this study was that PBF redistribution occurred from rest to exercise, both with and without furosemide. However, there was less blood flow to the dorsal portion of the lung during exercise postfurosemide compared with prefurosemide. Furosemide did alter the resting perfusion distribution by increasing the flow to the ventral regions of the lung; however, that increase in flow was abated with exercise. Other findings included 1) unchanged gas exchange and cardiac output during rest and exercise after vs. before furosemide, 2) a decrease in pulmonary arterial pressure after furosemide, 3) an increase in the slope of the relationship of PBF vs. vertical height up the lung during exercise, both with and without furosemide, and 4) a decrease in blood flow to the dorsal region of the lung at rest after furosemide. Pulmonary perfusion variability within the lung may be a function of the anatomy of the pulmonary vessels that results in a predominantly fixed spatial pattern of flow distribution.

Space radiation-associated lung injury in a murine model.

PubMed

Christofidou-Solomidou, Melpo; Pietrofesa, Ralph A; Arguiri, Evguenia; Schweitzer, Kelly S; Berdyshev, Evgeny V; McCarthy, Maureen; Corbitt, Astrid; Alwood, Joshua S; Yu, Yongjia; Globus, Ruth K; Solomides, Charalambos C; Ullrich, Robert L; Petrache, Irina

2015-03-01

Despite considerable progress in identifying health risks to crewmembers related to exposure to galactic/cosmic rays and solar particle events (SPE) during space travel, its long-term effects on the pulmonary system are unknown. We used a murine risk projection model to investigate the impact of exposure to space-relevant radiation (SR) on the lung. C3H mice were exposed to (137)Cs gamma rays, protons (acute, low-dose exposure mimicking the 1972 SPE), 600 MeV/u (56)Fe ions, or 350 MeV/u (28)Si ions at the NASA Space Radiation Laboratory at Brookhaven National Laboratory. Animals were irradiated at the age of 2.5 mo and evaluated 23.5 mo postirradiation, at 26 mo of age. Compared with age-matched nonirradiated mice, SR exposures led to significant air space enlargement and dose-dependent decreased systemic oxygenation levels. These were associated with late mild lung inflammation and prominent cellular injury, with significant oxidative stress and apoptosis (caspase-3 activation) in the lung parenchyma. SR, especially high-energy (56)Fe or (28)Si ions markedly decreased sphingosine-1-phosphate levels and Akt- and p38 MAPK phosphorylation, depleted anti-senescence sirtuin-1 and increased biochemical markers of autophagy. Exposure to SR caused dose-dependent, pronounced late lung pathological sequelae consistent with alveolar simplification and cellular signaling of increased injury and decreased repair. The associated systemic hypoxemia suggested that this previously uncharacterized space radiation-associated lung injury was functionally significant, indicating that further studies are needed to define the risk and to develop appropriate lung-protective countermeasures for manned deep space missions. Copyright © 2015 the American Physiological Society.

Spirometry, Static Lung Volumes, and Diffusing Capacity.

PubMed

Vaz Fragoso, Carlos A; Cain, Hilary C; Casaburi, Richard; Lee, Patty J; Iannone, Lynne; Leo-Summers, Linda S; Van Ness, Peter H

2017-09-01

Spirometric Z-scores from the Global Lung Initiative (GLI) rigorously account for age-related changes in lung function and are thus age-appropriate when establishing spirometric impairments, including a restrictive pattern and air-flow obstruction. However, GLI-defined spirometric impairments have not yet been evaluated regarding associations with static lung volumes (total lung capacity [TLC], functional residual capacity [FRC], and residual volume [RV]) and gas exchange (diffusing capacity). We performed a retrospective review of pulmonary function tests in subjects ≥40 y old (mean age 64.6 y), including pre-bronchodilator measures for: spirometry ( n = 2,586), static lung volumes by helium dilution with inspiratory capacity maneuver ( n = 2,586), and hemoglobin-adjusted single-breath diffusing capacity ( n = 2,508). Using multivariable linear regression, adjusted least-squares means (adj LS Means) were calculated for TLC, FRC, RV, and hemoglobin-adjusted single-breath diffusing capacity. The adj LS Means were expressed with and without height-cubed standardization and stratified by GLI-defined spirometry, including normal ( n = 1,251), restrictive pattern ( n = 663), and air-flow obstruction (mild, [ n = 128]; moderate, [ n = 150]; and severe, [ n = 394]). Relative to normal spirometry, restrictive-pattern had lower adj LS Means for TLC, FRC, RV, and hemoglobin-adjusted single-breath diffusing capacity ( P ≤ .001). Conversely, relative to normal spirometry, mild, moderate, and severe air-flow obstruction had higher adj LS Means for FRC and RV ( P < .001). However, only mild and moderate air-flow obstruction had higher adj LS Means for TLC ( P < .001), while only moderate and severe air-flow obstruction had higher adj LS Means for RV/TLC ( P < .001) and lower adj LS Means for hemoglobin-adjusted single-breath diffusing capacity ( P < .001). Notably, TLC (calculated as FRC + inspiratory capacity) was not increased in severe air-flow obstruction ( P ≥ .11) because inspiratory capacity decreased with increasing air-flow obstruction ( P < .001), thus opposing the increased FRC ( P < .001). Finally, P values were similar whether adj LS Means were height-cubed standardized. A GLI-defined spirometric restrictive pattern is strongly associated with a restrictive ventilatory defect (decreased TLC, FRC, and RV), while GLI-defined spirometric air-flow obstruction is strongly associated with hyperinflation (increased FRC) and air trapping (increased RV and RV/TLC). Both spirometric impairments were strongly associated with impaired gas exchange (decreased hemoglobin-adjusted single-breath diffusing capacity). Copyright © 2017 by Daedalus Enterprises.

Pulmonary FGF-18 gene expression is downregulated during the canalicular-saccular stages in nitrofen-induced hypoplastic lungs.

PubMed

Takahashi, Hiromizu; Friedmacher, Florian; Fujiwara, Naho; Hofmann, Alejandro; Kutasy, Balazs; Gosemann, Jan-Hendrik; Puri, Prem

2013-11-01

Pulmonary hypoplasia (PH) associated with congenital diaphragmatic hernia (CDH) represents one of the major challenges in neonatal intensive care. However, the molecular pathogenesis of PH is still poorly understood. In developing fetal lungs, fibroblast growth factor 18 (FGF-18) plays a crucial role in distal airway maturation. FGF-18 knockouts show smaller lung sizes with reduced alveolar spaces and thicker interstitial mesenchymal compartments, highlighting its important function for fetal lung growth and differentiation. We hypothesized that pulmonary FGF-18 gene expression is downregulated during late gestation in nitrofen-induced hypoplastic lungs. Pregnant rats were exposed to either olive oil or nitrofen on day 9 of gestation (D9). Fetuses were harvested on D18 and D21, and lungs were divided into three groups: controls, hypoplastic lungs without CDH [CDH(-)], and hypoplastic lungs with CDH [CDH(+)] (n = 24 at each time-point). Pulmonary FGF-18 gene expression levels were analyzed by qRT-PCR. Immunohistochemistry was performed to investigate FGF-18 protein expression/distribution. Relative mRNA levels of pulmonary FGF-18 gene expression were significantly decreased in CDH(-) and CDH(+) on D18 and D21 compared to controls (p < 0.05 and p < 0.01, respectively). Immunoreactivity of FGF-18 was markedly diminished in mesenchymal cells surrounding the airway epithelium on D18 and D21 compared to controls. Downregulation of FGF-18 gene expression in nitrofen-induced hypoplastic lungs suggests that decreased FGF-18 expression during the canalicular-saccular stages may interfere with saccular-alveolar differentiation and distal airway maturation resulting in PH.

EYA4 is inactivated biallelically at a high frequency in sporadic lung cancer and is associated with familial lung cancer risk

PubMed Central

Wilson, Ian M.; Vucic, Emily A.; Enfield, Katey S.S.; Thu, Kelsie L.; Zhang, Yu-An; Chari, Raj; Lockwood, William W.; Radulovich, Niki; Starczynowski, Daniel T.; Banáth, Judit P.; Zhang, May; Pusic, Andrea; Fuller, Megan; Lonergan, Kim M.; Rowbotham, David; Yee, John; English, John C.; Buys, Timon P.H.; Selamat, Suhaida A.; Laird-Offringa, Ite A.; Liu, Pengyuan; Anderson, Marshall; You, Ming; Tsao, Ming-Sound; Brown, Carolyn J.; Bennewith, Kevin L.; MacAulay, Calum E.; Karsan, Aly; Gazdar, Adi F.; Lam, Stephen; Lam, Wan L.

2015-01-01

In an effort to identify novel biallelically inactivated tumor suppressor genes (TSG) in sporadic invasive and pre-invasive non-small cell lung cancer (NSCLC) genomes, we applied a comprehensive integrated multi-‘omics approach to investigate patient matched, paired NSCLC tumor and non-malignant parenchymal tissues. By surveying lung tumor genomes for genes concomitantly inactivated within individual tumors by multiple mechanisms, and by the frequency of disruption in tumors across multiple cohorts, we have identified a putative lung cancer TSG, Eyes Absent 4 (EYA4). EYA4 is frequently and concomitantly deleted, hypermethylated and underexpressed in multiple independent lung tumor data sets, in both major NSCLC subtypes, and in the earliest stages of lung cancer. We find not only that decreased EYA4 expression is associated with poor survival in sporadic lung cancers, but EYA4 SNPs are associated with increased familial cancer risk, consistent with EYA4’s proximity to the previously reported lung cancer susceptibility locus on 6q. Functionally, we find that EYA4 displays TSG-like properties with a role in modulating apoptosis and DNA repair. Cross examination of EYA4 expression across multiple tumor types suggests a cell type-specific tumorigenic role for EYA4, consistent with a tumor suppressor function in cancers of epithelial origin. This work shows a clear role for EYA4 as a putative TSG in NSCLC. PMID:24096489

Smoking Cessation in COPD Causes a Transient Improvement in Spirometry and Decreases Micronodules on High-Resolution CT Imaging

PubMed Central

Dhariwal, Jaideep; Tennant, Rachel C.; Hansell, David M.; Westwick, John; Walker, Christoph; Ward, Simon P.; Pride, Neil; Barnes, Peter J.; Kon, Onn Min

2014-01-01

Background: Smoking cessation is of major importance for all smokers; however, in patients with COPD, little information exists on how smoking cessation influences lung function and high-resolution CT (HRCT) scan appearances. Methods: In this single-center study, we performed screening spirometry in a group of heavy smokers aged 40 to 80 years (N = 358). We then studied the effects of smoking cessation in two groups of selected subjects: smokers with COPD (n = 38) and smokers with normal spirometry (n = 55). In parallel to subjects undergoing smoking cessation, we studied a control group of nonsmokers (n = 19). Results: Subjects with COPD who quit smoking had a marked, but transient improvement in FEV1 at 6 weeks (184 mL, n = 17, P < .01) that was still present at 12 weeks (81 mL, n = 17, P < .05) and only partially maintained at 1 year. In contrast, we saw improvement in the transfer factor of lung for carbon monoxide at 6 weeks in both subjects with COPD who quit smoking (0.47 mmol/min/kPa, n = 17, P < .01) and subjects who quit smoking with normal spirometry (0.40 mmol/min/kPa, n = 35, P < .01). An upper-zone single HRCT image slice reliably identified emphysema at baseline in 74% of smokers with COPD (28 of 38) and 29% of healthy smokers (16 of 55). Smoking cessation had no significant effect on the appearances of emphysema but decreased the presence of micronodules on HRCT imaging. Conclusions: Cigarette smoking causes extensive lung function and HRCT image abnormalities, even in patients with normal spirometry. Smoking cessation has differential effects on lung function (FEV1 and gas transfer) and features on HRCT images (emphysema and micronodules). Cessation of smoking in patients with COPD causes a transient improvement in FEV1 and decreases the presence of micronodules, offering an opportunity for concomitant therapy during smoking cessation to augment these effects. Smoking cessation at the earliest possible opportunity is vital to minimize permanent damage to the lungs. PMID:24522562

Open lung approach versus standard protective strategies: Effects on driving pressure and ventilatory efficiency during anesthesia - A pilot, randomized controlled trial.

PubMed

Ferrando, Carlos; Suarez-Sipmann, Fernando; Tusman, Gerardo; León, Irene; Romero, Esther; Gracia, Estefania; Mugarra, Ana; Arocas, Blanca; Pozo, Natividad; Soro, Marina; Belda, Francisco J

2017-01-01

Low tidal volume (VT) during anesthesia minimizes lung injury but may be associated to a decrease in functional lung volume impairing lung mechanics and efficiency. Lung recruitment (RM) can restore lung volume but this may critically depend on the post-RM selected PEEP. This study was a randomized, two parallel arm, open study whose primary outcome was to compare the effects on driving pressure of adding a RM to low-VT ventilation, with or without an individualized post-RM PEEP in patients without known previous lung disease during anesthesia. Consecutive patients scheduled for major abdominal surgery were submitted to low-VT ventilation (6 ml·kg-1) and standard PEEP of 5 cmH2O (pre-RM, n = 36). After 30 min estabilization all patients received a RM and were randomly allocated to either continue with the same PEEP (RM-5 group, n = 18) or to an individualized open-lung PEEP (OL-PEEP) (Open Lung Approach, OLA group, n = 18) defined as the level resulting in maximal Cdyn during a decremental PEEP trial. We compared the effects on driving pressure and lung efficiency measured by volumetric capnography. OL-PEEP was found at 8±2 cmH2O. 36 patients were included in the final analysis. When compared with pre-RM, OLA resulted in a 22% increase in compliance and a 28% decrease in driving pressure when compared to pre-RM. These parameters did not improve in the RM-5. The trend of the DP was significantly different between the OLA and RM-5 groups (p = 0.002). VDalv/VTalv was significantly lower in the OLA group after the RM (p = 0.035). Lung recruitment applied during low-VT ventilation improves driving pressure and lung efficiency only when applied as an open-lung strategy with an individualized PEEP in patients without lung diseases undergoing major abdominal surgery. ClinicalTrials.gov NCT02798133.

The effects of ozone exposure and associated injury mechanisms on the central nervous system.

PubMed

Martínez-Lazcano, Juan Carlos; González-Guevara, Edith; del Carmen Rubio, María; Franco-Pérez, Javier; Custodio, Verónica; Hernández-Cerón, Miguel; Livera, Carlos; Paz, Carlos

2013-01-01

Ozone (O3) is a component of photochemical smog, which is a major air pollutant and demonstrates properties that are harmful to health because of the toxic properties that are inherent to its powerful oxidizing capabilities. Environmental O3 exposure is associated with many symptoms related to respiratory disorders, which include loss of lung function, exacerbation of asthma, airway damage, and lung inflammation. The effects of O3 are not restricted to the respiratory system or function - adverse effects within the central nervous system (CNS) such as decreased cognitive response, decrease in motor activity, headaches, disturbances in the sleep-wake cycle, neuronal dysfunctions, cell degeneration, and neurochemical alterations have also been described; furthermore, it has also been proposed that O3 could have epigenetic effects. O3 exposure induces the reactive chemical species in the lungs, but the short half-life of these chemical species has led some authors to attribute the injurious mechanisms observed within the lungs to inflammatory processes. However, the damage to the CNS induced by O3 exposure is not well understood. In this review, the basic mechanisms of inflammation and activation of the immune system by O3 exposure are described and the potential mechanisms of damage, which include neuroinflammation and oxidative stress, and the signs and symptoms of disturbances within the CNS caused by environmental O3 exposure are discussed.

Identifying decreased diaphragmatic mobility and diaphragm thickening in interstitial lung disease: the utility of ultrasound imaging

PubMed Central

Santana, Pauliane Vieira; Prina, Elena; Albuquerque, André Luis Pereira; Carvalho, Carlos Roberto Ribeiro; Caruso, Pedro

2016-01-01

Objective: To investigate the applicability of ultrasound imaging of the diaphragm in interstitial lung disease (ILD). Methods: Using ultrasound, we compared ILD patients and healthy volunteers (controls) in terms of diaphragmatic mobility during quiet and deep breathing; diaphragm thickness at functional residual capacity (FRC) and at total lung capacity (TLC); and the thickening fraction (TF, proportional diaphragm thickening from FRC to TLC). We also evaluated correlations between diaphragmatic dysfunction and lung function variables. Results: Between the ILD patients (n = 40) and the controls (n = 16), mean diaphragmatic mobility was comparable during quiet breathing, although it was significantly lower in the patients during deep breathing (4.5 ± 1.7 cm vs. 7.6 ± 1.4 cm; p < 0.01). The patients showed greater diaphragm thickness at FRC (p = 0.05), although, due to lower diaphragm thickness at TLC, they also showed a lower TF (p < 0.01). The FVC as a percentage of the predicted value (FVC%) correlated with diaphragmatic mobility (r = 0.73; p < 0.01), and an FVC% cut-off value of < 60% presented high sensitivity (92%) and specificity (81%) for indentifying decreased diaphragmatic mobility. Conclusions: Using ultrasound, we were able to show that diaphragmatic mobility and the TF were lower in ILD patients than in healthy controls, despite the greater diaphragm thickness at FRC in the former. Diaphragmatic mobility correlated with ILD functional severity, and an FVC% cut-off value of < 60% was found to be highly accurate for indentifying diaphragmatic dysfunction on ultrasound. PMID:27167428

ACE and sIL-2R correlate with lung function improvement in sarcoidosis during methotrexate therapy.

PubMed

Vorselaars, Adriane D M; van Moorsel, Coline H M; Zanen, Pieter; Ruven, Henk J T; Claessen, Anke M E; van Velzen-Blad, Heleen; Grutters, Jan C

2015-02-01

In sarcoidosis, the search for disease activity markers that correlate with treatment response is ongoing. The aim of this study was to investigate the pattern of two proposed markers, serum angiotensin-converting enzyme (ACE) and soluble IL-2 receptor (sIL-2R) during methotrexate (MTX) therapy in sarcoidosis patients. We analysed 114 sarcoidosis patients who used MTX for six months, consisting of a subgroup of 76 patients with a pulmonary indication for treatment and a subgroup of 38 patients with an extra-pulmonary indication. ACE and sIL-2R serum levels were measured at baseline and after six months of treatment. Correlation coefficients (R) and odds ratios (ORs) were calculated to study the correlation and predictive effect of serum ACE and sIL-2R levels for pulmonary improvement. High baseline levels of ACE correlated significantly with lung function improvement after treatment (R = 0.45, p < 0.0001; stronger in the pulmonary subgroup R 0.57, p < 0.0001). ACE baseline levels >90 U/l predicted a 10% improvement in overall lung function (OR 3.55; CI 1.34-9.38), with the highest prediction level for 10% improvement in DLCO (OR 4.63; CI 1.23-17.4). After six months of MTX, mean ACE decreased with 17.2 U/l (p < 0.0001) and sIL-2R with 1850 pg/ml (p < 0.0001). Decreases in both ACE and sIL-2R correlated with an increase in lung function. The strongest correlation was found with change in DLCO in the pulmonary subgroup (ACE R = 0.63, P < 0.0001; sIL-2R R = 0.56, P < 0.0001). Baseline and serial serum ACE and sIL-2R levels correlate well with lung function improvement during MTX treatment. Serial measurements of these biomarkers are helpful in monitoring treatment effects in sarcoidosis patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

Analysis of Cell Turnover in the Bronchiolar Epithelium Through the Normal Aging Process.

PubMed

Ortega-Martínez, Marta; Rodríguez-Flores, Laura E; Ancer-Arellano, Adriana; Cerda-Flores, Ricardo M; de-la-Garza-González, Carlos; Ancer-Rodríguez, Jesús; Jaramillo-Rangel, Gilberto

2016-08-01

Aging is associated with changes in the lung that leads to a decrease in its function. Alterations in structure and function in the small airways are well recognized in chronic lung diseases. The aim of this study was the assessment of cell turnover in the bronchiolar epithelium of mouse through the normal aging process. Lungs from CD1 mice at the age of 2, 6, 12, 18, or 24 months were fixed in neutral-buffered formalin and paraffin-embedded. Proliferating cell nuclear antigen was examined by immunohistochemistry. Apoptosis was analyzed by in situ end-labeling of fragmented DNA. Epithelial dimensions were analyzed by morphometry. The 2-month-old mice showed significantly higher number of proliferating cells when compared with mice at all other age groups. The number of apoptotic cells in mice at 24 months of age was significantly greater than in mice at all other age groups. Thus, the number of epithelial cells decreased as the age of the subject increased. We also found reductions in both area and height of the bronchiolar epithelium in mice at 18 and 24 months of age. We found a decrease in the total number of epithelial cells in the aged mice, which was accompanied by a thinning of the epithelium. These changes reflect a dysregulated tissue regeneration process in the bronchiolar epithelium that might predispose to respiratory diseases in elderly subjects.

Red ginseng and vitamin C increase immune cell activity and decrease lung inflammation induced by influenza A virus/H1N1 infection.

PubMed

Kim, Hyemin; Jang, Mirim; Kim, Yejin; Choi, Jiyea; Jeon, Jane; Kim, Jihoon; Hwang, Young-Il; Kang, Jae Seung; Lee, Wang Jae

2016-03-01

Because red ginseng and vitamin C have immunomodulatory function and anti-viral effect, we investigated whether red ginseng and vitamin C synergistically regulate immune cell function and suppress viral infection. Red ginseng and vitamin C were treated to human peripheral blood mononuclear cells (PBMCs) or sarcoma-associated herpesvirus (KSHV)-infected BCBL-1, and administrated to Gulo(-/-) mice, which are incapable of synthesizing vitamin C, with or without influenza A virus/H1N1 infection. Red ginseng and vitamin C increased the expression of CD25 and CD69 of PBMCs and natural killer (NK) cells. Co-treatment of them decreased cell viability and lytic gene expression in BCBL-1. In Gulo(-/-) mice, red ginseng and vitamin C increased the expression of NKp46, a natural cytotoxic receptor of NK cells and interferon (IFN)-γ production. Influenza infection decreased the survival rate, and increased inflammation and viral plaque accumulation in the lungs of vitamin C-depleted Gulo(-/-) mice, which were remarkably reduced by red ginseng and vitamin C supplementation. Administration of red ginseng and vitamin C enhanced the activation of immune cells like T and NK cells, and repressed the progress of viral lytic cycle. It also reduced lung inflammation caused by viral infection, which consequently increased the survival rate. © 2016 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology.

Changes of Arterial Blood Gases After Different Ranges of Surgical Lung Resection

PubMed Central

Cukic, Vesna; Lovre, Vladimir

2012-01-01

Introduction: In recent years there has been increase in the number of patients who need thoracic surgery – first of all different types of pulmonary resection because of primary bronchial cancer, and very often among patients whose lung function is impaired due to different degree of bronchial obstruction so it is necessary to assess functional status before and after lung surgery to avoid the development of respiratory insufficiency. Objective: To show the changes in the level of arterial blood gases after various ranges of lung resection. Material and methods: The study was done on 71 patients surgically treated at the Clinic for Thoracic Surgery KCU Sarajevo, who were previously treated at the Clinic for Pulmonary Diseases “Podhrastovi” in the period from 01. 06. 2009. to 01. 09. 2011. Different types of lung resection were made. Patients whose percentage of ppoFEV1 was (prognosed postoperative FEV1) was less than 30% of normal values of FEV1 for that patients were not given a permission for lung resection. We monitored the changes in levels-partial pressures of blood gases (PaO2, PaCO2 and SaO2) one and two months after resection and compared them to preoperative values. As there were no significant differences between the values obtained one and two months after surgery, in the results we showed arterial blood gas analysis obtained two months after surgical resection. Results were statistically analyzed by SPSS and Microsoft Office Excel. Statistical significance was determined at an interval of 95%. Results: In 59 patients (83%) there was an increase, and in 12 patients (17%) there was a decrease of PaO2, compared to preoperative values. In 58 patients (82%) there was a decrease, and in 13 patients (18%) there was an increase in PaCO2, compared to preoperative values. For all subjects (group as whole): The value of the PaO2 was significantly increased after lung surgery compared to preoperative values (p <0.05) so is the value of the SaO2%. The value of the PaCO2 was significantly decreased after lung surgery compared to preoperative values (p <0.05). Respiratory insufficiency was developed in none of patients. Conclusion: If the % ppoFEV1 (% prognosed postoperative FEV1) is bigger than 30% of normal values of FEV1 (according to sex, weight, height, age) in patient planned for lung resection surgery there is no development of respiratory insufficiency after resection. PMID:23922525

Ethanol intoxication prolongs post-burn pulmonary inflammation: role of alveolar macrophages

PubMed Central

Shults, Jill A.; Curtis, Brenda J.; Boe, Devin M.; Ramirez, Luis; Kovacs, Elizabeth J.

2016-01-01

In this study, the role and fate of AMs were examined in pulmonary inflammation after intoxication and injury. Clinical evidence has revealed that half of all burn patients brought to the emergency department are intoxicated at the time of injury. This combined insult results in amplified neutrophil accumulation and pulmonary edema, with an increased risk of lung failure and mortality, relative to either insult alone. We believe that this excessive pulmonary inflammation, which also parallels decreased lung function, is mediated in part by AMs. Restoration of lung tissue homeostasis is dependent on the eradication of neutrophils and removal of apoptotic cells, both major functions of AMs. Thirty minutes after binge ethanol intoxication, mice were anesthetized and given a 15% total body surface area dorsal scald injury. At 24 h, we found a 50% decrease in the total number of AMs (P < 0.05) and observed a proinflammatory phenotype on the remaining lung AMs. Loss of AMs paralleled a 6-fold increase in the number of TUNEL+ lung apoptotic cells (P < 0.05) and a 3.5-fold increase in the percentage of annexin V+ apoptotic cells in BAL (P < 0.05), after intoxication and injury, relative to controls. In contrast to the reduction in the number of cells, AMs from intoxicated and injured mice had a 4-fold increase in efferocytosis (P < 0.05). In summary, these data suggest that loss of AMs may delay resolution of inflammation, resulting in the pulmonary complications and elevated mortality rates observed in intoxicated and burn-injured patients. PMID:27531926

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sunil, Vasanthi R., E-mail: sunilvr@eohsi.rutgers.edu; Patel, Kinal J., E-mail: kinalv5@gmail.com; Shen, Jianliang, E-mail: jianliangs@gmail.com

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 themore » 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.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sunil, Vasanthi R., E-mail: sunilvr@eohsi.rutgers.edu; Patel-Vayas, Kinal, E-mail: kinalv5@gmail.com; Shen, Jianliang, E-mail: jianliangs@gmail.com

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 oxidemore » 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.« less

Thyroid function in lung cancer

PubMed Central

Ratcliffe, J G; Stack, B H R; Burt, R W; Ratcliffe, W A; Spilg, W G S; Cuthbert, J; Kennedy, R S

1978-01-01

Thyroid function was assessed at the time of initial diagnosis in 204 patients with lung cancer and compared with that of age and sex-matched patients with non-malignant lung disease. Abnormalities in thyroid function were found in 67 patients (33%). The most prevalent abnormality was a low T3 concentration; this was not associated with other clinical or biochemical evidence of hypothyroidism, but the short-term prognosis of these patients was worse than that of matched patients with lung cancer having normal T3 concentrations. Primary hypothyroidism occurred in three patients, low T4 concentrations and free thyroxine index (FTI) with normal thyrotrophin (TSH) concentrations in four patients, and moderately raised TSH with normal thyroid hormone concentrations in six patients; nine patients had a raised FTI with or without raised T4 concentration as the sole abnormality. Overall, the pattern of thyroid hormone metabolism in lung cancer was a tendency towards reduced T3 concentrations with significantly increased T4/T3 ratios and modestly increased 3,3′,5′-triiodothyronine (rT3) concentrations. The altered T4/T3 ratio was particularly noticeable in patients with anaplastic tumours of small (“oat cell”) and large cell types, but was not apparently related to detectable extrathoracic metastases. These data suggest that thyroid hormone metabolism is altered in patients with lung cancer by decreased 5′-monodeiodination of T4. The resulting low T3 concentrations and altered T4/T3 ratio may be partly responsible for the reduced ratio of androsterone to aetiocholanolone observed in lung cancer, which is known to be a poor prognostic sign. PMID:620266

Heavy metals found in the breathing zone, toenails and lung function of welders working in an air-conditioned welding workplace.

PubMed

Hariri, Azian; Mohamad Noor, Noraishah; Paiman, Nuur Azreen; Ahmad Zaidi, Ahmad Mujahid; Zainal Bakri, Siti Farhana

2017-09-22

Welding operations are rarely conducted in an air-conditioned room. However, a company would set its welding operations in an air-conditioned room to maintain the humidity level needed to reduce hydrogen cracks in the specimen being welded. This study intended to assess the exposure to metal elements in the welders' breathing zone and toenail samples. Heavy metal concentration was analysed using inductively coupled plasma mass spectrometry. The lung function test was also conducted and analysed using statistical approaches. Chromium and manganese concentrations in the breathing zone exceeded the permissible exposure limit stipulated by Malaysian regulations. A similar trend was obtained in the concentration of heavy metals in the breathing zone air sampling and in the welders' toenails. Although there was no statistically significant decrease in the lung function of welders, it is suggested that exposure control through engineering and administrative approaches should be considered for workplace safety and health improvement.

Evaluation of respiratory variables in smelter and control workers before and during a shutdown period

DOE Office of Scientific and Technical Information (OSTI.GOV)

Holness, D.L.; Batten, B.; Broder, I.

1985-05-01

Thirty-six smelter workers examined in this pilot study were found to have a higher prevalence of cough and dyspnea and lower baseline lung function than did 31 controls. They also experienced decreases in forced vital capacity (FVC) and forced expiratory volume in 1s (FEV1) over the workweek while the controls did not. Baseline airflow rates and change in FVC and FEV1 over the workweek varied with levels of sulfur dioxide and particulates. Twenty-three smelter workers and 21 controls were seen on a second occasion, six months into an extended shutdown. The smelter workers continued to have a higher prevalence ofmore » cough and dyspnea and lower baseline lung function than the controls. There was, however, a slight increase in lung function in both the exposed workers and the controls during the shutdown. The results suggest that smelter workers may develop both acute and chronic work-related pulmonary effects and that the chronic effects may be nonreversible.« less

The effects of obesity on lung volumes and oxygenation.

PubMed

Littleton, Stephen W; Tulaimat, Aiman

2017-03-01

Obesity can cause hypoxemia by decreasing lung volumes to where there is closure of lung units during normal breathing. Studies describing this phenomenon are difficult to translate into clinical practice. We wanted to determine the lung volume measurements that are associated with hypoxemia in obese patients, and explore how we could use these measurements to identify them. We collected pulmonary function test results and arterial blood gas data on 118 patients without obstruction on pulmonary function testing. We included only patients with normal chest imaging and cardiac testing within one year of the pulmonary function test, to exclude other causes of hypoxemia. We found that as BMI increases, the mean paO 2 , ERV % predicted, and ERV/TLC decrease (BMI 20-30 kg/m 2 : paO 2 =90±8 mmHg, ERV% predicted 112±50, ERV/TLC (%) 19.7±6.5; BMI 30-40 kg/m 2 : paO 2 =84±10 mmHg, ERV% predicted 84±40 ERV/TLC(%) 13.6±7.6; BMI>40 kg/m 2 : paO 2 78 ±12 mmHg, ERV% predicted 64±27 ERV/TLC(%) 11.4±5.8, ANOVA p<0.001). The A-a gradient increases as BMI increases (r=0.42, p<0.001). This correlation was stronger in men (r=0.54) than in women (r=0.35). The paO 2 is lower in patients with a low ERV than in those with a normal ERV (p<0.001). In a multivariate linear regression, only the ERV/TLC predicted (%), age, and BMI were associated with oxygenation (r 2 for A-a gradient =0.28, p=0.036). In obese patients without cardiopulmonary disease, oxygen levels decrease as BMI increases. This effect is associated with the obesity-related reduction in ERV and is independent of hypoventilation. Published by Elsevier Ltd.

No Clinically Significant Changes in Pulmonary Function Following Stereotactic Body Radiation Therapy for Early- Stage Peripheral Non-Small Cell Lung Cancer: An Analysis of RTOG 0236

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stanic, Sinisa, E-mail: sinisa.stanic@carle.com; Paulus, Rebecca; Timmerman, Robert D.

2014-04-01

Purpose: To investigate pulmonary function test (PFT) results and arterial blood gas changes (complete PFT) following stereotactic body radiation therapy (SBRT) and to see whether baseline PFT correlates with lung toxicity and overall survival in medically inoperable patients receiving SBRT for early stage, peripheral, non-small cell lung cancer (NSCLC). Methods and Materials: During the 2-year follow-up, PFT data were collected for patients with T1-T2N0M0 peripheral NSCLC who received effectively 18 Gy × 3 in a phase 2 North American multicenter study (Radiation Therapy Oncology Group [RTOG] protocol 0236). Pulmonary toxicity was graded by using the RTOG SBRT pulmonary toxicity scale. Paired Wilcoxon signedmore » rank test, logistic regression model, and Kaplan-Meier method were used for statistical analysis. Results: At 2 years, mean percentage predicted forced expiratory volume in the first second and diffusing capacity for carbon monoxide declines were 5.8% and 6.3%, respectively, with minimal changes in arterial blood gases and no significant decline in oxygen saturation. Baseline PFT was not predictive of any pulmonary toxicity following SBRT. Whole-lung V5 (the percentage of normal lung tissue receiving 5 Gy), V10, V20, and mean dose to the whole lung were almost identical between patients who developed pneumonitis and patients who were pneumonitis-free. Poor baseline PFT did not predict decreased overall survival. Patients with poor baseline PFT as the reason for medical inoperability had higher median and overall survival rates than patients with normal baseline PFT values but with cardiac morbidity. Conclusions: Poor baseline PFT did not appear to predict pulmonary toxicity or decreased overall survival after SBRT in this medically inoperable population. Poor baseline PFT alone should not be used to exclude patients with early stage lung cancer from treatment with SBRT.« less

[Variations of respiratory parameters in healthy men].

PubMed

Shishkin, G S; Ustiuzhaninova, N V

2006-01-01

The subjects of the study were 656 healthy men living in the south of West Siberia, in whom the basic parameters of gas exchange, lung ventilation, static lung volumes, and bronchial permeability were measured. The significance and incidence of non-pathological changes in the system of external respiration were defined on the basis of statistical and cluster analysis of these parameters. The study shows that individuals with functional changes can be divided into four groups with different characteristics: 1. Steady mobilization of the reserve tissue of the respiratory parts of the lungs as a physiological defense reaction to unfavorable ecological factors; 2. An increased airiness of the respiratory tissue as a sign of a compensatory reaction directed towards maintaining gas homeostasis in frequent and prominent overload of the system of external respiration; 3. Steady hyperventilation as a direct functional response of the organism to the slowing down of oxygen mass transfer in the respiratory parts of the lungs; 4. Restriction of external respiration due to respiratory diseases in the past. Despite differences in the origin, all the studied functional changes have one common feature, i.e. their association with a decrease in external respiratory reserve; all of them should be considered pulmonological risk manifestations.

Effect of Balloon Pulmonary Angioplasty on Respiratory Function in Patients With Chronic Thromboembolic Pulmonary Hypertension.

PubMed

Akizuki, Mina; Serizawa, Naoki; Ueno, Atsuko; Adachi, Taku; Hagiwara, Nobuhisa

2017-03-01

Balloon pulmonary angioplasty (BPA) in chronic thromboembolic pulmonary hypertension (CTEPH) improves hemodynamics and exercise capacity. However, its effect on respiratory function is unclear. Our objective was to investigate the effect of BPA on respiratory function. We enrolled patients with inoperable CTEPH who underwent BPA primarily in lower lobe arteries (first series) and upper and middle lobe arteries (second series). We compared changes in hemodynamics and respiratory function between different BPA fields. Sixty-two BPA sessions were performed in 13 consecutive patients. Mean pulmonary arterial pressure and pulmonary vascular resistance significantly improved from 44 ± 8 to 23 ± 5 mm Hg and 818 ± 383 to 311 ± 117 dyne/s/cm -5 . The percent predicted diffusion capacity of lung for carbon monoxide (Dlco) decreased after BPA in the lower lung field (from 60% ± 8% to 54% ± 8%) with no recovery. Percent Dlco increased after BPA in the upper middle lung field (from 53% ± 6% to 58% ± 6%) and continued to improve during the follow-up (from 58% ± 6% to 64% ± 11%). The ventilation/Co 2 production (V˙e/V˙co 2 ) slope significantly improved after BPA in the lower lung field (from 51 ± 13 to 41 ± 8) and continued to improve during the follow-up (from 41 ± 8 to 35 ± 7); however, the V˙e/V˙co 2 slope remained unchanged after BPA in the upper/middle lung field. Changes in % Dlco and the V˙e/V˙co 2 slope differed significantly between lower and upper/middle lung fields. The effect of BPA on respiratory function in patients with CTEPH differed depending on the lung field. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

75 FR 53907 - Revisions to the Arizona State Implementation Plan, Maricopa County

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-02

... health and the environment, including premature mortality, aggravation of respiratory and cardiovascular disease, decreased lung function, visibility impairment, and damage to vegetation and ecosystems. Section... protection, Air pollution control, Intergovernmental relations, Particulate matter, Reporting and...

Breakdown of lung framework and an increase in pores of Kohn as initial events of emphysema and a cause of reduction in diffusing capacity.

PubMed

Yoshikawa, Akira; Sato, Shuntaro; Tanaka, Tomonori; Hashisako, Mikiko; Kashima, Yukio; Tsuchiya, Tomoshi; Yamasaki, Naoya; Nagayasu, Takeshi; Yamamoto, Hiroshi; Fukuoka, Junya

2016-01-01

Pulmonary emphysema is the pathological prototype of chronic obstructive pulmonary disease and is also associated with other lung diseases. We considered that observation with different approaches may provide new insights for the pathogenesis of emphysema. We reviewed tissue blocks of the lungs of 25 cases with/without emphysema and applied a three-dimensional observation method to the blocks. Based on the three-dimensional characteristics of the alveolar structure, we considered one face of the alveolar polyhedron as a structural unit of alveoli and called it a framework unit (FU). We categorized FUs based on their morphological characteristics and counted their number to evaluate the destructive changes in alveoli. We also evaluated the number and the area of pores of Kohn in FUs. We performed linear regression analysis to estimate the effect of these data on pulmonary function tests. In multivariable regression analysis, a decrease in the number of FUs without an alveolar wall led to a significant decrease in the diffusing capacity of the lung for carbon monoxide (DLCO) and DLCO per unit alveolar volume, and an increase in the area of pores of Kohn had a significant effect on an increase in residual capacity. A breakdown in the lung framework and an increase in pores of Kohn are associated with a decrease in DLCO and DLCO per unit alveolar volume with/without emphysema.

Modeling pressure relationships of inspired air into the human lung bifurcations through simulations

NASA Astrophysics Data System (ADS)

Aghasafari, Parya; Ibrahim, Israr B. M.; Pidaparti, Ramana

2018-03-01

Applied pressure on human lung wall has great importance on setting up protective ventilatory strategies, therefore, estimating pressure relationships in terms of specific parameters would provide invaluable information specifically during mechanical ventilation (MV). A three-dimensional model from a healthy human lung MRI is analyzed by computational fluid dynamic (CFD), and results for pressure are curve fitted to estimate relationships that associate pressure to breathing time, cross section and generation numbers of intended locations. Among all possible functions, it is observed that exponential and polynomial pressure functions present most accurate results for normal breathing (NB) and MV, respectively. For validation, pressure-location curves from CFD and results from this study are compared and good correlations are found. Also, estimated pressure values are used to calculate pressure drop and airway resistance to the induced air into the lung bifurcations. It is concluded that maximum pressure drop appeared in generation number 2 and medium sized airways show higher resistance to air flow and that resistance decreased as cross sectional area increased through the model. Results from this study are in good agreement with previous studies and provide potentials for further studies on influence of air pressure on human lung tissue and reducing lung injuries during MV.

[Lung is also involved in juvenile dermatomyositis].

PubMed

Pouessel, G; Thumerelle, C; Nève, V; Santangelo, T; Flammarion, S; Pruvot, I; Tillie-Leblond, I; Deschildre, A

2014-07-01

Juvenile dermatomyositis is the leading cause of chronic idiopathic inflammatory myopathy of auto-immune origin in children. Lung involvement in inflammatory myopathies is well described in adults, involving mostly interstitial lung disease, aspiration pneumonia and alveolar hypoventilation. We propose to describe its specificities in children. Pulmonary involvement may be asymptomatic and therefore must be systematically screened for. In case of clinical or functional respiratory abnormality, a chest computed tomographic (CT) scan is necessary. In children, a decrease of respiratory muscle strength seems common and should be systematically and specifically searched for by non-invasive and reproducible tests (sniff test). Interstitial lung disease usually associates restrictive functional defect, impairment of carbon monoxide diffusion and interstitial lung disease on CT scan. As in adults, the first-line treatment of juvenile dermatomyositis is based on corticosteroids. Corticosteroid resistant forms require corticosteroid bolus or adjuvant immunosuppressive drugs (methotrexate or cyclosporine). There is no consensus in pediatrics for the treatment of diffuse interstitial lung disease. Complications of treatment, including prolonged steroid therapy, are frequent and therefore a careful assessment of the treatments risk-benefit ratio is necessary, especially in growing children. Copyright © 2014 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

[Amplitude Changes of Low Frequency Fluctuation in Brain Spontaneous Nervous Activities Induced by Needling at Hand Taiyin Lung Channel].

PubMed

Zhou, You-long; Su, Cheng-guo; Liu, Shou-fang; Jin, Xiang-yu; Duan, Yan-li; Chen, Xiao-yan; Zhao, Shu-hua; Wang, Quan-liang; Dang, Chang-lin

2016-05-01

To observe amplitude changes of low frequency fluctuation in brain spontaneous nervous activities induced by needling at Hand Taiyin Lung Channel, and to preliminarily explore the possible brain function network of Hand Taiyin Lung Channel. By using functional magnetic resonance imaging (fMRI), 16 healthy volunteers underwent resting-state scanning (R1) and scanning with retained acupuncture at Hand Taiyin Lung Channel (acupuncture, AP). Data of fMRI collected were statistically calculated using amplitude of low frequency fluctuations (ALFF). Under R1 significantly enhanced ALFF occurred in right precuneus, left inferior parietal lobule, bilateral superior temporal gyrus, bilateral middle frontal gyrus, left superior frontal gyrus, left inferior frontal gyrus, left medial frontal gyrus. Under AP significantly enhanced ALFF occurred in right precuneus, bilateral superior frontal gyrus, cerebellum, bilateral middle frontal gyrus, right medial frontal gyrus, and so on. Compared with R1, needing at Hand Taiyin Lung Channel could significantly enhance ALFF in right gyrus subcallosum and right inferior frontal gyrus. Significant decreased ALFF appeared in right postcentral gyrus, left precuneus, left superior temporal gyrus, left middle temporal gyrus, and so on. Needing at Hand Taiyin Lung Channel could significantly change fixed activities of cerebral cortex, especially in right subcallosal gyrus, right inferior frontal gyrus, and so on.

Ventilatory function in rubber processing workers: acute changes over the workshift.

PubMed Central

Governa, M; Comai, M; Valentino, M; Antonicelli, L; Rinaldi, F; Pisani, E

1987-01-01

When considering rubber tyre manufacturing from an occupational health viewpoint, three areas may be identified in which exposure to respirable materials are potentially harmful: the processing, curing, and talc areas. A study of the ventilatory function of the entire work force employed in the processing area in a rubber tyre manufacturing plant was undertaken to determine whether an acute reduction in lung function occurs over the course of their working shift (the plant worked a three shift system) and whether a chronic exposure to the occupational airborne contaminants causes permanent changes in lung function. The ventilatory function was measured at the worksite at the beginning and immediately after the end of the workshift. No evidence of chronic obstructive pulmonary disease was found and in most cases no significant decline in FEV1 was observed. Only one of the 79 individuals showed a moderate obstruction, measured by the ratio FEV1/FVC which gave the value of 0.55, with no variation over the shift. For non-smokers, the FVC, FEV1, and FEF25-75% were lower in those exposed for more than five years than in those exposed for five years or less. A similar pattern was also observed in the FVC and FEV1 of the smokers. None of these differences was statistically significant. Within each exposure group the pulmonary function of the smokers was lower than that of the non-smokers, but the only significant difference was found in the values of FEF25-75%. Only one man showed a decline in the FEV1/FVC ratio over the shift, but during each shift, a decrease in all the lung function tests was observed. The decrease was smallest during the first of the three shifts. These results are thought to support the hypothesis that there are acute adverse effects over an eight hour shift. Further investigations are needed to discover whether these acute changes in lung function result from a chemical stimulation or irritant receptors in the airways. PMID:3814549

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

PubMed Central

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

2015-01-01

Objectives Hairdressers are exposed to chemicals at the workplace which are known to cause respiratory symptoms and asthma. This study aimed to examine changes in self-reported respiratory symptoms over 5 years, as well as to examine the lung function decline and determine whether it is within the expected range, to assess the dropout rate and reasons for leaving the profession, and to examine the associations between occupational factors and lung function changes at follow-up. Design Prospective study. Setting Female hairdressing salons in Hebron city, Palestine. Participants 170 female hairdressers who participated in a baseline survey in 2008 were followed up in 2013. A total of 161 participants participated in 2013. Outcome measures Change in reported respiratory symptoms and change in lung function over follow-up. Dropout from the profession and reasons for it. Differences between current and former hairdressers in respiratory symptoms and lung function at follow-up. Ambient air ammonia levels in 13 salons. Results Current hairdressers reported more respiratory symptoms in 2013 compared with baseline. Former hairdressers reported fewer symptoms at follow-up. At follow-up, current hairdressers showed a significant decrease in forced vital capacity of 35 mL/year (95% CI 26 to 44 mL/year) and of 31 mL/year (95% CI 25 to 36 mL/year) for forced expiratory volume in 1 s (FEV1). 28 (16%) of the hairdressers quit the job during the 5-year follow-up, 8 (28%) because of health problems. Hairdressers who had been working for 4 years or more at baseline showed a stronger decline in FEV1 compared with those who worked less than 4 years (difference 13, 95% CI 1 to 25). Conclusions Current hairdressers developed more respiratory symptoms and larger lung function decline than former hairdressers during follow-up. Few hairdressers left their profession because of respiratory health problems. Working for more years is associated with lung function decline among current hairdressers. PMID:26474935

Effect on lung function of continuous positive airway pressure administered either by infant flow driver or a single nasal prong.

PubMed

Kavvadia, V; Greenough, A; Dimitriou, G

2000-04-01

The aim of this study was to assess if continuous positive airways pressure (CPAP) delivered by an infant flow driver (IFD) was a more effective method of improving lung function than delivering CPAP by a single nasal prong. A total of 36 infants (median gestational age 29 weeks, range 25-35 weeks) were studied, 12 who received CPAP via an IFD, 12 who received CPAP via a single nasal prong and 12 without CPAP. CPAP was administered post extubation if apnoeas and bradycardias or a respiratory acidosis developed or electively if the infant was of birth weight <1.0 kg. Lung function was assessed by the supplementary oxygen requirement and measurement of compliance of the respiratory system using an occlusion technique. Assessments were made immediately prior to and after 24 h of CPAP administration and at similar postnatal ages in the non-CPAP group. The infants who did not require CPAP had better lung function (non significant) than the other two groups before they received CPAP. After 24 h, lung function had improved in both CPAP groups to the level of the non CPAP infants. The supplementary oxygen requirements of all three groups decreased over the 24 h period, but this only reached significance in the single nasal prong group (P<0.05). Four infants supported by the IFD, but none with a single nasal prong, became hyperoxic. Continuous positive airways pressure administration via the infant flow driver appears to offer no short-term advantage over a single nasal prong system when used after extubation in preterm infants.

Global DNA hypomethylation has no impact on lung function or serum inflammatory and fibrosis cytokines in asbestos-exposed population.

PubMed

Yu, Min; Lou, Jianlin; Xia, Hailing; Zhang, Min; Zhang, Yixiao; Chen, Junqiang; Zhang, Xing; Ying, Shibo; Zhu, Lijin; Liu, Lihong; Jia, Guang

2017-04-01

To examine the effect of asbestos exposure on global DNA methylation and determine whether lung function and inflammatory and fibrosis biomarkers are correlated with the methylation state. A total of 26 healthy subjects without asbestos exposure (Group 1), 47 healthy subjects with exposure (Group 2), and 52 subjects with benign asbestos-related disorders (ARDs) (Group 3) participated in this cross-sectional study. Blood global 5-methylcytosine (5mC) and serum TNF-α, collagen IV, CCL5 and CC16 concentrations were analyzed using enzyme-linked immunosorbent assay-like assays. Spirometric maneuvers were performed to assess lung function. Decreased 5mC levels were observed in Groups 2 and 3 compared to Group 1, irrespective of lung function (p < 0.01). There was no significant change in 5mC between Groups 2 and 3. Overall, 5mC was negatively correlated with CCL5 and collagen IV (p < 0.05), but no significant inverse relationship was found between 5mC and CCL5 or collagen IV in each group. Additionally, both 5mC and CC16 were inversely associated with FEV1/FVC% (p = 0.001, adjusted R 2  = 0.145) for non-smokers, and consistently significant inverse relationships were found between CC16 and FEV1/FVC%, independent of asbestos exposure. Asbestos exposure causes global DNA hypomethylation. DNA hypomethylation has no influence on serum biomarkers and lung function in asbestos-exposed population with or without pleural and pulmonary parenchymal abnormalities.

Function of the Dräger Oxylog ventilator at high altitude.

PubMed

Thomas, G; Brimacombe, J

1994-06-01

We have assessed the performance of the Dräger Oxylog ventilator at high altitude using a decompression chamber and a lung simulator set to mimic the normal and non-compliant lung. In the normal lung, tidal volume increased by 28% at 2040 metres and by 106% at 9120 metres. A lesser change, but in the opposite direction, occurred in respiratory rate. The net effect was a linear increase in minute volume with altitude. At 2040 and 9144 metres minute volume increased by 13% and by 45%, and rate decreased by 10% and 30% respectively. In the abnormal lung stimulation, similar, but slightly less marked, changes occurred in all variables. These changes are of sufficient magnitude to require frequent observation of tidal volume and respiratory rate during aircraft ascent and descent.

Chronic Alcohol Induces M2 Polarization Enhancing Pulmonary Disease Caused by Exposure to Particulate Air Pollution

PubMed Central

Thevenot, Paul; Saravia, Jordy; Giaimo, Joseph; Happel, Kyle I.; Dugas, Tammy R.; Cormier, Stephania A.

2013-01-01

Background Chronic alcohol consumption causes persistent oxidative stress in the lung, leading to impaired alveolar macrophage (AM) function and impaired immune responses. AMs play a critical role in protecting the lung from particulate matter (PM) inhalation by removing particulates from the airway and secreting factors which mediate airway repair. We hypothesized AM dysfunction caused by chronic alcohol consumption increases the severity of injury caused by particulate matter inhalation. Methods Age- and sex-matched C57BL6 mice were fed the Lieber-DeCarli liquid diet containing either alcohol or an iso-caloric substitution (control diet) for 8 weeks. Mice from both diet groups were exposed to combustion derived PM (CDPM) for the final 2 weeks. AM number, maturation, and polarization status were assessed by flow cytometry. Noninvasive and invasive strategies were used to assess pulmonary function and correlated with histomorphological assessments of airway structure and matrix deposition. Results Co-exposure to alcohol and CDPM decreased AM number and maturation status (CD11c expression) while increasing markers of M2 activation (IL-4Rα, Ym1, Fizz1 expression and IL-10 and TGF-β production). Changes in AM function were accompanied by decreased airway compliance and increased elastance. Altered lung function was attributable to elevated collagen content localized to the small airways and loss of alveolar integrity. Intranasal administration of neutralizing antibody to TGF-β during the CDPM exposure period improved changes in airway compliance and elastance while reducing collagen content caused by co-exposure. Conclusion CDPM inhalation causes enhanced disease severity in the alcoholic lung by stimulating the release of latent TGF-β stores in AMs. The combinatorial effect of elevated TGF-β, M2 polarization of AMs, and increased oxidative stress impairs pulmonary function by increasing airway collagen content and compromising alveolar integrity. PMID:23763452

Lung volumes during sustained microgravity on Spacelab SLS-1

NASA Technical Reports Server (NTRS)

Elliott, Ann R.; Prisk, G. Kim; Guy, Harold J. B.; West, John B.

1994-01-01

Gravity is known to influence the mechanical behavior of the lung and chest wall. However, the effect of sustained microgravity (microgravity) on lung volumes has not been reported. Pulmonary function tests were performed by four subjects before, during, and after 9 days of microgravity exposure. Ground measurements were made in standing and supine postures. Tests were performed using a bag-in-box-and-flowmeter system and a respiratory mass spectrometer. Measurements included functional residual capacity (FRC), expiratory reserve volume (ERV), residual volume (RV), inspiratory and expiratory vital capacities (IVC and EVC), and tidal volume (V9sub T)). Total lung capacity (TLC) was derived from the measured EVC and RV values. With preflight standing values as a comparison, FRC was significantly reduced by 15% (approximately 500 ml) in microgravity and 32% in the supine posture. ERV was reduced by 10 - 20% in microgravity and decreased by 64% in the supine posture. RV was significantly reduced by 18% (310 ml) in microgravity but did not significantly change in the supine posture compared with standing. IVC and EVC were slightly reduced during the first 24 h of microgravity but returned to 1-G standing values within 72 h of microgravity exposure. IVC and EVC in the supine posture were significantly reduced by 12% compared with standing. During microgravity, V(sub T) decreased by 15% (approximately 90 ml), but supine V(sub T) was unchanged compared with preflight standing values. TLC decreased by approximately 8% during microgravity and in the supine posture compared with preflight standing. The reductions in FRC, ERV, and RV during microgravity are probably due to the cranial shift of the diaphragm, an increase in intrathoracic blood volume, and more uniform alveolar expansion.

Lung volumes during sustained microgravity on Spacelab SLS-1.

PubMed

Elliott, A R; Prisk, G K; Guy, H J; West, J B

1994-10-01

Gravity is known to influence the mechanical behavior of the lung and chest wall. However, the effect of sustained microgravity (mu G) on lung volumes has not been reported. Pulmonary function tests were performed by four subjects before, during, and after 9 days of mu G exposure. Ground measurements were made in standing and supine postures. Tests were performed using a bag-in-box-and-flowmeter system and a respiratory mass spectrometer. Measurements included functional residual capacity (FRC), expiratory reserve volume (ERV), residual volume (RV), inspiratory and expiratory vital capacities (IVC and EVC), and tidal volume (VT). Total lung capacity (TLC) was derived from the measured EVC and RV values. With preflight standing values as a comparison, FRC was significantly reduced by 15% (approximately 500 ml) in mu G and 32% in the supine posture. ERV was reduced by 10-20% in mu G and decreased by 64% in the supine posture. RV was significantly reduced by 18% (310 ml) in mu G but did not significantly change in the supine posture compared with standing. IVC and EVC were slightly reduced during the first 24 h of mu G but returned to 1-G standing values within 72 h of mu G exposure. IVC and EVC in the supine posture were significantly reduced by 12% compared with standing. During mu G, VT decreased by 15% (approximately 90 ml), but supine VT was unchanged compared with preflight standing values. TLC decreased by approximately 8% during mu G and in the supine posture compared with preflight standing. The reductions in FRC, ERV, and RV during mu G are probably due to the cranial shift of the diaphragm, an increase in intrathoracic blood volume, and more uniform alveolar expansion.

Corticosteroids and fetal intervention interact to alter lung maturation in preterm lambs.

PubMed

Tabor, B L; Lewis, J F; Ikegami, M; Polk, D; Jobe, A H

1994-04-01

The relationship between cortisol infusion and time of fetal catheterization on postnatal lung function of prematurely delivered lambs was investigated with the hypothesis that the intervention of catheterization would alter fetal responsiveness to the maturational effects of corticosteroids. Fetal catheterization was performed on d 117 or on d 122 of gestation. Cortisol or saline control infusions were begun on d 126, with delivery 60 h later on d 128. The animals were ventilated for 1.25 h after delivery, and compliance, the ventilation efficiency index, labeled albumin leak into and out of the lungs, alveolar and lung saturated phosphatidylcholine and surfactant protein A were measured to evaluate lung performance and biochemical indicators of maturation. Cortisol improved compliance and ventilation efficiency and decreased labeled albumin recovery without changing alveolar saturated phosphatidylcholine or surfactant protein A in the animals catheterized at 122 d relative to 122-d saline-infused animals. However, the animals catheterized at 117 d and infused with saline were as mature as assessed by compliance and ventilation efficiency as the 122-d cortisol-treated animals. The 117-d cortisol-infused animals had significantly augmented lung function relative to either 117-d saline-infused or 122-d cortisol-treated lambs and were the only group that had increased alveolar surfactant protein A and lung saturated phosphatidylcholine pool sizes. This study demonstrates that the response of the fetal lung to a maturational agent such as cortisol is dependent on the history of previous fetal interventions.

Employment status and work-related difficulties in lung cancer survivors compared with the general population.

PubMed

Kim, Young Ae; Yun, Young Ho; Chang, Yoon Jung; Lee, Jongmog; Kim, Moon Soo; Lee, Hyun-Sung; Zo, Jae Ill; Kim, Jhingook; Choi, Yong Soo; Shim, Young Mog; Yoon, Seok-Jun

2014-03-01

To investigate the employment status of lung cancer survivors and the work-related problems they face. Although the number of lung cancer survivors is increasing, little is known about their employment and work-related issues. We enrolled 830 lung cancer survivors 12 months after lung cancer curative surgery (median time after diagnosis, 4.11 years) and 1000 volunteers from the general population. All participants completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Core 30-item and a questionnaire that included items relating to their jobs. We used logistic regression analysis to identify independent predictors of unemployment. The employment rate of lung cancer survivors decreased from 68.6% at the time of diagnosis to 38.8% after treatment, which was significantly lower than the employment rate of the general population (63.5%; adjusted odds ratio = 2.31, 95% confidence interval: 1.66-3.22). The posttreatment unemployment rate was higher for women than for men. Among survivors, employment was inversely associated with older age, household income, number of comorbidities, and poor social functioning. Fatigue (78.6%) was the most common work-related problem reported by survivors. Lung cancer survivors experienced more difficulties in employment than did the general population. Age, monthly household income, number of comorbidities, and social functioning appear to be important factors influencing employment status. These findings suggest that lung cancer survivors need support to cope with the financial impact of cancer.

Hypoxic pulmonary vasoconstriction in reptiles: a comparative study of four species with different lung structures and pulmonary blood pressures.

PubMed

Skovgaard, Nini; Abe, Augusto S; Andrade, Denis V; Wang, Tobias

2005-11-01

Low O2 levels in the lungs of birds and mammals cause constriction of the pulmonary vasculature that elevates resistance to pulmonary blood flow and increases pulmonary blood pressure. This hypoxic pulmonary vasoconstriction (HPV) diverts pulmonary blood flow from poorly ventilated and hypoxic areas of the lung to more well-ventilated parts and is considered important for the local matching of ventilation to blood perfusion. In the present study, the effects of acute hypoxia on pulmonary and systemic blood flows and pressures were measured in four species of anesthetized reptiles with diverse lung structures and heart morphologies: varanid lizards (Varanus exanthematicus), caimans (Caiman latirostris), rattlesnakes (Crotalus durissus), and tegu lizards (Tupinambis merianae). As previously shown in turtles, hypoxia causes a reversible constriction of the pulmonary vasculature in varanids and caimans, decreasing pulmonary vascular conductance by 37 and 31%, respectively. These three species possess complex multicameral lungs, and it is likely that HPV would aid to secure ventilation-perfusion homogeneity. There was no HPV in rattlesnakes, which have structurally simple lungs where local ventilation-perfusion inhomogeneities are less likely to occur. However, tegu lizards, which also have simple unicameral lungs, did exhibit HPV, decreasing pulmonary vascular conductance by 32%, albeit at a lower threshold than varanids and caimans (6.2 kPa oxygen in inspired air vs. 8.2 and 13.9 kPa, respectively). Although these observations suggest that HPV is more pronounced in species with complex lungs and functionally divided hearts, it is also clear that other components are involved.

Functional significance and control of release of pulmonary surfactant in the lizard lung.

PubMed

Wood, P G; Daniels, C B; Orgeig, S

1995-10-01

The amount of pulmonary surfactant in the lungs of the bearded dragon (Pogona vitticeps) increases with increasing body temperature. This increase coincides with a decrease in lung compliance. The relationship between surfactant and lung compliance and the principal stimuli for surfactant release and composition (temperature, ventilatory pattern, and autonomic neurotransmitters) were investigated. We chose to investigate ventilatory pattern (which causes mechanical deformation of the type II cells) and adrenergic agents, because they are the major stimuli for surfactant release in mammals. To examine the effects of body temperature and ventilatory pattern, isolated lungs were ventilated at either 18 or 37 degrees C at different ventilatory regimens. An isolated perfused lung preparation at 27 degrees C was used to analyze the effects of autonomic neurotransmitters. Ventilatory pattern did not affect surfactant release, composition, or lung compliance at either 18 or 37 degrees C. An increase in temperature increased phospholipid reuptake and disproportionately increased cholesterol degradation/uptake. Epinephrine and acetylcholine stimulated phospholipid but not cholesterol release. Removal of surfactant caused a decrease in compliance, regardless of the experimental temperature. Temperature appears to be the principal determinant of lung compliance in the bearded dragon, acting directly to increase the tone of the smooth muscle. Increasing the ambient temperature may result in greater surfactant turnover by increasing cholesterol reuptake/degradation directly and by increasing circulating epinephrine, thereby indirectly increasing phospholipid secretion. We suggest that changing ventilatory pattern may be inadequate as a mechanism for maintaining surfactant homeostasis, given the discontinuous, highly variable reptilian breathing pattern.

Impact of geocoding methods on associations between long-term exposure to urban air pollution and lung function.

PubMed

Jacquemin, Bénédicte; Lepeule, Johanna; Boudier, Anne; Arnould, Caroline; Benmerad, Meriem; Chappaz, Claire; Ferran, Joane; Kauffmann, Francine; Morelli, Xavier; Pin, Isabelle; Pison, Christophe; Rios, Isabelle; Temam, Sofia; Künzli, Nino; Slama, Rémy; Siroux, Valérie

2013-09-01

Errors in address geocodes may affect estimates of the effects of air pollution on health. We investigated the impact of four geocoding techniques on the association between urban air pollution estimated with a fine-scale (10 m × 10 m) dispersion model and lung function in adults. We measured forced expiratory volume in 1 sec (FEV1) and forced vital capacity (FVC) in 354 adult residents of Grenoble, France, who were participants in two well-characterized studies, the Epidemiological Study on the Genetics and Environment on Asthma (EGEA) and the European Community Respiratory Health Survey (ECRHS). Home addresses were geocoded using individual building matching as the reference approach and three spatial interpolation approaches. We used a dispersion model to estimate mean PM10 and nitrogen dioxide concentrations at each participant's address during the 12 months preceding their lung function measurements. Associations between exposures and lung function parameters were adjusted for individual confounders and same-day exposure to air pollutants. The geocoding techniques were compared with regard to geographical distances between coordinates, exposure estimates, and associations between the estimated exposures and health effects. Median distances between coordinates estimated using the building matching and the three interpolation techniques were 26.4, 27.9, and 35.6 m. Compared with exposure estimates based on building matching, PM10 concentrations based on the three interpolation techniques tended to be overestimated. When building matching was used to estimate exposures, a one-interquartile range increase in PM10 (3.0 μg/m3) was associated with a 3.72-point decrease in FVC% predicted (95% CI: -0.56, -6.88) and a 3.86-point decrease in FEV1% predicted (95% CI: -0.14, -3.24). The magnitude of associations decreased when other geocoding approaches were used [e.g., for FVC% predicted -2.81 (95% CI: -0.26, -5.35) using NavTEQ, or 2.08 (95% CI -4.63, 0.47, p = 0.11) using Google Maps]. Our findings suggest that the choice of geocoding technique may influence estimated health effects when air pollution exposures are estimated using a fine-scale exposure model.

Role of epithelial-mesenchymal transition (EMT) and fibroblast function in cerium oxide nanoparticles-induced lung fibrosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ma, Jane

The emission of cerium oxide nanoparticles (CeO{sub 2}) from diesel engines, using cerium compounds as a catalyst to lower the diesel exhaust particles, is a health concern. We have previously shown that CeO{sub 2} induced pulmonary inflammation and lung fibrosis. The objective of the present study was to investigate the modification of fibroblast function and the role of epithelial-mesenchymal transition (EMT) in CeO{sub 2}-induced fibrosis. Male Sprague-Dawley rats were exposed to CeO{sub 2} (0.15 to 7 mg/kg) by a single intratracheal instillation and sacrificed at various times post-exposure. The results show that at 28 days after CeO{sub 2} (3.5 mg/kg)more » exposure, lung fibrosis was evidenced by increased soluble collagen in bronchoalveolar lavage fluid, elevated hydroxyproline content in lung tissues, and enhanced sirius red staining for collagen in the lung tissue. Lung fibroblasts and alveolar type II (ATII) cells isolated from CeO{sub 2}-exposed rats at 28 days post-exposure demonstrated decreasing proliferation rate when compare to the controls. CeO{sub 2} exposure was cytotoxic and altered cell function as demonstrated by fibroblast apoptosis and aggregation, and ATII cell hypertrophy and hyperplasia with increased surfactant. The presence of stress fibers, expressed as α-smooth muscle actin (SMA), in CeO{sub 2}-exposed fibroblasts and ATII cells was significantly increased compared to the control. Immunohistofluorescence analysis demonstrated co-localization of TGF-β or α-SMA with prosurfactant protein C (SPC)-stained ATII cells. These results demonstrate that CeO{sub 2} exposure affects fibroblast function and induces EMT in ATII cells that play a role in lung fibrosis. These findings suggest potential adverse health effects in response to CeO{sub 2} nanoparticle exposure. - Highlights: • CeO{sub 2} exposure induced lung fibrosis. • CeO{sub 2} were detected in lung tissue, alveolar type II (ATII) cells and fibroblasts. • CeO{sub 2} caused ATII cell hypertrophy and hyperplasia and altered fibroblast function. • Increased α-SMA in CeO{sub 2}-exposed lung fibroblasts indicating myofibroblast formation. • CeO{sub 2} induced EMT in ATII cells demonstrated as increased α-SMA expression.« less

First-time imaging of effects of inspired oxygen concentration on regional lung volumes and breathing pattern during hypergravity.

PubMed

Borges, João Batista; Hedenstierna, Göran; Bergman, Jakob S; Amato, Marcelo B P; Avenel, Jacques; Montmerle-Borgdorff, Stéphanie

2015-02-01

Aeroatelectasis can develop in aircrew flying the latest generation high-performance aircraft. Causes alleged are relative hyperoxia, increased gravity in the head-to-foot direction (+Gz), and compression of legs and stomach by anti-G trousers (AGT). We aimed to assess, in real time, the effects of hyperoxia, +Gz accelerations and AGT inflation on changes in regional lung volumes and breathing pattern evaluated in an axial plane by electrical impedance tomography (EIT). The protocol mimicked a routine peacetime flight in combat aircraft. Eight subjects wearing AGT were studied in a human centrifuge during 1 h 15 min exposure of +1 to +3.5Gz. They performed this sequence three times, breathing AIR, 44.5 % O2 or 100 % O2. Continuous recording of functional EIT enabled uninterrupted assessment of regional lung volumes at the 5th intercostal level. Breathing pattern was also monitored. EIT data showed that +3.5Gz, compared with any moment without hypergravity, caused an abrupt decrease in regional tidal volume (VT) and regional end-expiratory lung volume (EELV) measured in the EIT slice, independently of inspired oxygen concentration. Breathing AIR or 44.5 % O2, sub-regional EELV measured in the EIT slice decreased similarly in dorsal and ventral regions, but sub-regional VT measured in the EIT slice decreased significantly more dorsally than ventrally. Breathing 100 % O2, EELV and VT decreased similarly in both regions. Inspired tidal volume increased in hyperoxia, whereas breathing frequency increased in hypergravity and hyperoxia. Our findings suggest that hypergravity and AGT inflation cause airway closure and air trapping in gravity-dependent lung regions, facilitating absorption atelectasis formation, in particular during hyperoxia.

Vitamin C supplementation for pregnant smoking women and pulmonary function in their newborn infants: a randomized clinical trial.

PubMed

McEvoy, Cindy T; Schilling, Diane; Clay, Nakia; Jackson, Keith; Go, Mitzi D; Spitale, Patricia; Bunten, Carol; Leiva, Maria; Gonzales, David; Hollister-Smith, Julie; Durand, Manuel; Frei, Balz; Buist, A Sonia; Peters, Dawn; Morris, Cynthia D; Spindel, Eliot R

2014-05-01

Maternal smoking during pregnancy adversely affects offspring lung development, with lifelong decreases in pulmonary function and increased asthma risk. In a primate model, vitamin C blocked some of the in-utero effects of nicotine on lung development and offspring pulmonary function. To determine if newborns of pregnant smokers randomized to receive daily vitamin C would have improved results of pulmonary function tests (PFTs) and decreased wheezing compared with those randomized to placebo. Randomized, double-blind trial conducted in 3 sites in the Pacific Northwest between March 2007 and January 2011. One hundred fifty-nine newborns of randomized pregnant smokers (76 vitamin C treated and 83 placebo treated) and 76 newborns of pregnant nonsmokers were studied with newborn PFTs. Follow-up assessment including wheezing was assessed through age 1 year, and PFTs were performed at age 1 year. Pregnant women were randomized to receive vitamin C (500 mg/d) (n = 89) or placebo (n = 90). The primary outcome was measurement of newborn pulmonary function (ratio of the time to peak tidal expiratory flow to expiratory time [TPTEF:TE] and passive respiratory compliance per kilogram [Crs/kg]) within 72 hours of age. Secondary outcomes included incidence of wheezing through age 1 year and PFT results at age 1 year. A subgroup of pregnant smokers and nonsmokers had genotyping performed. Newborns of women randomized to vitamin C (n = 76), compared with those randomized to placebo (n = 83), had improved pulmonary function as measured by TPTEF:TE (0.383 vs 0.345 [adjusted 95% CI for difference, 0.011-0.062]; P = .006) and Crs/kg (1.32 vs 1.20 mL/cm H2O/kg [95% CI, 0.02-0.20]; P = .01). Offspring of women randomized to vitamin C had significantly decreased wheezing through age 1 year (15/70 [21%] vs 31/77 [40%]; relative risk, 0.56 [95% CI, 0.33-0.95]; P = .03). There were no significant differences in the 1-year PFT results between the vitamin C and placebo groups. The effect of maternal smoking on newborn lung function was associated with maternal genotype for the α5 nicotinic receptor (rs16969968) (P < .001 for interaction). Supplemental vitamin C taken by pregnant smokers improved newborn PFT results and decreased wheezing through 1 year in the offspring. Vitamin C in pregnant smokers may be an inexpensive and simple approach to decrease the effects of smoking in pregnancy on newborn pulmonary function and respiratory morbidities. clinicaltrials.gov Identifier: NCT00632476.

Lung function reductions associated with motor vehicle density in chronic obstructive pulmonary disease: a cross-sectional study.

PubMed

Nitschke, Monika; Appleton, Sarah L; Li, Qiaoyu; Tucker, Graeme R; Shah, Pushan; Bi, Peng; Pisaniello, Dino L; Adams, Robert J

2016-10-24

Motor vehicle-related air pollution can potentially impair lung function. The effect of pollution in people with compromised pulmonary function such as in COPD has not been previously investigated. To examine the association of lung function with motor vehicle density in people with spirometrically determined COPD in a cross-sectional study. In 2004-06, The North West Adelaide Health Study (NWAHS), a biomedical cohort of adults assessed pre and post-bronchodilator spirometry (n = 3,103). Traffic density, obtained from the motor vehicle inventory maintained by the South Australian Environment Protection Authority, was expressed as the daily numbers of vehicles travelling within a 200 m diameter zone around participants' geocoded residences. In subjects with COPD (FEV 1 /FVC <0.7, n = 221, 7.1 %), increasing daily vehicle density was associated with statistically significant decreases in lung function parameters after adjustment for smoking and socio-economic variables. Mean (95 % CI) post-bronchodilator % predicted FEV 1 was 81 % (76-87) in the low (≤7179/day) compared with 71 % (67-75) in the high (≥15,270/day) vehicle exposure group (p < 0.05). Linear regression analysis in all subjects with COPD showed significant decrements in post-bronchodilator FEV 1 /FVC ratio and % predicted FEV 1 of 0.03 and 0.05 % respectively per daily increase in 1000 vehicles. In men with COPD (n = 150), the corresponding reductions were 0.03 and 0.06 %. Smaller, non-significant decrements were seen in females. No difference was seen in those without COPD. Vehicle traffic density was associated with significant reductions in lung function in people with COPD. Urban planning should consider the health impacts for those with pre-existing respiratory conditions.

MicroRNA-218 functions as a tumor suppressor in lung cancer by targeting IL-6/STAT3 and negatively correlates with poor prognosis.

PubMed

Yang, Yan; Ding, Lili; Hu, Qun; Xia, Jia; Sun, Junjie; Wang, Xudong; Xiong, Hua; Gurbani, Deepak; Li, Lianbo; Liu, Yan; Liu, Aiguo

2017-08-22

Aberrant expression of microRNAs in different human cancer types has been widely reported. MiR-218 acts as a tumor suppressor in diverse human cancer types impacting regulation of multiple genes in oncogenic pathways. Here, we evaluated the expression and function of miR-218 in human lung cancer and ALDH positive lung cancer cells to understand the potential mechanisms responsible for disease pathology. Also, the association between its host genes and the target genes could be useful towards the better understanding of prognosis in clinical settings. Publicly-available data from The Cancer Genome Atlas (TCGA) was mined to compare the levels of miR-218 and its host gene SLIT2/3 between lung cancer tissues and normal lung tissues. Transfection of miR-218 to investigate its function in lung cancer cells was done and in vivo effects were determined using miR-218 expressing lentiviruses. Aldefluor assay and Flow cytometry was used to quantify and enrich ALDH positive lung cancer cells. Levels of miR-218, IL-6R, JAK3 and phosphorylated STAT3 were compared in ALDH1A1 positive and ALDH1A1 negative cells. Overexpression of miR-218 in ALDH positive cells was carried to test the survival by tumorsphere culture. Finally, utilizing TCGA data we studied the association of target genes of miR-218 with the prognosis of lung cancer. We observed that the expression of miR-218 was significantly down-regulated in lung cancer tissues compared to normal lung tissues. Overexpression of miR-218 decreased cell proliferation, invasion, colony formation, and tumor sphere formation in vitro and repressed tumor growth in vivo. We further found that miR-218 negatively regulated IL-6 receptor and JAK3 gene expression by directly targeting the 3'-UTR of their mRNAs. In addition, the levels of both miR-218 host genes and the components of IL-6/STAT3 pathway correlated with prognosis of lung cancer patients. MiR-218 acts as a tumor suppressor in lung cancer via IL-6/STAT3 signaling pathway regulation.

Emodin mitigates diesel exhaust particles-induced increase in airway resistance, inflammation and oxidative stress in mice.

PubMed

Nemmar, Abderrahim; Al-Salam, Suhail; Yuvaraju, Priya; Beegam, Sumaya; Ali, Badreldin H

2015-08-15

Clinical and experimental studies have reported that short-term exposure to particulate air pollution is associated with inflammation, oxidative stress and impairment of lung function. Emodin (1,3,8-trihydroxy-6-methylanthraquinone) has a strong antioxidant and anti-inflammatory actions. Therefore, in the present study, we evaluated the possible ameliorative effect of emodin on diesel exhaust particles (DEP)-induced impairment of lung function, inflammation and oxidative stress in mice. Mice were intratracheally instilled with DEP (20 μg/mouse) or saline (control). Emodin was administered intraperitoneally 1h before and 7h after pulmonary exposure to DEP. Twenty-four hours following DEP exposure, we evaluated airway resistance measured by forced oscillation technique, lung inflammation and oxidative stress. Emodin treatment abated the DEP-induced increase in airway resistance, and prevented the influx of neutrophils in bronchoalveolar lavage fluid. Similarly, lung histopathology confirmed the protective effect of emodin on DEP-induced lung inflammation. DEP induced a significant increase of proinflammatory cytokines in the lung including tumor necrosis factor α, interleukin 6 and interleukin 1β. The latter effect was significantly ameliorated by emodin. DEP caused a significant increase in lung lipid peroxidation, reactive oxygen species and a significant decrease of reduced glutathione concentration. These effects were significantly mitigated by emodin. We conclude that emodin significantly mitigated DEP-induced increase of airway resistance, lung inflammation and oxidative stress. Pending further pharmacological and toxicological studies, emodin may be considered a potentially useful pulmonary protective agent against particulate air pollution-induced lung toxicity. Copyright © 2015 Elsevier B.V. All rights reserved.

The D prostanoid receptor agonist BW245C [(4S)-(3-[(3R,S)-3-cyclohexyl-3-hydroxypropyl]-2,5-dioxo)-4-imidazolidineheptanoic acid] inhibits fibroblast proliferation and bleomycin-induced lung fibrosis in mice.

PubMed

van den Brule, Sybille; Wallemme, Laurent; Uwambayinema, Francine; Huaux, François; Lison, Dominique

2010-11-01

Prostaglandin (PG) D(2) exerts contrasting activities in the inflamed lung via two receptors, the D prostanoid receptor (DP) and the chemoattractant receptor-homologous molecule expressed on T helper 2 lymphocytes. DP activation is known mainly to inhibit proinflammatory cell functions. We tested the effect of a DP-specific agonist, (4S)-(3-[(3R,S)-3-cyclohexyl-3-hydroxypropyl]-2,5-dioxo)-4-imidazolidineheptanoic acid (BW245C), on pulmonary fibroblast functions in vitro and in a mouse model of lung fibrosis induced by bleomycin. DP mRNA expression was detected in cultured mouse lung primary fibroblasts and human fetal lung fibroblasts and found to be up- and down-regulated by interleukin-13 and transforming growth factor (TGF)-β, respectively. Although micromolar concentrations of BW245C and PGD(2) did not affect mouse fibroblast collagen synthesis or differentiation in myofibroblasts, they both inhibited fibroblast basal and TGF-β-induced proliferation in vitro. The repeated administration of BW245C (500 nmol/kg body weight instilled transorally in the lungs 2 days before and three times per week for 3 weeks) in bleomycin-treated mice significantly decreased both inflammatory cell recruitment and collagen accumulation in the lung (21 days). Our results indicate that BW245C can reduce lung fibrosis in part via its activity on fibroblast proliferation and suggest that DP activation should be considered as a new therapeutic target in fibroproliferative lung diseases.

Cigarette smoking decreases dynamic inspiratory capacity during maximal exercise in patients with type 2 diabetes.

PubMed

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

2012-06-01

To investigate the influence of cigarette smoking on exercise capacity, respiratory responses and dynamic changes in lung volume during exercise in patients with type 2 diabetes. Forty-one men with type, 2 diabetes without cardiopulmonary disease were recruited and divided into 28 non-current smokers and 13 current smokers. All subjects received lung function tests and cardiopulmonary exercise testing using tracings of the flow-volume loop. Exercise capacity was compared using the percentage of predicted oxygen uptake at maximal workload (%VO2max). Respiratory variables and inspiratory capacity (IC) were compared between the two groups at rest and at 20%, 40%, 60%, 80% and 100% of maximum workload. Although there was no significant difference in lung function tests between the two groups, venous carboxyhemoglobin (CO-Hb) levels were significantly higher in current smokers. %VO2max was inversely correlated with CO-Hb levels. Changing patterns in respiratory rate, respiratory equivalent and IC were significantly different between the two groups. Current smokers had rapid breathing, a greater respiratory equivalent and a limited increase in IC during exercise. Cigarette smoking diminishes the increase in dynamic IC in patients with type 2 diabetes. As this effect of smoking on dynamic changes in lung volume will exacerbate dynamic hyperinflation in cases complicated by chronic obstructive pulmonary disease, physicians should consider smoking habits and lung function when evaluating exercise capacity in patients with type 2 diabetes.

Therapeutic lymphangiogenesis ameliorates established acute lung allograft rejection

PubMed Central

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

2015-01-01

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

Decreased pulmonary c-Cbl expression and tyrosine phosphorylation in the nitrofen-induced rat model of congenital diaphragmatic hernia.

PubMed

Friedmacher, Florian; Gosemann, Jan-Hendrik; Takahashi, Hiromizu; Corcionivoschi, Nicolae; Puri, Prem

2013-01-01

The high morbidity of newborn infants with congenital diaphragmatic hernia (CDH) is attributed to pulmonary hypoplasia (PH), which is characterized by a failure of alveolar development. The nitrofen-induced CDH model has been widely used to investigate the pathogenesis of PH in CDH. It has previously been shown that the fibroblast growth factor receptor (FGFR) pathway, which is essential for a proper lung development, is disrupted during late gestation of nitrofen-induced CDH. Casitas B-lineage lymphoma (c-Cbl) proteins are known regulators of signal transduction through FGFRs, indicating their important role during alveolarization in developing lungs. Furthermore, it has been demonstrated that tyrosine phosphorylation of c-Cbl proteins has a pivotal role for their physiological function and activity during fetal lung development. We designed this study to test the hypothesis that pulmonary c-Cbl expression and tyrosine phosphorylation status are decreased in the nitrofen-induced CDH model. Timed-pregnant rats received either 100 mg nitrofen or vehicle on gestation day 9 (D9). Fetuses were harvested on D18 and D21, and lungs were divided into two groups: control and hypoplastic lungs with CDH (CDH(+)) (n = 10 at each time-point, respectively). Pulmonary gene expression levels of c-Cbl were analyzed by quantitative real-time polymerase chain reaction. Western blotting combined with densitometry analysis was used for semi-quantification of protein levels of pulmonary c-Cbl and tyrosine phosphorylation status. Confocal-immunofluorescence staining was performed to evaluate c-Cbl protein expression and distribution. Relative mRNA expression levels of pulmonary c-Cbl were significantly decreased in CDH(+) on D18 and D21 compared to controls. Western blotting showed markedly decreased protein levels of pulmonary c-Cbl and tyrosine phosphorylation status in CDH(+) on D18 and D21. Confocal-immunofluorescence analysis confirmed decreased c-Cbl expression in CDH(+) on D18 and D21 mainly in the distal alveolar epithelium compared to controls. Decreased pulmonary c-Cbl gene and protein expression accompanied by a decreased tyrosine phosphorylation status during the late stages of fetal lung development may result in reduced c-Cbl activity, and thus interfere with the FGFR-mediated alveolarization in the nitrofen-induced CDH model.

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

Cardiac-related changes in lung resistivity as a function of frequency and location obtained from EITS images.

PubMed

Nopp, P; Zhao, T X; Brown, B H; Wang, W

1996-11-01

ECG-gated electrical impedance tomographic spectroscopy (EITS) measurements of the lungs were taken on seven normal subjects in the frequency range 9.6 kHz to 614.4 kHz. The results show that in late systole the resistivity p' relative to the R-wave (i.e. p' = 1 at the R-wave) decreases consistently within the lung. In addition there arises an increase in p' in early systole towards the periphery of the lung. Frequency behaviour of p' changes with location. At all times after the R-wave, in the centre of the lung p' is higher at higher frequency f whereas in the periphery it is lower at higher f. The principal decrease in p' can be explained by increasing pulmonary blood volume due to cardiac contraction. The early systolic increase is presumably due to venous return to the left atrium locally leading blood output from the right ventricle which is delayed by the windkessel effect. Based on a model taking extracapillary and capillary blood volume increase into account, the change in frequency behaviour of p' is explained by regional variations in extracapillary blood vessel size determining the relative contributions of extracapillary blood volume and capillary blood volume change to p' at a certain frequency.

Childhood pneumonia increases risk for chronic obstructive pulmonary disease: the COPDGene study.

PubMed

Hayden, Lystra P; Hobbs, Brian D; Cohen, Robyn T; Wise, Robert A; Checkley, William; Crapo, James D; Hersh, Craig P

2015-09-21

Development of adult respiratory disease is influenced by events in childhood. The impact of childhood pneumonia on chronic obstructive pulmonary disease (COPD) is not well defined. We hypothesize that childhood pneumonia is a risk factor for reduced lung function and COPD in adult smokers. COPD cases and control smokers between 45-80 years old from the United States COPDGene Study were included. Childhood pneumonia was defined by self-report of pneumonia at <16 years. Subjects with lung disease other than COPD or asthma were excluded. Smokers with and without childhood pneumonia were compared on measures of respiratory disease, lung function, and quantitative analysis of chest CT scans. Of 10,192 adult smokers, 854 (8.4%) reported pneumonia in childhood. Childhood pneumonia was associated with COPD (OR 1.40; 95% CI 1.17-1.66), chronic bronchitis, increased COPD exacerbations, and lower lung function: post-bronchodilator FEV1 (69.1 vs. 77.1% predicted), FVC (82.7 vs. 87.4% predicted), FEV1/FVC ratio (0.63 vs. 0.67; p < 0.001 for all comparisons). Childhood pneumonia was associated with increased airway wall thickness on CT, without significant difference in emphysema. Having both pneumonia and asthma in childhood further increased the risk of developing COPD (OR 1.85; 95% CI 1.10-3.18). Children with pneumonia are at increased risk for future smoking-related lung disease including COPD and decreased lung function. This association is supported by airway changes on chest CT scans. Childhood pneumonia may be an important factor in the early origins of COPD, and the combination of pneumonia and asthma in childhood may pose the greatest risk. ClinicalTrials.gov, NCT00608764 (Active since January 28, 2008).

TU-CD-BRA-11: Application of Bone Suppression Technique to Inspiratory/expiratory Chest Radiography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tanaka, R; Sanada, S; Sakuta, K

Purpose: The bone suppression technique based on advanced image processing can suppress the conspicuity of bones on chest radiographs, creating soft tissue images normally obtained by the dual-energy subtraction technique. This study was performed to investigate the usefulness of bone suppression technique in quantitative analysis of pulmonary function in inspiratory/expiratory chest radiography. Methods: Commercial bone suppression image processing software (ClearRead; Riverain Technologies) was applied to paired inspiratory/expiratory chest radiographs of 107 patients (normal, 33; abnormal, 74) to create corresponding bone suppression images. The abnormal subjects had been diagnosed with pulmonary diseases, such as pneumothorax, pneumonia, emphysema, asthma, and lung cancer.more » After recognition of the lung area, the vectors of respiratory displacement were measured in all local lung areas using a cross-correlation technique. The measured displacement in each area was visualized as displacement color maps. The distribution pattern of respiratory displacement was assessed by comparison with the findings of lung scintigraphy. Results: Respiratory displacement of pulmonary markings (soft tissues) was able to be quantified separately from the rib movements on bone suppression images. The resulting displacement map showed a left-right symmetric distribution increasing from the lung apex to the bottom region of the lung in many cases. However, patients with ventilatory impairments showed a nonuniform distribution caused by decreased displacement of pulmonary markings, which were confirmed to correspond to area with ventilatory impairments found on the lung scintigrams. Conclusion: The bone suppression technique was useful for quantitative analysis of respiratory displacement of pulmonary markings without any interruption of the rib shadows. Abnormal areas could be detected as decreased displacement of pulmonary markings. Inspiratory/expiratory chest radiography combined with the bone suppression technique has potential for predicting local lung function on the basis of dynamic analysis of pulmonary markings. This work was partially supported by Nakatani Foundation, Grant-in-aid for Scientific Research (C) of Ministry of Education, Culture, Sports, Science and Technology, JAPAN (Grant number : 24601007), and Nakatani Foundation, Mitsubishi Foundation, and the he Mitani Foundation for Research and Development. Yasushi Kishitani is a staff of TOYO corporation.« less

Cytochrome c oxidase subunit 4 isoform 2-knockout mice show reduced enzyme activity, airway hyporeactivity, and lung pathology

PubMed Central

Hüttemann, Maik; Lee, Icksoo; Gao, Xiufeng; Pecina, Petr; Pecinova, Alena; Liu, Jenney; Aras, Siddhesh; Sommer, Natascha; Sanderson, Thomas H.; Tost, Monica; Neff, Frauke; Aguilar-Pimentel, Juan Antonio; Becker, Lore; Naton, Beatrix; Rathkolb, Birgit; Rozman, Jan; Favor, Jack; Hans, Wolfgang; Prehn, Cornelia; Puk, Oliver; Schrewe, Anja; Sun, Minxuan; Höfler, Heinz; Adamski, Jerzy; Bekeredjian, Raffi; Graw, Jochen; Adler, Thure; Busch, Dirk H.; Klingenspor, Martin; Klopstock, Thomas; Ollert, Markus; Wolf, Eckhard; Fuchs, Helmut; Gailus-Durner, Valérie; Hrabě de Angelis, Martin; Weissmann, Norbert; Doan, Jeffrey W.; Bassett, David J. P.; Grossman, Lawrence I.

2012-01-01

Cytochrome c oxidase (COX) is the terminal enzyme of the mitochondrial electron transport chain. The purpose of this study was to analyze the function of lung-specific cytochrome c oxidase subunit 4 isoform 2 (COX4i2) in vitro and in COX4i2-knockout mice in vivo. COX was isolated from cow lung and liver as control and functionally analyzed. COX4i2-knockout mice were generated and the effect of the gene knockout was determined, including COX activity, tissue energy levels, noninvasive and invasive lung function, and lung pathology. These studies were complemented by a comprehensive functional screen performed at the German Mouse Clinic (Neuherberg, Germany). We show that isolated cow lung COX containing COX4i2 is about twice as active (88 and 102% increased activity in the presence of allosteric activator ADP and inhibitor ATP, respectively) as liver COX, which lacks COX4i2. In COX4i2-knockout mice, lung COX activity and cellular ATP levels were significantly reduced (−50 and −29%, respectively). Knockout mice showed decreased airway responsiveness (60% reduced Penh and 58% reduced airway resistance upon challenge with 25 and 100 mg methacholine, respectively), and they developed a lung pathology deteriorating with age that included the appearance of Charcot-Leyden crystals. In addition, there was an interesting sex-specific phenotype, in which the knockout females showed reduced lean mass (−12%), reduced total oxygen consumption rate (−8%), improved glucose tolerance, and reduced grip force (−14%) compared to wild-type females. Our data suggest that high activity lung COX is a central determinant of airway function and is required for maximal airway responsiveness and healthy lung function. Since airway constriction requires energy, we propose a model in which reduced tissue ATP levels explain protection from airway hyperresponsiveness, i.e., absence of COX4i2 leads to reduced lung COX activity and ATP levels, which results in impaired airway constriction and thus reduced airway responsiveness; long-term lung pathology develops in the knockout mice due to impairment of energy-costly lung maintenance processes; and therefore, we propose mitochondrial oxidative phosphorylation as a novel target for the treatment of respiratory diseases, such as asthma.—Hüttemann, M., Lee, I., Gao, X., Pecina, P., Pecinova, A., Liu, J., Aras, S., Sommer, N., Sanderson, T. H., Tost, M., Neff, F., Aguilar-Pimentel, J. A., Becker, L., Naton, B., Rathkolb, B., Rozman, J., Favor, J., Hans, W., Prehn, C., Puk, O., Schrewe, A., Sun, M., Höfler, H., Adamski, J., Bekeredjian, R., Graw, J., Adler, T., Busch, D. H., Klingenspor, M., Klopstock, T., Ollert, M., Wolf, E., Fuchs, H., Gailus-Durner, V., Hrabě de Angelis, M., Weissmann, N., Doan, J. W., Bassett, D. J. P., Grossman, L. I. Cytochrome c oxidase subunit 4 isoform 2-knockout mice show reduced enzyme activity, airway hyporeactivity, and lung pathology. PMID:22730437

Adiponectin in Fresh Frozen Plasma Contributes to Restoration of Vascular Barrier Function after Hemorrhagic Shock

PubMed Central

Huby, Maria P.; Duan, Chaojun; Baer, Lisa; Peng, Zhanglong; Kozar, Rosemary A.; Doursout, Marie-Francoise; Holcomb, John B.; Wade, Charles E.; Ko, Tien C.

2015-01-01

Hemorrhagic shock is the leading cause of preventable deaths in civilian and military trauma. Use of fresh frozen plasma (FFP) in patients requiring massive transfusion is associated with improved outcomes. FFP contains significant amounts of adiponectin, which is known to have vascular protective function. We hypothesize that FFP improves vascular barrier function largely via adiponectin. Plasma adiponectin levels were measured in 19 severely injured patients in hemorrhagic shock (HS). Compared to normal individuals, plasma adiponectin levels decreased to 49% in HS patients prior to resuscitation (p<0.05) and increased to 64% post resuscitation (but not significant). In a HS mouse model, we demonstrated a similar decrease in plasma adiponectin to 54% but a significant increase to 79% by FFP resuscitation compared to baseline (p<0.05). HS disrupted lung vascular barrier function, leading to an increase in permeability. FFP resuscitation reversed these HS-induced effects. Immunodepletion of adiponectin from FFP abolished FFP's effects on blocking endothelial hyperpermeability in vitro, and on improving lung vascular barrier function in HS mice. Replenishment with adiponectin rescued FFP's effects. These findings suggest that adiponectin is an important component in FFP resuscitation contributing to the beneficial effects on vascular barrier function after HS. PMID:26263440

Daily propranolol prevents prolonged mobilization of hematopoietic progenitor cells in a rat model of lung contusion, hemorrhagic shock, and chronic stress.

PubMed

Bible, Letitia E; Pasupuleti, Latha V; Gore, Amy V; Sifri, Ziad C; Kannan, Kolenkode B; Mohr, Alicia M

2015-09-01

Propranolol has been shown previously to decrease the mobilization of hematopoietic progenitor cells (HPCs) after acute injury in rodent models; however, this acute injury model does not reflect the prolonged period of critical illness after severe trauma. Using our novel lung contusion/hemorrhagic shock/chronic restraint stress model, we hypothesize that daily administration of propranolol will decrease prolonged mobilization of HPCs without worsening lung healing. Male Sprague-Dawley rats underwent 6 days of restraint stress after undergoing lung contusion or lung contusion/hemorrhagic shock. Restraint stress consisted of a daily 2-hour period of restraint interrupted every 30 minutes by alarms and repositioning. Each day after the period of restraint stress, the rats received intraperitoneal propranolol (10 mg/kg). On day 7, peripheral blood was analyzed for granulocyte-colony stimulating factor (G-CSF) and stromal cell-derived factor 1 via enzyme-linked immunosorbent assay and for mobilization of HPCs using c-kit and CD71 flow cytometry. The lungs were examined histologically to grade injury. Seven days after lung contusion and lung contusion/hemorrhagic shock, the addition of chronic restraint stress significantly increased the mobilization of HPC, which was associated with persistently increased levels of G-CSF and increased lung injury scores. The addition of propranolol to lung contusion/chronic restraint stress and lung contusion/hemorrhagic shock/chronic restraint stress models greatly decreased HPC mobilization and restored G-CSF levels to that of naïve animals without worsening lung injury scores. The daily administration of propranolol after both lung contusion and lung contusion/hemorrhagic shock subjected to chronic restraint stress decreased the prolonged mobilization of HPC from the bone marrow and decreased plasma G-CSF levels. Despite the decrease in mobilization of HPC, lung healing did not worsen. Alleviating chronic stress with propranolol may be a future therapeutic target to improve healing after severe injury. Copyright © 2015 Elsevier Inc. All rights reserved.

WE-AB-202-03: Quantifying Ventilation Change Due to Radiation Therapy Using 4DCT Jacobian Calculations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Patton, T; Du, K; Bayouth, J

Purpose: Four-dimensional computed tomography (4DCT) and image registration can be used to determine regional lung ventilation changes after radiation therapy (RT). This study aimed to determine if lung ventilation change following radiation therapy was affected by the pre-RT ventilation of the lung. Methods: 13 subjects had three 4DCT scans: two repeat scans acquired before RT and one three months after RT. Regional ventilation was computed using Jacobian determinant calculations on the registered 4DCT images. The post-RT ventilation map was divided by the pre-RT ventilation map to get a voxel-by-voxel Jacobian ratio map depicting ventilation change over the course of RT.more » Jacobian ratio change was compared over the range of delivered doses. The first pre-RT ventilation image was divided by the second to establish a control for Jacobian ratio change without radiation delivered. The functional change between scans was assessed using histograms of the Jacobian ratios. Results: There were significantly (p < 0.05) more voxels that had a large decrease in Jacobian ratio in the post-RT divided by pre-RT map (15.6%) than the control (13.2%). There were also significantly (p < .01) more voxels that had a large increase in Jacobian ratio (16.2%) when compared to control (13.3%). Lung regions with low function (<10% expansion by Jacobian) showed a slight linear reduction in expansion (0.2%/10 Gy delivered), while high function regions (>10% expansion) showed a greater response (1.2% reduction/10 Gy). Contiguous high function regions > 1 liter occurred in 11 of 13 subjects. Conclusion: There is a significant change in regional ventilation following a course of radiation therapy. The change in Jacobian following RT is dependent both on the delivered dose and the initial ventilation of the lung tissue: high functioning lung has greater ventilation loss for equivalent radiation doses. Substantial regions of high function lung tissue are prevalent. Research support from NIH grants CA166119 and CA166703, a gift from Roger Koch, and a Pilot Grant from University of Iowa Carver College of Medicine.« less

Effect on lung function of mounthpiece ventilation in Steinert disease. A case report.

PubMed

Annunziata, Anna; Fiorentino, Giuseppe; Esquinas, Antonio

2017-03-01

In patients with muscular dystrophies both muscle length tension relationship changes and muscle elasticity and plasticity are decreased, resulting in impaired inspiratory muscle function and decreased vital capacity. Furthermore, the loss of deep breathing further increases the risk of alveolar collapse, hypoventilation and atelectasias. In this case report, a stable improvement of vital capacity after treatment with mounthpiece ventilation (MPV), was observed, suggesting that not invasive ventilation (NIV) might help to maintai lung and chest wall compliance, prevent hypoventilation and atelectasias which in turn may slow down the development of the restrictive respiratory pattern. The improvement of vital capacity may have a positive impact on alveolar ventilation by reducing the time with SaO2 values below 90%. This case illustrates that MPV is an effective method to improve respiratory function in patients non-tolerant of nasal mask and a valid alternative option for those who need NIV support for the most part of the day. Furthermore, the use of MPV, alone or combined with other interfaces, improves the quality of life of the neuromuscular patients and promotes a greater adherence to mechanical ventilation.

Stochastic dosimetry model for radon progeny in the rat lung.

PubMed

Winkler-HeiI, R; Hofmann, W; Hussain, M

2014-07-01

The stochastic dosimetry model presented here considers the distinctly asymmetric, stochastic branching pattern reported in morphometric measurements. This monopodial structure suggests that an airway diameter is a more appropriate morphometric parameter to classify bronchial dose distributions for inhaled radon progeny than the commonly assigned airway generation numbers. Bronchial doses were calculated for the typical exposure conditions reported for the Pacific Northwest National Laboratory rat inhalation studies, yielding an average bronchial dose of 7.75 mGy WLM(-1). If plotted as functions of airway generations, the resulting dose distributions are highest in the central bronchial airways, while significantly decreasing towards peripheral generations. However, if plotted as functions of airway diameters, doses are much more uniformly distributed among bronchial airways. The comparison between rat and human lungs indicates that dose conversion coefficients for the rat lung are higher than the corresponding values for the human lung by a factor of 1.34 for the experimental PNNL exposure conditions, and of 1.25 for typical human indoor conditions. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

[Sputum viscosity and pulmonary function measurements during a one-week parenteral treatment with a standardized oxidation product of oil of turpentine and terpin hydrate].

PubMed

Löllgen-Horres, I; Löllgen, H

1976-01-01

In 23 patients with chronic obstructive lung diseases, viscosity, airway resistance, arterial blood gases and acid-base balance, and sputum aspect were measured before and after one-week treatment with Ozothin, a substance from oxidation products of ol. terebinth. and terpinum hydratum. Within this time, viscosity of the sputum was reduced, airway resistance decreased, and arterial oxygen pressure slightly increased, whereas arterial carbon dioxide tension obvious change of sputum aspect could be observed. Correlation calculations revealed no significant relations between viscosity and the above cited lung function values. The results indicate that administration of Ozothin may liquefy viscous secretion and reduce sputum viscosity.

Occupational Lung Disease Risk and Exposure to Butter-Flavoring Chemicals After Implementation of Controls at a Microwave Popcorn Plant

PubMed Central

Kanwal, Richard; Kullman, Greg; Fedan, Kathleen B.; Kreiss, Kathleen

2011-01-01

Objectives After an outbreak of severe lung disease among workers exposed to butter-flavoring chemicals at a microwave popcorn plant, we determined whether or not lung disease risk declined after implementation of exposure controls. Methods National Institute for Occupational Safety and Health staff performed eight serial cross-sectional medical and industrial hygiene surveys at the plant from November 2000 through August 2003. Medical surveys included standardized questionnaires and spirometry testing. Industrial hygiene surveys measured levels of production-related air contaminants, including butter-flavoring chemicals such as diacetyl. All diacetyl concentrations above detectable limits were corrected for the effects of absolute humidity and days to sample extraction. Results Ventilation and isolation of the production process resulted in one to three orders of magnitude reductions in diacetyl air concentrations in different areas of the plant. Workers with past high exposures had stable chest symptoms over time; nasal, eye, and skin irritation symptoms declined. New workers had lower symptom prevalences and higher lung function than workers with past high exposures, and they did not worsen over time. In workers who had at least three spirometry tests, those with past high exposures were more likely to experience rapid declines in lung function than new workers. Conclusions Implemented controls lowered exposures to butter-flavoring chemicals and decreased lung disease risk for much of the plant workforce. Some workers with continuing potential for intermittent, short-term peak and measurable time-weighted exposures remain at risk and should use respiratory protection and have regularly scheduled spirometry to detect rapid lung function declines that may be work-related. Close follow-up of such workers is likely to yield additional information on risks due to peak and time-weighted exposure levels. PMID:21800743

Occupational lung disease risk and exposure to butter-flavoring chemicals after implementation of controls at a microwave popcorn plant.

PubMed

Kanwal, Richard; Kullman, Greg; Fedan, Kathleen B; Kreiss, Kathleen

2011-01-01

After an outbreak of severe lung disease among workers exposed to butter-flavoring chemicals at a microwave popcorn plant, we determined whether or not lung disease risk declined after implementation of exposure controls. National Institute for Occupational Safety and Health staff performed eight serial cross-sectional medical and industrial hygiene surveys at the plant from November 2000 through August 2003. Medical surveys included standardized questionnaires and spirometry testing. Industrial hygiene surveys measured levels of production-related air contaminants, including butter-flavoring chemicals such as diacetyl. All diacetyl concentrations above detectable limits were corrected for the effects of absolute humidity and days to sample extraction. Ventilation and isolation of the production process resulted in one to three orders of magnitude reductions in diacetyl air concentrations in different areas of the plant. Workers with past high exposures had stable chest symptoms over time; nasal, eye, and skin irritation symptoms declined. New workers had lower symptom prevalences and higher lung function than workers with past high exposures, and they did not worsen over time. In workers who had at least three spirometry tests, those with past high exposures were more likely to experience rapid declines in lung function than new workers. Implemented controls lowered exposures to butter-flavoring chemicals and decreased lung disease risk for much of the plant workforce. Some workers with continuing potential for intermittent, short-term peak and measurable time-weighted exposures remain at risk and should use respiratory protection and have regularly scheduled spirometry to detect rapid lung function declines that may be work-related. Close follow-up of such workers is likely to yield additional information on risks due to peak and time-weighted exposure levels.

Effect of phrenic nerve palsy on early postoperative lung function after pneumonectomy: a prospective study.

PubMed

Kocher, Gregor J; Mauss, Karl; Carboni, Giovanni L; Hoksch, Beatrix; Kuster, Roland; Ott, Sebastian R; Schmid, Ralph A

2013-12-01

The issue of phrenic nerve preservation during pneumonectomy is still an unanswered question. So far, its direct effect on immediate postoperative pulmonary lung function has never been evaluated in a prospective trial. We conducted a prospective crossover study including 10 patients undergoing pneumonectomy for lung cancer between July 2011 and July 2012. After written informed consent, all consecutive patients who agreed to take part in the study and in whom preservation of the phrenic nerve during operation was possible, were included in the study. Upon completion of lung resection, a catheter was placed in the proximal paraphrenic tissue on the pericardial surface. After an initial phase of recovery of 5 days all patients underwent ultrasonographic assessment of diaphragmatic motion followed by lung function testing with and without induced phrenic nerve palsy. The controlled, temporary paralysis of the ipsilateral hemidiaphragm was achieved by local administration of lidocaine 1% at a rate of 3 mL/h (30 mg/h) via the above-mentioned catheter. Temporary phrenic nerve palsy was accomplished in all but 1 patient with suspected catheter dislocation. Spirometry showed a significant decrease in dynamic lung volumes (forced expiratory volume in 1 second and forced vital capacity; p < 0.05) with the paralyzed hemidiaphragm. Blood oxygen saturation levels did not change significantly. Our results show that phrenic nerve palsy causes a significant impairment of dynamic lung volumes during the early postoperative period after pneumonectomy. Therefore, in these already compromised patients, intraoperative phrenic nerve injury should be avoided whenever possible. Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Assessing exposure risk for dust storm events-associated lung function decrement in asthmatics and implications for control

NASA Astrophysics Data System (ADS)

Hsieh, Nan-Hung; Liao, Chung-Min

2013-04-01

Asian dust storms (ADS) events are seasonally-based meteorological phenomena that exacerbate chronic respiratory diseases. The purpose of this study was to assess human health risk from airborne dust exposure during ADS events in Taiwan. A probabilistic risk assessment framework was developed based on exposure and experimental data to quantify ADS events induced lung function decrement. The study reanalyzed experimental data from aerosol challenge in asthmatic individuals to construct the dose-response relationship between inhaled dust aerosol dose and decreasing percentage of forced expiratory volume in 1 s (%FEV1). An empirical lung deposition model was used to predict deposition fraction for size specific dust aerosols in pulmonary regions. The toxicokinetic and toxicodynamic models were used to simulate dust aerosols binding kinetics in lung airway in that %FEV1 change was also predicted. The mask respirators were applied to control the inhaled dose under dust aerosols exposure. Our results found that only 2% probability the mild ADS events were likely to cause %FEV1 decrement higher than 5%. There were 50% probability of decreasing %FEV1 exceeding 16.9, 18.9, and 7.1% in north, center, and south Taiwan under severe ADS events, respectively. Our result implicates that the use of activated carbon of mask respirators has the best efficacy for reducing inhaled dust aerosol dose, by which the %FEV1 decrement can be reduced up to less than 1%.

ATP promotes cell survival via regulation of cytosolic [Ca2+] and Bcl-2/Bax ratio in lung cancer cells

PubMed Central

Song, Shanshan; Jacobson, Krista N.; McDermott, Kimberly M.; Reddy, Sekhar P.; Cress, Anne E.; Tang, Haiyang; Dudek, Steven M.; Black, Stephen M.; Garcia, Joe G. N.; Makino, Ayako

2015-01-01

Adenosine triphosphate (ATP) is a ubiquitous extracellular messenger elevated in the tumor microenvironment. ATP regulates cell functions by acting on purinergic receptors (P2X and P2Y) and activating a series of intracellular signaling pathways. We examined ATP-induced Ca2+ signaling and its effects on antiapoptotic (Bcl-2) and proapoptotic (Bax) proteins in normal human airway epithelial cells and lung cancer cells. Lung cancer cells exhibited two phases (transient and plateau phases) of increase in cytosolic [Ca2+] ([Ca2+]cyt) caused by ATP, while only the transient phase was observed in normal cells. Removal of extracellular Ca2+ eliminated the plateau phase increase of [Ca2+]cyt in lung cancer cells, indicating that the plateau phase of [Ca2+]cyt increase is due to Ca2+ influx. The distribution of P2X (P2X1-7) and P2Y (P2Y1, P2Y2, P2Y4, P2Y6, P2Y11) receptors was different between lung cancer cells and normal cells. Proapoptotic P2X7 was nearly undetectable in lung cancer cells, which may explain why lung cancer cells showed decreased cytotoxicity when treated with high concentration of ATP. The Bcl-2/Bax ratio was increased in lung cancer cells following treatment with ATP; however, the antiapoptotic protein Bcl-2 demonstrated more sensitivity to ATP than proapoptotic protein Bax. Decreasing extracellular Ca2+ or chelating intracellular Ca2+ with BAPTA-AM significantly inhibited ATP-induced increase in Bcl-2/Bax ratio, indicating that a rise in [Ca2+]cyt through Ca2+ influx is the critical mediator for ATP-mediated increase in Bcl-2/Bax ratio. Therefore, despite high ATP levels in the tumor microenvironment, which would induce cell apoptosis in normal cells, the decreased P2X7 and elevated Bcl-2/Bax ratio in lung cancer cells may enable tumor cells to survive. Increasing the Bcl-2/Bax ratio by exposure to high extracellular ATP may, therefore, be an important selective pressure promoting transformation and cancer progression. PMID:26491047

In patients with a tumour invading the phrenic nerve does prophylactic diaphragm plication improve postoperative lung function?

PubMed

Beattie, Gwyn W; Dunn, William G; Asif, Mohammed

2016-09-01

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was 'In patients with tumours involving the phrenic nerve, does prophylactic diaphragm plication improve lung function following tumour resection?' Using the reported search, 258 papers were found of which 6 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. Three case reports and one case series represent 37 patients in the literature along with two relevant animal studies. Patients treated with prophylactic plication at the time of injury or sacrifice of the phrenic nerve had reduced radiological evidence of diaphragm paralysis, lower reported shortness of breath and reduced requirement for ventilatory support. In patients with prophylactic diaphragm plication and a concurrent pulmonary resection, the predicted postoperative lung function correlated closely with the postoperative measured FEV1, FVC and gas transfer. The postoperative measured FEV1 was reported as 86-98%, the FVC 82-89% and gas transfer 97% of the predicted values. Two animal models investigate the mechanics of respiration, spirometry and gas exchange following diaphragmatic plication. A randomized control study in four dogs measured a 50% reduction in tidal volume and respiratory rate, a 40% decrease in arterial PO2 and a 43% increase in arterial CO2 when the phrenic nerve was crushed in animals with a pneumonectomy but without prophylactic diaphragm plication. A further randomized control animal study with 28 dogs found that plicating the diaphragm after unilateral phrenic nerve transection resulted in a significant increase in tidal volume and lung compliance and a significant decrease in respiratory frequency and the work of breathing. Prophylactic diaphragm plication may preserve lung function, reduce the risk of ventilator dependence and improve the mechanics of breathing in patients with phrenic nerve transection. If transection of the phrenic nerve occurs, and it is recognized intraoperatively, prophylactic diaphragm plication should be considered. © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

75 FR 19921 - Revisions to the Arizona State Implementation Plan

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-16

... are harmful to human health and the environment, including premature mortality, aggravation of respiratory and cardiovascular disease, decreased lung function, visibility impairment, and damage to... or preempt tribal law. List of Subjects in 40 CFR Part 52 Environmental protection, Air pollution...

Quantitative CT characterization of pediatric lung development using routine clinical imaging

PubMed Central

Stein, Jill M.; Walkup, Laura L.; Brody, Alan S.; Fleck, Robert J.

2016-01-01

Background The use of quantitative CT analysis in children is limited by lack of normal values of lung parenchymal attenuation. These characteristics are important because normal lung development yields significant parenchymal attenuation changes as children age. Objective To perform quantitative characterization of normal pediatric lung parenchymal X-ray CT attenuation under routine clinical conditions in order to establish a baseline comparison to that seen in pathological lung conditions. Materials and methods We conducted a retrospective query of normal CT chest examinations in children ages 0–7 years from 2004 to 2014 using standard clinical protocol. During these examinations semi-automated lung parenchymal segmentation was performed to measure lung volume and mean lung attenuation. Results We analyzed 42 CT examinations in 39 children, ages 3 days to 83 months (mean ± standard deviation [SD] = 42±27 months). Lung volume ranged 0.10–1.72 liters (L). Mean lung attenuation was much higher in children younger than 12 months, with values as high as −380 Hounsfield units (HU) in neonates (lung volume 0.10 L). Lung volume decreased to approximately −650 HU by age 2 years (lung volume 0.47 L), with subsequently slower exponential decrease toward a relatively constant value of −860 HU as age and lung volume increased. Conclusion Normal lung parenchymal X-ray CT attenuation decreases with increasing lung volume and age; lung attenuation decreases rapidly in the first 2 years of age and more slowly thereafter. This change in normal lung attenuation should be taken into account as quantitative CT methods are translated to pediatric pulmonary imaging. PMID:27576458

Effects of copper nanoparticle exposure on host defense in a murine pulmonary infection model

PubMed Central

2011-01-01

Background Human exposure to nanoparticles (NPs) and environmental bacteria can occur simultaneously. NPs induce inflammatory responses and oxidative stress but may also have immune-suppressive effects, impairing macrophage function and altering epithelial barrier functions. The purpose of this study was to assess the potential pulmonary effects of inhalation and instillation exposure to copper (Cu) NPs using a model of lung inflammation and host defense. Methods We used Klebsiella pneumoniae (K.p.) in a murine lung infection model to determine if pulmonary bacterial clearance is enhanced or impaired by Cu NP exposure. Two different exposure modes were tested: sub-acute inhalation (4 hr/day, 5 d/week for 2 weeks, 3.5 mg/m3) and intratracheal instillation (24 hr post-exposure, 3, 35, and 100 μg/mouse). Pulmonary responses were evaluated by lung histopathology plus measurement of differential cell counts, total protein, lactate dehydrogenase (LDH) activity, and inflammatory cytokines in bronchoalveolar lavage (BAL) fluid. Results Cu NP exposure induced inflammatory responses with increased recruitment of total cells and neutrophils to the lungs as well as increased total protein and LDH activity in BAL fluid. Both inhalation and instillation exposure to Cu NPs significantly decreased the pulmonary clearance of K.p.-exposed mice measured 24 hr after bacterial infection following Cu NP exposure versus sham-exposed mice also challenged with K.p (1.4 × 105 bacteria/mouse). Conclusions Cu NP exposure impaired host defense against bacterial lung infections and induced a dose-dependent decrease in bacterial clearance in which even our lowest dose demonstrated significantly lower clearance than observed in sham-exposed mice. Thus, exposure to Cu NPs may increase the risk of pulmonary infection. PMID:21943386

[The prevention and therapeutics effect of sodium bicarbonate with gastric lavage, atomization inhalation and intravenous injection on the patients with paraquat poisoning and pulmonary fibrosis induced by paraquat poisoning].

PubMed

Ren, Ainong; Ren, Siqing; Jian, Xiangdong; Zhang, Qing

2015-09-01

To observe the prevention effects of patients with lung exudation and pulmonary fibrosis induced by paraquat poisoning in sodium bicarbonate (SB) with gastric lavage, atomization inhalation and intravenous injection. To collect 38 patients with paraquat poisoning in hospital, after poison immediately with gastric lavage of 1.5% SB, and atomization inhalation of 5% SB 10~15 ml twice daily and intravenous injection of 5% SB twice a day, continuous application of 5~7 days. and the HRCT score and liver and kidney function was performed on patients with lung after treatment. And the extraction of 38 SB patients with previously untreated with SB for comparison. Lung HRCT average score in 72 h, 7 d, 30 d on patients with paraquat poisoning untreated with SB reached 2.87, 3.12, 2.13, HRCT display shows that the appearance of the wear glass shadow, grid shadow, honeycomb shadow, and other signs of fibrosis. Average HRCT reached 1.95, 2.20, 1.67 on patients treated with SB,signs of lung exudation and fibrosis was significantly reduced,compare two groups,there was statistically significance (P<0.01). And compared to the control group, activity of serum alanine aminotransferase (ALT) and aspartic acid transaminase (AST) decreased significantly in group of paraquat poisoning with triple application of SB, the level of serum urea nitrogen (BUN) and creatinine (Cr) significantly decreased, the difference is statistically significant (P<0.01). The triple application of SB can reduced the pulmonary fibrosis and effusion induced by paraquat poisoning,and protective effect on the function of liver and kidney is obvious, suggesting that the method for treatment of paraquat poisoning, prevention of paraquat lung and improve survival rate has the exact effect.

Imaging Phenotype of Occupational Endotoxin-Related Lung Function Decline.

PubMed

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

2016-09-01

Although occupational exposures contribute to a significant proportion of obstructive lung disease, the phenotype of obstructive lung disease associated with work-related organic dust exposure independent of smoking remains poorly defined. We identified the relative contributions of smoking and occupational endotoxin exposure to parenchymal and airway remodeling as defined by quantitative computed tomography (CT). The Shanghai Textile Worker Study is a longitudinal study of endotoxin-exposed cotton workers and endotoxin-unexposed silk workers that was initiated in 1981. Spirometry, occupational endotoxin exposure, and smoking habits were assessed at 5-year intervals. High-resolution computed tomography (CT) was performed in 464 retired workers in 2011, along with quantitative lung densitometric and airway analysis. Significant differences in all CT measures were noted across exposure groups. Occupational endotoxin exposure was associated with a decrease (-1.3%) in percent emphysema (LAAI-950), a 3.3-Hounsfield unit increase in 15th percentile density, an 18.1-g increase in lung mass, and a 2.3% increase in wall area percent. Current but not former smoking was associated with a similar CT phenotype. Changes in LAAI-950 were highly correlated with 15th percentile density (correlation -1.0). Lung mass was the only measure associated with forced expiratory volume in 1 sec (FEV1) decline, with each 10-g increase in lung mass associated with an additional loss (-6.1 mL) of FEV1 (p = 0.001) between 1981 and 2011. There are many similarities between the effects of occupational endotoxin exposure and those of tobacco smoke exposure on lung parenchyma and airway remodeling. The effects of occupational endotoxin exposure appear to persist even after the cessation of exposure. LAAI-950 may not be a reliable indicator of emphysema in subjects without spirometric impairment. Lung mass is a CT-based biomarker of accelerated lung function decline. 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.

Determinants of 6-minute walk distance in patients with idiopathic pulmonary fibrosis undergoing lung transplant evaluation.

PubMed

Porteous, Mary K; Rivera-Lebron, Belinda N; Kreider, Maryl; Lee, James; Kawut, Steven M

2016-03-01

Little is known about the physiologic determinants of 6-minute walk distance in idiopathic pulmonary fibrosis. We investigated the demographic, pulmonary function, echocardiographic, and hemodynamic determinants of 6-minute walk distance in patients with idiopathic pulmonary fibrosis evaluated for lung transplantation. We performed a cross-sectional analysis of 130 patients with idiopathic pulmonary fibrosis who completed a lung transplantation evaluation at the Hospital of the University of Pennsylvania between 2005 and 2010. Multivariable linear regression analysis was used to generate an explanatory model for 6-minute walk distance. After adjustment for age, sex, race, height, and weight, the presence of right ventricular dilation was associated with a decrease of 50.9 m (95% confidence interval [CI], 8.4-93.3) in 6-minute walk distance ([Formula: see text]). For each 200-mL reduction in forced vital capacity, the walk distance decreased by 15.0 m (95% CI, 9.0-21.1; [Formula: see text]). For every increase of 1 Wood unit in pulmonary vascular resistance, the walk distance decreased by 17.3 m (95% CI, 5.1-29.5; [Formula: see text]). Six-minute walk distance in idiopathic pulmonary fibrosis depends in part on circulatory impairment and the degree of restrictive lung disease. Future trials that target right ventricular morphology, pulmonary vascular resistance, and forced vital capacity may potentially improve exercise capacity in patients with idiopathic pulmonary fibrosis.

Experience with perioperative pirfenidone for lung cancer surgery in patients with idiopathic pulmonary fibrosis.

PubMed

Iwata, Takekazu; Yoshida, Shigetoshi; Nagato, Kaoru; Nakajima, Takahiro; Suzuki, Hidemi; Tagawa, Tetsuzo; Mizobuchi, Teruaki; Ota, Satoshi; Nakatani, Yukio; Yoshino, Ichiro

2015-10-01

Idiopathic pulmonary fibrosis (IPF) is a progressive diffuse lung disease associated with an increased risk of lung cancer. Patients with IPF sometimes develop a life-threatening acute exacerbation of IPF (AE-IPF) after lung cancer surgery. In this retrospective study, pirfenidone, an antifibrotic agent, was perioperatively administered to IPF patients with lung cancer with the aim of preventing postoperative AE-IPF, and the feasibility and clinical outcomes were investigated. Twelve IPF patients with concomitant lung cancer who received perioperative pirfenidone treatment (PPT) for lung cancer surgery were retrospectively investigated. Sixteen IPF patients undergoing lung cancer surgery without PPT were analyzed as historical controls. Compared to the controls, the PPT patients had a more severely impaired preoperative pulmonary function and a larger number of limited pulmonary resections. There was a significant preoperative decrease in the serum KL-6 levels of the PPT patients. No severe pirfenidone-related complications or IPF-related events occurred in the PPT patients, while six control patients developed AE-IPF (P = 0.0167). A quantitative histopathological evaluation of resected lung specimens found that tissue changes associated with IPF were significantly fewer in the PPT patients (P = 0.021). PPT is a feasible perioperative treatment for IPF patients with lung cancer. Its effectiveness in preventing postoperative AE-IPF thus warrants prospective verification.

Angiotensin-I converting enzyme inhibitory peptides from antihypertensive skate (Okamejei kenojei) skin gelatin hydrolysate in spontaneously hypertensive rats.

PubMed

Ngo, Dai-Hung; Kang, Kyong-Hwa; Ryu, BoMi; Vo, Thanh-Sang; Jung, Won-Kyo; Byun, Hee-Guk; Kim, Se-Kwon

2015-05-01

The aim of this study was to investigate antihypertensive effect of bioactive peptides from skate (Okamejei kenojei) skin gelatin. The Alcalase/protease gelatin hydrolysate below 1 kDa (SAP) exhibited the highest angiotensin-I converting enzyme (ACE) inhibition compared to other hydrolysates. SAP can decrease systolic blood pressure significantly in spontaneously hypertensive rats. SAP inhibited vasoconstriction via PPAR-γ expression, activation and phosphorylation of eNOS in lungs. Moreover, the expression levels of endothelin-1, RhoA, α-smooth muscle actin, cleaved caspase 3 and MAPK were decreased by SAP in lungs. Vascularity, muscularization and cellular proliferation in lungs were detected by immunohistochemical staining. Finally, two purified peptides (LGPLGHQ, 720Da and MVGSAPGVL, 829Da) showed potent ACE inhibition with IC50 values of 4.22 and 3.09 μM, respectively. These results indicate that bioactive peptides isolated from skate skin gelatin may serve as candidates against hypertension and could be used as functional food ingredients. Copyright © 2014 Elsevier Ltd. All rights reserved.

Functional mechanism of lung mosaic CT attenuation: assessment with deep-inspiration breath-hold perfusion SPECT-CT fusion imaging and non-breath-hold Technegas SPECT.

PubMed

Suga, K; Yasuhiko, K; Iwanaga, H; Tokuda, O; Matsunaga, N

2009-01-01

The functional mechanism of lung mosaic computed tomography attenuation (MCA) in pulmonary vascular disease (PVD) and obstructive airway disease (OAD) has not yet been fully clarified. To clarify the mechanism of MCA in these diseases by assessing the relationship between regional lung function and CT attenuation change at MCA sites with the use of automated deep-inspiratory breath-hold (DIBrH) perfusion single-photon emission computed tomography (SPECT)-CT fusion images and non-breath-hold Technegas SPECT. Subjects were 42 PVD patients (31 pulmonary thromboembolism, four primary/two secondary pulmonary hypertension, and five Takayasu arteritis), 12 OAD patients (five acute asthma, four obliterative bronchiolitis, and three bronchiectasis), and 12 normal controls, all of whom had MCA on DIBrH CT. The relationship between regional lung function and CT attenuation change at the lung slices with MCA was assessed using DIBrH perfusion SPECT-CT fusion images and non-breath-hold Technegas SPECT. The severity of perfusion defects with or without MCA was quantified by regions-of-interest analysis. On DIBrH CT and perfusion SPECT, in contrast to no noticeable CT attenuation abnormality and fairly uniform perfusion in controls, 60 MCA and 274 perfusion defects in PVD patients, and 18 MCA and 61 defects in OAD patients were identified, with a total of 77 ventilation defects on Technegas SPECT in all patients. SPECT-CT correlation showed that, throughout the 78 MCA sites of all patients, lung perfusion was persistently decreased at low CT attenuation and preserved at intervening high CT attenuation, while lung ventilation was poorly correlated with CT attenuation change. The radioactivity ratios of reduced perfusion and the intervening preserved perfusion at the 78 perfusion defects with MCA were significantly lower than those at the remaining 257 defects without MCA (P<0.0001). Although further validation is required, our results indicate that heterogeneous pulmonary arterial perfusion may be a dominant mechanism of MCA in PVD and OAD.

Aging effects on airflow dynamics and lung function in human bronchioles.

PubMed

Kim, JongWon; Heise, Rebecca L; Reynolds, Angela M; Pidaparti, Ramana M

2017-01-01

The mortality rate for patients requiring mechanical ventilation is about 35% and this rate increases to about 53% for the elderly. In general, with increasing age, the dynamic lung function and respiratory mechanics are compromised, and several experiments are being conducted to estimate these changes and understand the underlying mechanisms to better treat elderly patients. Human tracheobronchial (G1 ~ G9), bronchioles (G10 ~ G22) and alveolar sacs (G23) geometric models were developed based on reported anatomical dimensions for a 50 and an 80-year-old subject. The aged model was developed by altering the geometry and material properties of the model developed for the 50-year-old. Computational simulations using coupled fluid-solid analysis were performed for geometric models of bronchioles and alveolar sacs under mechanical ventilation to estimate the airflow and lung function characteristics. The airway mechanical characteristics decreased with aging, specifically a 38% pressure drop was observed for the 80-year-old as compared to the 50-year-old. The shear stress on airway walls increased with aging and the highest shear stress was observed in the 80-year-old during inhalation. A 50% increase in peak strain was observed for the 80-year-old as compared to the 50-year-old during exhalation. The simulation results indicate that there is a 41% increase in lung compliance and a 35%-50% change in airway mechanical characteristics for the 80-year-old in comparison to the 50-year-old. Overall, the airway mechanical characteristics as well as lung function are compromised due to aging. Our study demonstrates and quantifies the effects of aging on the airflow dynamics and lung capacity. These changes in the aging lung are important considerations for mechanical ventilation parameters in elderly patients. Realistic geometry and material properties need to be included in the computational models in future studies.

Aging effects on airflow dynamics and lung function in human bronchioles

PubMed Central

Kim, JongWon; Heise, Rebecca L.; Reynolds, Angela M.; Pidaparti, Ramana M.

2017-01-01

Background and objective The mortality rate for patients requiring mechanical ventilation is about 35% and this rate increases to about 53% for the elderly. In general, with increasing age, the dynamic lung function and respiratory mechanics are compromised, and several experiments are being conducted to estimate these changes and understand the underlying mechanisms to better treat elderly patients. Materials and methods Human tracheobronchial (G1 ~ G9), bronchioles (G10 ~ G22) and alveolar sacs (G23) geometric models were developed based on reported anatomical dimensions for a 50 and an 80-year-old subject. The aged model was developed by altering the geometry and material properties of the model developed for the 50-year-old. Computational simulations using coupled fluid-solid analysis were performed for geometric models of bronchioles and alveolar sacs under mechanical ventilation to estimate the airflow and lung function characteristics. Findings The airway mechanical characteristics decreased with aging, specifically a 38% pressure drop was observed for the 80-year-old as compared to the 50-year-old. The shear stress on airway walls increased with aging and the highest shear stress was observed in the 80-year-old during inhalation. A 50% increase in peak strain was observed for the 80-year-old as compared to the 50-year-old during exhalation. The simulation results indicate that there is a 41% increase in lung compliance and a 35%-50% change in airway mechanical characteristics for the 80-year-old in comparison to the 50-year-old. Overall, the airway mechanical characteristics as well as lung function are compromised due to aging. Conclusion Our study demonstrates and quantifies the effects of aging on the airflow dynamics and lung capacity. These changes in the aging lung are important considerations for mechanical ventilation parameters in elderly patients. Realistic geometry and material properties need to be included in the computational models in future studies. PMID:28846719

Acute changes in lung function associated with proximity to a steel plant: a randomized study.

PubMed

Dales, Robert; Kauri, Lisa Marie; Cakmak, Sabit; Mahmud, Mamun; Weichenthal, Scott A; Van Ryswyk, Keith; Kumarathasan, Premkumari; Thomson, Errol; Vincent, Renaud; Broad, Gayle; Liu, Ling

2013-05-01

Steel production is a major industry worldwide yet there is relatively little information on the pulmonary effects of air quality near steel manufacturing plants. The aim of this study was to examine how lung function changes acutely when healthy subjects are situated near a steel plant which is adjacent to a residential area. Sixty-one subjects were randomly assigned to spend 5 consecutive, 8-hour days in a residential neighborhood approximately 0.9km from a steel plant, or approximately 4.5km away at a college campus. Subjects crossed-over between sites after a nine-day washout period. Lung function was measured daily at both sites along with air pollutants including SO2, NO2, O3, PM2.5, and ultrafine particles. Diffusion capacity and pulse oximetry were also examined. Compared with the college site, the forced expiratory volume in 1-second/forced vital capacity, forced expiratory flow between 25% and 75% of the FVC, total lung capacity, functional residual capacity, and residual volume were lower near the steel plant by 0.67% (95% CI: 0.28, 1.06),1.62% (95% CI: 0.50, 2.75), 1.54% (95% CI: 0.68, 2.39), 3.54% (95% CI: 1.95, 5.13) and 11.3% (95% CI: 4.92, 17.75), respectively. Diffusion capacity, forced expiratory volume in 1s, and pulse oximetry were also lower near the plant but these effects were not statistically significant. Sulfur dioxide, ultrafine particulates, and oxides of nitrogen were greater near the steel plant site compared to the college site. Spending short periods of time near a steel plant is associated with a decrease in lung function. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

Dual-energy micro-CT imaging of pulmonary airway obstruction: correlation with micro-SPECT

NASA Astrophysics Data System (ADS)

Badea, C. T.; Befera, N.; Clark, D.; Qi, Y.; Johnson, G. A.

2014-03-01

To match recent clinical dual energy (DE) CT studies focusing on the lung, similar developments for DE micro-CT of the rodent lung are required. Our group has been actively engaged in designing pulmonary gating techniques for micro- CT, and has also introduced the first DE micro-CT imaging method of the rodent lung. The aim of this study was to assess the feasibility of DE micro-CT imaging for the evaluation of airway obstruction in mice, and to compare the method with micro single photon emission computed tomography (micro-SPECT) using technetium-99m labeled macroaggregated albumin (99mTc-MAA). The results suggest that the induced pulmonary airway obstruction causes either atelectasis, or air-trapping similar to asthma or chronic bronchitis. Atelectasis could only be detected at early time points in DE micro-CT images, and is associated with a large increase in blood fraction and decrease in air fraction. Air trapping had an opposite effect with larger air fraction and decreased blood fraction shown by DE micro-CT. The decrease in perfusion to the hypoventilated lung (hypoxic vasoconstriction) is also seen in micro-SPECT. The proposed DE micro-CT technique for imaging localized airway obstruction performed well in our evaluation, and provides a higher resolution compared to micro-SPECT. Both DE micro-CT and micro-SPECT provide critical, quantitative lung biomarkers for image-based anatomical and functional information in the small animal. The methods are readily linked to clinical methods allowing direct comparison of preclinical and clinical results.

Effect of pirfenidone on wound healing in lung transplant patients.

PubMed

Mortensen, Amber; Cherrier, Lauren; Walia, Rajat

2018-01-01

The drug pirfenidone has been shown to slow the progression and decrease mortality of idiopathic pulmonary fibrosis (IPF). Its exact mechanism is unknown, but it likely inhibits pro-fibrotic cytokine transforming growth factor beta, a known contributor to wound healing. We evaluated whether patients taking pirfenidone until lung transplantation had increased risk of impaired wound healing post-transplant. This information could determine whether pirfenidone should be discontinued prior to listing to allow for a wash-out period. We retrospectively reviewed patients who underwent lung transplantation for pulmonary fibrosis at Norton Thoracic Institute in Phoenix, Arizona, from January 2014 to December 2015. We describe 18 patients who took pirfenidone up to a month before transplant. Aside from one patient who experienced sternal dehiscence due to a surgical issue, all remaining patients did well with no evidence of airway dehiscence. Each of these 17 patients had been on pirfenidone for at least 30 days; nine patients had been on pirfenidone for over 90 days. Baseline characteristics including age, sex, body mass index, renal function, liver function, glucose level, pre-transplant corticosteroid use, and post-transplant immunosuppressant therapy were similar. In our experience, pirfenidone may be safely continued until lung transplantation. Only one patient in our series experienced impaired wound healing related to a surgical issue, even when pirfenidone was continued until lung transplantation. We found no evidence of impaired wound healing or airway complications after lung transplantation in patients who were treated with pirfenidone before lung transplantation.

Deacetylmycoepoxydiene is an agonist of Rac1, and simultaneously induces autophagy and apoptosis.

PubMed

Xie, Wei; Zhang, Wei; Sun, Mingwei; Lu, Chunhua; Shen, Yuemao

2018-05-09

Lung cancer is the second most common cause of cancer-related death in the world. Most cases of lung cancer are not curable, especially non-small cell lung cancer (NSCLC). Thus, novel treatment targets for this malignant disease are urgently needed. Here, we demonstrate the feasibility of Rac1 in treating p53-null human NSCLC H1299 as a novel drug target. Deacetylmycoepoxydiene (DA-MED), a cytotoxic natural polyketide, functions as a Rac1 agonist in p53-null NSCLC H1299 cells. DA-MED treatment drives Rac1 activation and promotes robust production of reactive oxygen species, activating mitochondrial permeability transition and the intrinsic apoptotic pathway. Knockdown of Rac1 decreases ROS production in DA-MED-treated cells, resulting in a concomitant decrease in DA-MED-induced apoptosis. DA-MED-activated Rac1 induces autophagy by inhibiting mammalian target of rapamycin, leading to anti-apoptotic and anti-metastatic effects. Therefore, this study provides novel insight into the complex cytotoxic and pro-survival mechanisms associated with a potent Rac1 agonist and suggests that further development of more potent Rac1 agonists could be an effective strategy for future non-small cell lung cancer treatments.

[Lung volume reduction surgery in advanced emphysema--results of the Washington University, St. Louis].

PubMed

Cooper, J D; Gaissert, H A; Patterson, G A; Pohl, M S; Yusen, R D; Trulock, E P

1996-01-01

The aim of lung volume reduction surgery is to alleviate the symptoms of severe emphysema and to improve the life quality of the patient. The appropriate candidates (approximately 20% of all emphysematic patients examined in our clinic) had considerable dyspnea, an increased lung capacity, and a heterogenous dissemination of the emphysema with regional destruction of the parenchyma, hyperinflation and poor perfusion. After preoperative physiotherapie with a specified rehabilitation aim, a resection of 20 to 30% of the total lung volume was performed via sternotomy. From January 1993 to February 1996, 150 patients underwent bilateral lung volume reduction (age range = 36 to 77 years). The mean forced expiratory volume in 1 s (FEV1) was preoperatively 25% of the predicted value, the total lung capacity (TLC) 142% and the residual volume (RV) 283%, 94% of these patients necessitated oxygen supply at rest or during exercise. The 90-day mortality was 4%. All patients except 1 were extubated immediately after operation. The median hospital stay was 10 days in the first 100 patients and 7 days in the last 50. An increase of the FEV1 by 51% and a decrease of the RV by 28% was observed 6 months after operation. The mean PaO2 was improved by 8 mm Hg while the percentage of oxygen dependent patients went down from 50 to 16%. In addition a raise of the perseverance capacity, a clear decrease of dyspnea and an improvement of the life quality were achieved. These results persist after 1 (n = 56) and 2 (n = 20) years after operation. Lung volume reduction leads to an improvement of the lung function, symptoms and the quality of life, which is superior to that achieved by maximal clinical intervention.

Overexpression of TRPV3 Correlates with Tumor Progression in Non-Small Cell Lung Cancer.

PubMed

Li, Xiaolei; Zhang, Qianhui; Fan, Kai; Li, Baiyan; Li, Huifeng; Qi, Hanping; Guo, Jing; Cao, Yonggang; Sun, Hongli

2016-03-24

(1) BACKGROUND: Transient receptor potential vanilloid 3 (TRPV3) is a member of the TRP channels family of Ca(2+)-permeant channels. The proteins of some TRP channels are highly expressed in cancer cells. This study aimed to assess the clinical significance and biological functions of TRPV3 in non-small cell lung cancer (NSCLC); (2) METHODS: Immunohistochemistry was used to detect the expression of TRPV3 in NSCLC tissues and adjacent noncancerous lung tissues. Western blot was used to detect the protein expressions of TRPV3, CaMKII, p-CaMKII, CyclinA, CyclinD, CyclinE1, CDK2, CDK4, and P27. Small interfering RNA was used to deplete TRPV3 expression. A laser scanning confocal microscope was used to measure intracellular calcium concentration ([Ca(2+)]i). Flow cytometry was used to analyze cell cycle; (3) RESULTS: TRPV3 was overexpressed in 65 of 96 (67.7%) human lung cancer cases and correlated with differentiation (p = 0.001) and TNM stage (p = 0.004). Importantly, TRPV3 expression was associated with short overall survival. In addition, blocking or knockdown of TRPV3 could inhibit lung cancer cell proliferation. Moreover, TRPV3 inhibition could decrease [Ca(2+)]i of lung cancer cells and arrest cell cycle at the G1/S boundary. Further results revealed that TRPV3 inhibition decreased expressions of p-CaMKII, CyclinA, CyclinD1, CyclinE, and increased P27 level; (4) CONCLUSIONS: Our findings demonstrate that TRPV3 was overexpressed in NSCLC and correlated with lung cancer progression. TRPV3 activation could promote proliferation of lung cancer cells. TRPV3 might serve as a potential companion drug target in NSCLC.

Lung volumes and lung volume recruitment in ARDS: a comparison between supine and prone position.

PubMed

Aguirre-Bermeo, Hernan; Turella, Marta; Bitondo, Maddalena; Grandjean, Juan; Italiano, Stefano; Festa, Olimpia; Morán, Indalecio; Mancebo, Jordi

2018-02-14

The use of positive end-expiratory pressure (PEEP) and prone position (PP) is common in the management of severe acute respiratory distress syndrome patients (ARDS). We conducted this study to analyze the variation in lung volumes and PEEP-induced lung volume recruitment with the change from supine position (SP) to PP in ARDS patients. The investigation was conducted in a multidisciplinary intensive care unit. Patients who met the clinical criteria of the Berlin definition for ARDS were included. The responsible physician set basal PEEP. To avoid hypoxemia, FiO 2 was increased to 0.8 1 h before starting the protocol. End-expiratory lung volume (EELV) and functional residual capacity (FRC) were measured using the nitrogen washout/washin technique. After the procedures in SP, the patients were turned to PP and 1 h later the same procedures were made in PP. Twenty-three patients were included in the study, and twenty were analyzed. The change from SP to PP significantly increased FRC (from 965 ± 397 to 1140 ± 490 ml, p = 0.008) and EELV (from 1566 ± 476 to 1832 ± 719 ml, p = 0.008), but PEEP-induced lung volume recruitment did not significantly change (269 ± 186 ml in SP to 324 ± 188 ml in PP, p = 0.263). Dynamic strain at PEEP decreased with the change from SP to PP (0.38 ± 0.14 to 0.33 ± 0.13, p = 0.040). As compared to supine, prone position increases resting lung volumes and decreases dynamic lung strain.

Overexpression of TRPV3 Correlates with Tumor Progression in Non-Small Cell Lung Cancer

PubMed Central

Li, Xiaolei; Zhang, Qianhui; Fan, Kai; Li, Baiyan; Li, Huifeng; Qi, Hanping; Guo, Jing; Cao, Yonggang; Sun, Hongli

2016-01-01

(1) Background: Transient receptor potential vanilloid 3 (TRPV3) is a member of the TRP channels family of Ca2+-permeant channels. The proteins of some TRP channels are highly expressed in cancer cells. This study aimed to assess the clinical significance and biological functions of TRPV3 in non-small cell lung cancer (NSCLC); (2) Methods: Immunohistochemistry was used to detect the expression of TRPV3 in NSCLC tissues and adjacent noncancerous lung tissues. Western blot was used to detect the protein expressions of TRPV3, CaMKII, p-CaMKII, CyclinA, CyclinD, CyclinE1, CDK2, CDK4, and P27. Small interfering RNA was used to deplete TRPV3 expression. A laser scanning confocal microscope was used to measure intracellular calcium concentration ([Ca2+]i). Flow cytometry was used to analyze cell cycle; (3) Results: TRPV3 was overexpressed in 65 of 96 (67.7%) human lung cancer cases and correlated with differentiation (p = 0.001) and TNM stage (p = 0.004). Importantly, TRPV3 expression was associated with short overall survival. In addition, blocking or knockdown of TRPV3 could inhibit lung cancer cell proliferation. Moreover, TRPV3 inhibition could decrease [Ca2+]i of lung cancer cells and arrest cell cycle at the G1/S boundary. Further results revealed that TRPV3 inhibition decreased expressions of p-CaMKII, CyclinA, CyclinD1, CyclinE, and increased P27 level; (4) Conclusions: Our findings demonstrate that TRPV3 was overexpressed in NSCLC and correlated with lung cancer progression. TRPV3 activation could promote proliferation of lung cancer cells. TRPV3 might serve as a potential companion drug target in NSCLC. PMID:27023518

Inhibition of Myocardin-Related Transcription Factor/Serum Response Factor Signaling Decreases Lung Fibrosis and Promotes Mesenchymal Cell Apoptosis

PubMed Central

Sisson, Thomas H.; Ajayi, Iyabode O.; Subbotina, Natalya; Dodi, Amos E.; Rodansky, Eva S.; Chibucos, Lauren N.; Kim, Kevin K.; Keshamouni, Venkateshwar G.; White, Eric S.; Zhou, Yong; Higgins, Peter D.R.; Larsen, Scott D.; Neubig, Richard R.; Horowitz, Jeffrey C.

2016-01-01

Myofibroblasts are crucial to the pathogenesis of tissue fibrosis. Their formation of stress fibers results in the release of myocardin-related transcription factor (MRTF), a transcriptional coactivator of serum response factor (SRF). MRTF-A (Mkl1)-deficient mice are protected from lung fibrosis. We hypothesized that the SRF/MRTF pathway inhibitor CCG-203971 would modulate myofibroblast function in vitro and limit lung fibrosis in vivo. Normal and idiopathic pulmonary fibrosis lung fibroblasts were treated with/without CCG-203971 (N-[4-chlorophenyl]-1-[3-(2-furanyl)benzoyl]-3-piperidine carboxamide) and/or Fas-activating antibody in the presence/absence of transforming growth factor (TGF)-β1, and apoptosis was assessed. In vivo studies examined the effect of therapeutically administered CCG-203971 on lung fibrosis in two distinct murine models of fibrosis induced by bleomycin or targeted type II alveolar epithelial injury. In vitro, CCG-203971 prevented nuclear localization of MRTF-A; increased the apoptotic susceptibility of normal and idiopathic pulmonary fibrosis fibroblasts; blocked TGF-β1–induced myofibroblast differentiation; and inhibited TGF-β1–induced expression of fibronectin, X-linked inhibitor of apoptosis, and plasminogen activator inhibitor-1. TGF-β1 did not protect fibroblasts or myofibroblasts from apoptosis in the presence of CCG-203971. In vivo, CCG-203971 significantly reduced lung collagen content in both murine models while decreasing alveolar plasminogen activator inhibitor-1 and promoting myofibroblast apoptosis. These data support a central role of the SRF/MRTF pathway in the pathobiology of lung fibrosis and suggest that its inhibition can help resolve lung fibrosis by promoting fibroblast apoptosis. PMID:25681733

Impact of endobronchial coiling on segmental bronchial lumen in treated and untreated lung lobes: Correlation with changes in lung volume, clinical and pulmonary function tests.

PubMed

Kloth, C; Thaiss, W M; Hetzel, J; Ditt, H; Grosse, U; Nikolaou, K; Horger, M

2016-07-01

To assess the impact of endobronchial coiling on the segment bronchus cross-sectional area and volumes in patients with lung emphysema using quantitative chest-CT measurements. Thirty patients (female = 15; median age = 65.36 years) received chest-CT before and after endobronchial coiling for lung volume reduction (LVR) between January 2010 and December 2014. Thin-slice (0.6 mm) non-enhanced image data sets were acquired both at end-inspiration and end-expiration using helical technique and 120 kV/100-150 mAs. Clinical response was defined as an increase in the walking distance (Six-minute walk test; 6MWT) after LVR-therapy. Additionally, pulmonary function test (PFT) measurements were used for clinical correlation. In the treated segmental bronchia, the cross-sectional lumen area showed significant reduction (p < 0.05) in inspiration and tendency towards enlargement in expiration (p > 0.05). In the ipsilateral lobes, the lumina showed no significant changes. In the contralateral lung, we found tendency towards increased cross-sectional area in inspiration (p = 0.06). Volumes of the treated segments correlated with the treated segmental bronchial lumina in expiration (r = 0.80, p < 0.001). Clinical correlation with changes in 6MWT/PFT showed a significant decrease of the inspiratory volume of the treated lobe in responders only. Endobronchial coiling causes significant decrease in the cross-sectional area of treated segment bronchi in inspiration and a slight increase in expiration accompanied by a volume reduction. • Endobronchial coiling has indirect impact on cross-sectional area of treated segment bronchi • Volume changes of treated lobes correlate with changes in bronchial cross-sectional area • Coil-induced effects reflect their stabilizing and stiffening impact on lung parenchyma • Endobronchial coiling reduces bronchial collapsing compensating the loss of elasticity.

Clinical and Radiographic Predictors of GOLD–Unclassified Smokers in the COPDGene Study

PubMed Central

Hokanson, John E.; Murphy, James R.; Regan, Elizabeth A.; Make, Barry J.; Lynch, David A.; Crapo, James D.; Silverman, Edwin K.

2011-01-01

Rationale: A significant proportion of smokers have lung function impairment characterized by a reduced FEV1 with a preserved FEV1/FVC ratio. These smokers are a poorly characterized group due to their systematic exclusion from chronic obstructive pulmonary disease (COPD) studies. Objectives: To characterize the clinical, functional, and radiographic features of Global Initiative for Chronic Obstructive Lung Disease (GOLD)-Unclassified (FEV1/FVC ≥ 0.7 and FEV1 < 80% predicted) and lower limits of normal (LLN)-unclassified (FEV1/FVC ≥ LLN and FEV1 < LLN) subjects compared to smokers with normal lung function and subjects with COPD. Methods: Data from the first 2,500 subjects enrolled in the COPDGene study were analyzed. All subjects had 10 or more pack-years of smoking and were between the ages of 45 and 80 years. Multivariate regression models were constructed to determine the clinical and radiological variables associated with GOLD-Unclassified (GOLD-U) and LLN-Unclassified status. Separate multivariate regressions were performed in the subgroups of subjects with complete radiologic measurement variables available. Measurements and Main Results: GOLD-U smokers account for 9% of smokers in COPDGene and have increased body mass index (BMI), a disproportionately reduced total lung capacity, and a higher proportion of nonwhite subjects and subjects with diabetes. GOLD-U subjects exhibit increased airway wall thickness compared to smoking control subjects and decreased gas trapping and bronchodilator responsiveness compared to subjects with COPD. When LLN criteria were used to define the “unclassified” group, African American subjects were no longer overrepresented. Both GOLD-U and LLN-Unclassified subjects demonstrated a wide range of lung function impairment, BMI, and percentage of total lung emphysema. Conclusions: Subjects with reduced FEV1 and a preserved FEV1/FVC ratio are a heterogeneous group with significant symptoms and functional limitation who likely have a variety of underlying etiologies beyond increased BMI. Clinical trial registered with www.clinicaltrials.gov (NCT000608764). PMID:21493737

Metabolic Syndrome Biomarkers Predict Lung Function Impairment

PubMed Central

Naveed, Bushra; Weiden, Michael D.; Kwon, Sophia; Gracely, Edward J.; Comfort, Ashley L.; Ferrier, Natalia; Kasturiarachchi, Kusali J.; Cohen, Hillel W.; Aldrich, Thomas K.; Rom, William N.; Kelly, Kerry; Prezant, David J.

2012-01-01

Rationale: Cross-sectional studies demonstrate an association between metabolic syndrome and impaired lung function. Objectives: To define if metabolic syndrome biomarkers are risk factors for loss of lung function after irritant exposure. Methods: A nested case-control study of Fire Department of New York personnel with normal pre–September 11th FEV1 and who presented for subspecialty pulmonary evaluation before March 10, 2008. We correlated metabolic syndrome biomarkers obtained within 6 months of World Trade Center dust exposure with subsequent FEV1. FEV1 at subspecialty pulmonary evaluation within 6.5 years defined disease status; cases had FEV1 less than lower limit of normal, whereas control subjects had FEV1 greater than or equal to lower limit of normal. Measurements and Main Results: Clinical data and serum sampled at the first monitoring examination within 6 months of September 11, 2001, assessed body mass index, heart rate, serum glucose, triglycerides and high-density lipoprotein (HDL), leptin, pancreatic polypeptide, and amylin. Cases and control subjects had significant differences in HDL less than 40 mg/dl with triglycerides greater than or equal to 150 mg/dl, heart rate greater than or equal to 66 bpm, and leptin greater than or equal to 10,300 pg/ml. Each increased the odds of abnormal FEV1 at pulmonary evaluation by more than twofold, whereas amylin greater than or equal to 116 pg/ml decreased the odds by 84%, in a multibiomarker model adjusting for age, race, body mass index, and World Trade Center arrival time. This model had a sensitivity of 41%, a specificity of 86%, and a receiver operating characteristic area under the curve of 0.77. Conclusions: Abnormal triglycerides and HDL and elevated heart rate and leptin are independent risk factors of greater susceptibility to lung function impairment after September 11, 2001, whereas elevated amylin is protective. Metabolic biomarkers are predictors of lung disease, and may be useful for assessing risk of impaired lung function in response to particulate inhalation. PMID:22095549

WE-AB-202-04: Statistical Evaluation of Lung Function Using 4DCT Ventilation Imaging: Proton Therapy VS IMRT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, Q; Zhang, M; Chen, T

Purpose: Variation in function of different lung regions has been ignored so far for conventional lung cancer treatment planning, which may lead to higher risk of radiation induced lung disease. 4DCT based lung ventilation imaging provides a novel yet convenient approach for lung functional imaging as 4DCT is taken as routine for lung cancer treatment. Our work aims to evaluate the impact of accounting for spatial heterogeneity in lung function using 4DCT based lung ventilation imaging for proton and IMRT plans. Methods: Six patients with advanced stage lung cancer of various tumor locations were retrospectively evaluated for the study. Protonmore » and IMRT plans were designed following identical planning objective and constrains for each patient. Ventilation images were calculated from patients’ 4DCT using deformable image registration implemented by Velocity AI software based on Jacobian-metrics. Lung was delineated into two function level regions based on ventilation (low and high functional area). High functional region was defined as lung ventilation greater than 30%. Dose distribution and statistics in different lung function area was calculated for patients. Results: Variation in dosimetric statistics of different function lung region was observed between proton and IMRT plans. In all proton plans, high function lung regions receive lower maximum dose (100.2%–108.9%), compared with IMRT plans (106.4%–119.7%). Interestingly, three out of six proton plans gave higher mean dose by up to 2.2% than IMRT to high function lung region. Lower mean dose (lower by up to 14.1%) and maximum dose (lower by up to 9%) were observed in low function lung for proton plans. Conclusion: A systematic approach was developed to generate function lung ventilation imaging and use it to evaluate plans. This method hold great promise in function analysis of lung during planning. We are currently studying more subjects to evaluate this tool.« less

Lung parenchymal analysis on dynamic MRI in thoracic insufficiency syndrome to assess changes following surgical intervention

NASA Astrophysics Data System (ADS)

Jagadale, Basavaraj N.; Udupa, Jayaram K.; Tong, Yubing; Wu, Caiyun; McDonough, Joseph; Torigian, Drew A.; Campbell, Robert M.

2018-02-01

General surgeons, orthopedists, and pulmonologists individually treat patients with thoracic insufficiency syndrome (TIS). The benefits of growth-sparing procedures such as Vertical Expandable Prosthetic Titanium Rib (VEPTR)insertionfor treating patients with TIS have been demonstrated. However, at present there is no objective assessment metricto examine different thoracic structural components individually as to their roles in the syndrome, in contributing to dynamics and function, and in influencing treatment outcome. Using thoracic dynamic MRI (dMRI), we have been developing a methodology to overcome this problem. In this paper, we extend this methodology from our previous structural analysis approaches to examining lung tissue properties. We process the T2-weighted dMRI images through a series of steps involving 4D image construction of the acquired dMRI images, intensity non-uniformity correction and standardization of the 4D image, lung segmentation, and estimation of the parameters describing lung tissue intensity distributions in the 4D image. Based on pre- and post-operative dMRI data sets from 25 TIS patients (predominantly neuromuscular and congenital conditions), we demonstrate how lung tissue can be characterized by the estimated distribution parameters. Our results show that standardized T2-weighted image intensity values decrease from the pre- to post-operative condition, likely reflecting improved lung aeration post-operatively. In both pre- and post-operative conditions, the intensity values decrease also from end-expiration to end-inspiration, supporting the basic premise of our results.

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

Hypoxemia, hypercapnia, and breathing pattern in patients with chronic obstructive pulmonary disease.

PubMed

Parot, S; Miara, B; Milic-Emili, J; Gautier, H

1982-11-01

The results of lung function tests (total and functional residual capacities, residual volume/total lung capacity ratio, forced expiratory volume in one second) breathing patterns and arterial PO2 and PCO2 were studied in 651 ambulatory male patients with chronic obstructive pulmonary disease, functionally and clinically stable. Function tests were only loosely correlated with gas tensions: abnormalities in mechanics and in gas exchange are not necessarily related. In patients matched for the degree of obstruction, the breathing pattern depended upon both PaO2 and PaCO2. Isolated hypoxemia was accompanied by increased respiratory frequency without any variation in tidal volume: this suggests that the chemoreceptive systems still responded to changes in PaO2. Isolated hypercapnia was accompanied by a decrease in tidal volume and an increase in respiratory frequency. Consequently, the dead space/tidal volume ratio increased, leading to a drop in alveolar ventilation and to CO2 retention.

Silymarin suppressed lung cancer growth in mice via inhibiting myeloid-derived suppressor cells.

PubMed

Wu, Tiancong; Liu, Wen; Guo, Wenjie; Zhu, Xixu

2016-07-01

In this study, we investigated the antitumor activity of Silymarin in a mouse model of colon cancer xenograft of Lewis lung cancer (LLC) cells. Silymarin significantly suppressed tumor growth and induced apoptosis of cells in tumor tissues at a dose of 25 and 50mg/kg. Silymarin treatment enhanced the infiltration and function of CD8(+) T cells. In the meantime, Silymarin decreased the level of IL-10 while elevated the level of IL-2 and IFN-γ in the serum of tumor-bearing mice. Finally, Silymarin reduced the proportion of myeloid-derived suppressor cells (MDSC) in the tumor tissue and also the mRNA expressions of inducible nitric oxide synthases-2 (iNOS2), arginase-1 (Arg-1) and MMP9, which indicated that the function of MDSC in tumor tissues were suppressed. Altogether, our data here showed that Silymarin inhibited the MDSC and promoted the infiltration and function of CD8(+) T cells thus suppressed the growth of LLC xenografts, which provides evidence for the possible use of Silymarin against lung cancer. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

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. Copyright © 2015 Elsevier B.V. All rights reserved.

lncRNA-HIT promotes cell proliferation of non-small cell lung cancer by association with E2F1.

PubMed

Yu, L; Fang, F; Lu, S; Li, X; Yang, Y; Wang, Z

2017-05-01

Lung cancer is the leading cause of cancer-related death around the world. Long noncoding RNA (lncRNA) has pivotal roles in cancer occurrence and development. However, only a few lncRNAs have been functionally characterized. In the present study, we investigated the effects of lncRNA-HIT (HOXA transcript induced by TGFβ) expression on non-small cell lung cancer (NSCLC) cell phenotype with the gain-of-function and loss-of-function assays. We found that ectopic expression or knockdown of lncRNA-HIT markedly increased or decreased NSCLC cell proliferation, respectively. Moreover, we also showed that lncRNA-HIT interacted with E2F1 to regulate its target genes, such as Survivin, FOXM1, SKP2, NELL2 and DOK1. Collectively, our findings indicated that lncRNA-HIT affected the proliferation of NSCLC cells at least in part via regulating the occupancy of E2F1 in the promoter regions of its target genes. The lncRNA-HIT-E2F1 complex may be a potential target for NSCLC treatment.

Role of glutathione in lung retention of 99mTc-hexamethylpropyleneamine oxime in two unique rat models of hyperoxic lung injury

PubMed Central

Roerig, David L.; Haworth, Steven T.; Clough, Anne V.

2012-01-01

Rat exposure to 60% oxygen (O2) for 7 days (hyper-60) or to >95% O2 for 2 days followed by 24 h in room air (hyper-95R) confers susceptibility or tolerance, respectively, of the otherwise lethal effects of subsequent exposure to 100% O2. The objective of this study was to determine if lung retention of the radiopharmaceutical agent technetium-labeled-hexamethylpropyleneamine oxime (HMPAO) is differentially altered in hyper-60 and hyper-95R rats. Tissue retention of HMPAO is dependent on intracellular content of the antioxidant GSH and mitochondrial function. HMPAO was injected intravenously in anesthetized rats, and planar images were acquired. We investigated the role of GSH in the lung retention of HMPAO by pretreating rats with the GSH-depleting agent diethyl maleate (DEM) prior to imaging. We also measured GSH content and activities of mitochondrial complexes I and IV in lung homogenate. The lung retention of HMPAO increased by ∼50% and ∼250% in hyper-60 and hyper-95R rats, respectively, compared with retention in rats exposed to room air (normoxic). DEM decreased retention in normoxic (∼26%) and hyper-95R (∼56%) rats compared with retention in the absence of DEM. GSH content increased by 19% and 40% in hyper-60 and hyper-95R lung homogenate compared with normoxic lung homogenate. Complex I activity decreased by ∼50% in hyper-60 and hyper-95R lung homogenate compared with activity in normoxic lung homogenate. However, complex IV activity was increased by 32% in hyper-95R lung homogenate only. Furthermore, we identified correlations between the GSH content in lung homogenate and the DEM-sensitive fraction of HMPAO retention and between the complex IV/complex I activity ratio and the DEM-insensitive fraction of HMPAO retention. These results suggest that an increase in the GSH-dependent component of the lung retention of HMPAO may be a marker of tolerance to sustained exposure to hyperoxia. PMID:22628374

Role of glutathione in lung retention of 99mTc-hexamethylpropyleneamine oxime in two unique rat models of hyperoxic lung injury.

PubMed

Audi, Said H; Roerig, David L; Haworth, Steven T; Clough, Anne V

2012-08-15

Rat exposure to 60% oxygen (O(2)) for 7 days (hyper-60) or to >95% O(2) for 2 days followed by 24 h in room air (hyper-95R) confers susceptibility or tolerance, respectively, of the otherwise lethal effects of subsequent exposure to 100% O(2). The objective of this study was to determine if lung retention of the radiopharmaceutical agent technetium-labeled-hexamethylpropyleneamine oxime (HMPAO) is differentially altered in hyper-60 and hyper-95R rats. Tissue retention of HMPAO is dependent on intracellular content of the antioxidant GSH and mitochondrial function. HMPAO was injected intravenously in anesthetized rats, and planar images were acquired. We investigated the role of GSH in the lung retention of HMPAO by pretreating rats with the GSH-depleting agent diethyl maleate (DEM) prior to imaging. We also measured GSH content and activities of mitochondrial complexes I and IV in lung homogenate. The lung retention of HMPAO increased by ≈ 50% and ≈ 250% in hyper-60 and hyper-95R rats, respectively, compared with retention in rats exposed to room air (normoxic). DEM decreased retention in normoxic (≈ 26%) and hyper-95R (≈ 56%) rats compared with retention in the absence of DEM. GSH content increased by 19% and 40% in hyper-60 and hyper-95R lung homogenate compared with normoxic lung homogenate. Complex I activity decreased by ≈ 50% in hyper-60 and hyper-95R lung homogenate compared with activity in normoxic lung homogenate. However, complex IV activity was increased by 32% in hyper-95R lung homogenate only. Furthermore, we identified correlations between the GSH content in lung homogenate and the DEM-sensitive fraction of HMPAO retention and between the complex IV/complex I activity ratio and the DEM-insensitive fraction of HMPAO retention. These results suggest that an increase in the GSH-dependent component of the lung retention of HMPAO may be a marker of tolerance to sustained exposure to hyperoxia.

Novel Flurometric Tool to Assess Mitochondrial Redox State of Isolated Perfused Rat Lungs After Exposure to Hyperoxia

PubMed Central

Audi, Said H.; Staniszewski, Kevin S.; Haworth, Steven T.; Jacobs, Elizabeth R.; Ranji, Mahsa; Zablocki, Clement J.

2013-01-01

Recently, we demonstrated the utility of optical fluorometry to detect a change in the redox status of mitochondrial autofluorescent coenzymes nicotinamide adenine dinucleotide (NADH) and oxidized form of flavin adenine dinucleotide \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}$({\\rm FADH}_{2})$\\end{document} (FAD), as a measure of mitochondrial function in isolated perfused rat lungs (IPL). The objective of this paper was to utilize optical fluorometry to evaluate the effect of rat exposure to hyperoxia (\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}${>}{95\\%}~{\\rm O}_{2}$\\end{document} for 48 h) on lung tissue mitochondrial redox status of NADH and FAD in a nondestructive manner in IPL. Surface NADH and FAD signals were measured before and after lung perfusion with perfusate containing rotenone (ROT, complex I inhibitor), potassium cyanide (KCN, complex IV inhibitor), and/or pentachlorophenol (PCP, uncoupler). ROT- or KCN-induced increase in NADH signal is considered a measure of complex I activity, and KCN-induced decrease in FAD signal is considered a measure of complex II activity. The results show that hyperoxia decreased complex I and II activities by 63% and 55%, respectively, when compared to lungs of rats exposed to room air (normoxic rats). Mitochondrial complex I and II activities in lung homogenates were also lower (77% and 63%, respectively) for hyperoxic than for normoxic lungs. These results suggest that the mitochondrial matrix is more reduced in hyperoxic lungs than in normoxic lungs, and demonstrate the ability of optical fluorometry to detect a change in mitochondrial redox state of hyperoxic lungs prior to histological changes characteristic of hyperoxia. PMID:25379360

Cost and effectiveness of lung lobectomy by video-assisted thoracic surgery for lung cancer

PubMed Central

Mafé, Juan J.; Planelles, Beatriz; Asensio, Santos; Cerezal, Jorge; Inda, María-del-Mar; Lacueva, Javier; Esteban, Maria-Dolores; Hernández, Luis; Martín, Concepción; Baschwitz, Benno

2017-01-01

Background Video-assisted thoracic surgery (VATS) emerged as a minimally invasive surgery for diseases in the field of thoracic surgery. We herein reviewed our experience on thoracoscopic lobectomy for early lung cancer and evaluated Health System use. Methods A cost-effectiveness study was performed comparing VATS vs. open thoracic surgery (OPEN) for lung cancer patients. Demographic data, tumor localization, dynamic pulmonary function tests [forced vital capacity (FVC), forced expiratory volume in one second (FEV1), diffusion capacity (DLCO) and maximal oxygen uptake (VO2max)], surgical approach, postoperative details, and complications were recorded and analyzed. Results One hundred seventeen patients underwent lung resection by VATS (n=42, 36%; age: 63±9 years old, 57% males) or OPEN (n=75, 64%; age: 61±11 years old, 73% males). Pulmonary function tests decreased just after surgery with a parallel increasing tendency during first 12 months. VATS group tended to recover FEV1 and FVC quicker with significantly less clinical and post-surgical complications (31% vs. 53%, P=0.015). Costs including surgery and associated hospital stay, complications and costs in the 12 months after surgery were significantly lower for VATS (P<0.05). Conclusions The VATS approach surgery allowed earlier recovery at a lower cost than OPEN with a better cost-effectiveness profile. PMID:28932560

One-Lung Ventilation with Additional Ipsilateral Ventilation of Low Tidal Volume and High Frequency in Lung Lobectomy

PubMed Central

Feng, Yong; Wang, Jianyue; Zhang, Yang; Wang, Shiduan

2016-01-01

Background To investigate the protective effects of additional ipsilateral ventilation of low tidal volume and high frequency on lung functions in the patients receiving lobectomy. Material/Methods Sixty patients receiving lung lobectomy were randomized into the conventional one-lung ventilation (CV) group (n=30) and the ipsilateral low tidal volume high frequency ventilation (LV) group (n=30). In the CV group, patients received only contralateral OLV. In the LV group, patients received contralateral ventilation and additional ipsilateral ventilation of low tidal volume of 1–2 ml/kg and high frequency of 40 times/min. Normal lung tissues were biopsied for the analysis of lung injury. Lung injury was scored by evaluating interstitial edema, alveolar edema, neutrophil infiltration, and alveolar congestion. Results At 30 min and 60 min after the initiation of one-lung ventilation and after surgery, patients in the LV group showed significantly higher ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen than those in the CV group (P<0.001). Lung injury was significantly less severe (2.7±0.7) in the LV group than in the CV group (3.1±0.7) (P=0.006). Conclusions Additional ipsilateral ventilation of low tidal volume and high frequency can decrease the risk of hypoxemia and alleviate lung injury in patients receiving lobectomy. PMID:27166086

Effects of side lying on lung function in older individuals.

PubMed

Manning, F; Dean, E; Ross, J; Abboud, R T

1999-05-01

Body positioning exerts a strong effect on pulmonary function, but its effect on other components of the oxygen transport pathway are less well understood, especially the effects of side-lying positions. This study investigated the interrelationships between side-lying positions and indexes of lung function such as spirometry, alveolar diffusing capacity, and inhomogeneity of ventilation in older individuals. Nineteen nonsmoking subjects (mean age=62.8 years, SD=6.8, range=50-74) with no history of cardiac or pulmonary disease were tested over 2 sessions. The test positions were sitting and left side lying in one session and sitting and right side lying in the other session. In each of the positions, forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), single-breath pulmonary diffusing capacity (DLCO/VA), and the slope of phase III (DN2%/L) of the single-breath nitrogen washout test to determine inhomogeneity of ventilation were measured. Compared with measurements obtained in the sitting position, FVC and FEV1 were decreased equally in the side-lying positions, but no change was observed in DLCO/VA or DN2%/L. Side-lying positions resulted in decreases in FVC and FEV1, which is consistent with the well-documented effects of the supine position. These findings further support the need for prescriptive rather than routine body positioning of patients with risks of cardiopulmonary compromise and the need to use upright positions in which lung volumes and capacities are maximized.

Impact of Geocoding Methods on Associations between Long-term Exposure to Urban Air Pollution and Lung Function

PubMed Central

Jacquemin, Bénédicte; Lepeule, Johanna; Boudier, Anne; Arnould, Caroline; Benmerad, Meriem; Chappaz, Claire; Ferran, Joane; Kauffmann, Francine; Morelli, Xavier; Pin, Isabelle; Pison, Christophe; Rios, Isabelle; Temam, Sofia; Künzli, Nino; Slama, Rémy

2013-01-01

Background: Errors in address geocodes may affect estimates of the effects of air pollution on health. Objective: We investigated the impact of four geocoding techniques on the association between urban air pollution estimated with a fine-scale (10 m × 10 m) dispersion model and lung function in adults. Methods: We measured forced expiratory volume in 1 sec (FEV1) and forced vital capacity (FVC) in 354 adult residents of Grenoble, France, who were participants in two well-characterized studies, the Epidemiological Study on the Genetics and Environment on Asthma (EGEA) and the European Community Respiratory Health Survey (ECRHS). Home addresses were geocoded using individual building matching as the reference approach and three spatial interpolation approaches. We used a dispersion model to estimate mean PM10 and nitrogen dioxide concentrations at each participant’s address during the 12 months preceding their lung function measurements. Associations between exposures and lung function parameters were adjusted for individual confounders and same-day exposure to air pollutants. The geocoding techniques were compared with regard to geographical distances between coordinates, exposure estimates, and associations between the estimated exposures and health effects. Results: Median distances between coordinates estimated using the building matching and the three interpolation techniques were 26.4, 27.9, and 35.6 m. Compared with exposure estimates based on building matching, PM10 concentrations based on the three interpolation techniques tended to be overestimated. When building matching was used to estimate exposures, a one-interquartile range increase in PM10 (3.0 μg/m3) was associated with a 3.72-point decrease in FVC% predicted (95% CI: –0.56, –6.88) and a 3.86-point decrease in FEV1% predicted (95% CI: –0.14, –3.24). The magnitude of associations decreased when other geocoding approaches were used [e.g., for FVC% predicted –2.81 (95% CI: –0.26, –5.35) using NavTEQ, or 2.08 (95% CI –4.63, 0.47, p = 0.11) using Google Maps]. Conclusions: Our findings suggest that the choice of geocoding technique may influence estimated health effects when air pollution exposures are estimated using a fine-scale exposure model. Citation: Jacquemin B, Lepeule J, Boudier A, Arnould C, Benmerad M, Chappaz C, Ferran J, Kauffmann F, Morelli X, Pin I, Pison C, Rios I, Temam S, Künzli N, Slama R, Siroux V. 2013. Impact of geocoding methods on associations between long-term exposure to urban air pollution and lung function. Environ Health Perspect 121:1054–1060; http://dx.doi.org/10.1289/ehp.1206016 PMID:23823697

The regulation of inflammation and oxidative status against lung injury of residue polysaccharides by Lentinula edodes.

PubMed

Ren, Zhenzhen; Li, Juan; Song, Xinling; Zhang, Jianjun; Wang, Wenshuai; Wang, Xiuxiu; Gao, Zheng; Jing, Huijuan; Li, Shangshang; Jia, Le

2018-01-01

In present study, two hydrolyzed residue polysaccharides (RPS) of enzymatic-RPS (ERPS) and acidic-RPS (ARPS) were successfully obtained from the residue of Lentinula edodes, and the anti-inflammatory as well as antioxidative effects on lipopolysaccharide-induced (LPS-induced) lung injured mice were investigated. The results demonstrated that ERPS showed superior lung protective effects by ameliorating the lung wet-to-dry weight (W/D) ratio, reducing the TNF-α, IL-6, and IL-1β levels in BALF, lowing the pulmonary MPO activity, decreasing the serum C3 and hs-CPR contents, as well as improving the antioxidant status by enhancing pulmonary enzyme activities (SOD, GSH-Px, CAT, and T-AOC) and eliminating the lipid peroxidation (MDA and LPO), respectively. These conclusions indicated that both RPS and its hydrolysates (ARPS and ERPS) might be suitable for functional foods and a potentially effective candidate medicine for the treatment of lung injury. Copyright © 2017 Elsevier B.V. All rights reserved.

Activation of the PD-1 pathway contributes to immune escape in EGFR-driven lung tumors

PubMed Central

Akbay, Esra A; Koyama, Shohei; Carretero, Julian; Altabef, Abigail; Tchaicha, Jeremy H; Christensen, Camilla L; Mikse, Oliver R; Cherniack, Andrew D; Beauchamp, Ellen M; Pugh, Trevor J; Wilkerson, Matthew D; Fecci, Peter E; Butaney, Mohit; Reibel, Jacob B; Soucheray, Margaret; Cohoon, Travis J; Janne, Pasi A; Meyerson, Matthew; Hayes, D. Neil; Shapiro, Geoffrey I; Shimamura, Takeshi; Sholl, Lynette M; Rodig, Scott J; Freeman, Gordon J; Hammerman, Peter S; Dranoff, Glenn; Wong, Kwok-Kin

2013-01-01

The success in lung cancer therapy with Programmed Death (PD)-1 blockade suggests that immune escape mechanisms contribute to lung tumor pathogenesis. We identified a correlation between Epidermal Growth Factor Receptor (EGFR) pathway activation and a signature of immunosuppression manifested by upregulation of PD-1, PD-L1, cytotoxic T lymphocyte antigen-4 (CTLA-4), and multiple tumor-promoting inflammatory cytokines. We observed decreased cytotoxic T cells and increased markers of T cell exhaustion in mouse models of EGFR-driven lung cancer. PD-1 antibody blockade improved the survival of mice with EGFR-driven adenocarcinomas by enhancing effector T cell function and lowering the levels of tumor-promoting cytokines. Expression of mutant EGFR in bronchial epithelial cells induced PD-L1, and PD-L1 expression was reduced by EGFR inhibitors in non-small cell lung cancer cell lines with activated EGFR. These data suggest that oncogenic EGFR signaling remodels the tumor microenvironment to trigger immune escape, and mechanistically link treatment response to PD-1 inhibition. PMID:24078774

HEALTH EFFECTS OF REAL-WORLD EXPOSURE TO DIESEL EXHAUST IN PERSONS WITH ASTHMA

EPA Science Inventory

Investigators anticipate that this proposed research will indicate that lung function is slightly decreased and some markers of airway inflammation are increased in people with asthma who are exposed to ambient urban air in a roadside environment dominated by diesel vehicle...

Peripheral 5-HT7 receptors as a new target for prevention of lung injury and mortality in septic rats.

PubMed

Cadirci, Elif; Halici, Zekai; Bayir, Yasin; Albayrak, Abdulmecit; Karakus, Emre; Polat, Beyzagul; Unal, Deniz; Atamanalp, Sabri S; Aksak, Selina; Gundogdu, Cemal

2013-10-01

Sepsis is a complex pathophysiological event involving metabolic acidosis, systemic inflammatory response syndrome, tissue damage and multiple organ dysfunction syndrome. Although many new mechanisms are being investigated to enlighten the pathophysiology of sepsis, there is no effective treatment protocol yet. Presence of 5-HT7 receptors in immune tissues prompted us to hypothesize that these receptors have roles in inflammation and sepsis. We investigated the effects of 5-HT7 receptor agonists and antagonists on serum cytokine levels, lung oxidative stress, lung histopathology, nuclear factor κB (NF-κB) positivity and lung 5-HT7 receptor density in cecal ligation and puncture (CLP) induced sepsis model of rats. Agonist administration to septic rats increased survival time; decreased serum cytokine response against CLP; decreased oxidative stress and increased antioxidant system in lungs; decreased the tissue NF-κB immunopositivity, which is high in septic rats; and decreased the sepsis-induced lung injury. In septic rats, as a result of high inflammatory response, 5-HT7 receptor expression in lungs increased significantly and agonist administration, which decreased inflammatory response and related mortality, decreased the 5-HT7 receptor expression. In conclusion, all these data suggest that stimulation of 5-HT7 receptors may be a new therapeutic target for prevention of impaired inflammatory response related lung injury and mortality. Copyright © 2013 Elsevier GmbH. All rights reserved.

Longitudinal Lung Function Decrease in Subjects with Spontaneous Healed Pulmonary Tuberculosis.

PubMed

Lee, Seung Heon; Kwon, Amy M; Yang, Hae-Chung; Lee, Seung Ku; Kim, Young; Choi, Jong Hyun; Kim, Je Hyeong; Shin, Chol

2016-01-01

We compared the longitudinal course of post-bronchodilator Forced Expiratory Volume in 1 second (pFEV1) over a 10-year period in subjects with spontaneous healed pulmonary tuberculosis (SHPTB) with that in normal subjects. We prospectively investigated 339 subjects with SHPTB and 3211 normal subjects. pFEV1 values measured biannually over 10 years were analyzed using mixed effects model. At baseline, there were no differences in gender, smoking amount, and mean height, except mean age (50.0 ± 8.1 VS. 48.1 ± 7.3, P< 0.001) between the SHPTB and normal group. 52% of the 339 participants with SHPTB and 56% of the 3211 normal participants participated till the end of study. According to the final model, the SHPTB group showed significantly larger decrease in the average pFEV1 over the time than the normal group (P< 0.001) adjusted for gender, age, height, smoking pack years, and time effects. Especially, the interaction effect between time and group was statistically significant (P = 0.036). The average lung function in terms of pFEV1 decreases faster in subjects with SHPTB than in normal individuals over time.

Diesel exhaust particle promotes tumor lung metastasis via the induction of BLT1-mediated neutrophilic lung inflammation.

PubMed

Li, Wenjing; Liu, Ting; Xiong, Yingluo; Lv, Jiaoyan; Cui, Xinyi; He, Rui

2018-06-05

BLT1, the primary functional receptor of Leukotriene B4 (LTB4), is involved in tissue inflammation by mediating leukocyte recruitment, and recently LTB4-dependent inflammation was reported to promote lung tumor growth. Exposure to diesel exhaust particle (DEP), the major component of particulate matter 2.5 (PM 2.5 ), can elicit lung inflammation, which may increase the risk of lung cancer. However, it remains unknown about the critical factors mediating DEP-induced lung inflammation and the subsequent effect on tumor metastasis. In this study, we found that DEP exposure led to acute lung inflammation, characterized by abundant infiltration of neutrophils and elevated lung levels in LTB4, as well as several pro-inflammatory cytokines and chemokines, including IL-1β, IL-6, TNF-α, CXCL1/2. Furthermore, DEP exposure promoted lung metastasis of 3LL and 4T1 cells. BLT1 blockade by its specific antagonist U75302 significantly inhibited neutrophilic lung inflammation following DEP exposure. Importantly, BLT1 blockade before the onset of inflammation significantly reduced DEP-enhanced lung metastasis, which was associated with greatly decreased infiltrating neutrophils in lungs. Interestingly, BLT1 blockade after the occurrence of lung metastases had no effect on the magnitude of lung metastasis, suggesting that inhibition of BLT1-mediated lung inflammation was insufficient to suppress established metastatic tumor. Administration of BLT2 inhibitor LY255283 fails to inhibit DEP-induced lung inflammation and tumor metastasis. Collectively, our results demonstrate that DEP exposure causes BLT1-mediated lung neutrophilic inflammation, which is critical for tumor lung metastasis, and suggest that interruption of the LTB4-BLT1 axis could be useful for preventing PM 2.5 -induced inflammation and subsequent susceptible to lung metastasis. Copyright © 2018 Elsevier Ltd. All rights reserved.

miR-138 suppresses the proliferation, metastasis and autophagy of non-small cell lung cancer by targeting Sirt1.

PubMed

Ye, Zaiting; Fang, Bingmu; Pan, Jiongwei; Zhang, Ning; Huang, Jinwei; Xie, Congying; Lou, Tianzheng; Cao, Zhuo

2017-06-01

The present study determined the role and mechanism of miR-138 in non-small cell lung cancer (NSCLC). In total, 45 freshly resected clinical NSCLC tissues were collected. The expression of miR-138 in tissues and cell lines were determined by real-time quantitative PCR. miR-138 mimics were transfected into A549 and Calu-3 cells in vitro, and then the effects of miR-138 on lung cancer cell proliferation, cell cycle, invasion and metastasis were investigated by CCK-8 assay, Transwell and flow cytometry, respectively. The protein expression of the potential target gene Sirt1 in lung cancer cells were determined by western blot analysis. Dual-luciferase reporter assay was performed to further confirm whether Sirt1 was the target gene of miR-138. The expression of miR-138 was significantly lower in lung cancer tissues and was negatively correlated to the differentiation degree and lymph node metastasis of lung cancer. In vitro experiment results showed that miR-138 inhibited lung cancer cell proliferation, invasion and migration. It was verified that miR-138 could downregulate Sirt1 protein expression, inhibit epithelial-mesenchymal transition (EMT), decrease the activity of AMPK signaling pathway and elevate mTOR phosphorylation level. Dual-luciferase reporter assay demonstrated that miR-138 could directly regulate Sirt1. Downregulation of Sirt1 alone can also cause the same molecular and biological function changes. Western blot analysis and confocal microscopy results indicated that overexpression of miR-138 or interference of Sirt1 expression could inhibit lung cancer cell autophagy activity possibly through AMPK-mTOR signaling pathway. miR-138 plays a tumor suppressor function in lung cancer. It may inhibit the proliferation, invasion and migration of lung cancer through downregulation of Sirt1 expression and activation of cell autophagy. The downregulation of miR-138 is closely related to the development of lung cancer.

Physiological gas exchange mapping of hyperpolarized 129 Xe using spiral-IDEAL and MOXE in a model of regional radiation-induced lung injury.

PubMed

Zanette, Brandon; Stirrat, Elaine; Jelveh, Salomeh; Hope, Andrew; Santyr, Giles

2018-02-01

To map physiological gas exchange parameters using dissolved hyperpolarized (HP) 129 Xe in a rat model of regional radiation-induced lung injury (RILI) with spiral-IDEAL and the model of xenon exchange (MOXE). Results are compared to quantitative histology of pulmonary tissue and red blood cell (RBC) distribution. Two cohorts (n = 6 each) of age-matched rats were used. One was irradiated in the right-medial lung, producing regional injury. Gas exchange was mapped 4 weeks postirradiation by imaging dissolved-phase HP 129 Xe using spiral-IDEAL at five gas exchange timepoints using a clinical 1.5 T scanner. Physiological lung parameters were extracted regionally on a voxel-wise basis using MOXE. Mean gas exchange parameters, specifically air-capillary barrier thickness (δ) and hematocrit (HCT) in the right-medial lung were compared to the contralateral lung as well as nonirradiated control animals. Whole-lung spectroscopic analysis of gas exchange was also performed. δ was significantly increased (1.43 ± 0.12 μm from 1.07 ± 0.09 μm) and HCT was significantly decreased (17.2 ± 1.2% from 23.6 ± 1.9%) in the right-medial lung (i.e., irradiated region) compared to the contralateral lung of the irradiated rats. These changes were not observed in healthy controls. δ and HCT correlated with histologically measured increases in pulmonary tissue heterogeneity (r = 0.77) and decreases in RBC distribution (r = 0.91), respectively. No changes were observed using whole-lung analysis. This work demonstrates the feasibility of mapping gas exchange using HP 129 Xe in an animal model of RILI 4 weeks postirradiation. Spatially resolved gas exchange mapping is sensitive to regional injury between cohorts that was undetected with whole-lung gas exchange analysis, in agreement with histology. Gas exchange mapping holds promise for assessing regional lung function in RILI and other pulmonary diseases. © 2017 The Authors. Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

Reactive oxygen species produced by NADPH oxidase and mitochondrial dysfunction in lung after an acute exposure to Residual Oil Fly Ashes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Magnani, Natalia D.; Marchini, Timoteo; Vanasco, Virginia

2013-07-01

Reactive O{sub 2} species production triggered by particulate matter (PM) exposure is able to initiate oxidative damage mechanisms, which are postulated as responsible for increased morbidity along with the aggravation of respiratory diseases. The aim of this work was to quantitatively analyse the major sources of reactive O{sub 2} species involved in lung O{sub 2} metabolism after an acute exposure to Residual Oil Fly Ashes (ROFAs). Mice were intranasally instilled with a ROFA suspension (1.0 mg/kg body weight), and lung samples were analysed 1 h after instillation. Tissue O{sub 2} consumption and NADPH oxidase (Nox) activity were evaluated in tissuemore » homogenates. Mitochondrial respiration, respiratory chain complexes activity, H{sub 2}O{sub 2} and ATP production rates, mitochondrial membrane potential and oxidative damage markers were assessed in isolated mitochondria. ROFA exposure was found to be associated with 61% increased tissue O{sub 2} consumption, a 30% increase in Nox activity, a 33% increased state 3 mitochondrial O{sub 2} consumption and a mitochondrial complex II activity increased by 25%. During mitochondrial active respiration, mitochondrial depolarization and a 53% decreased ATP production rate were observed. Neither changes in H{sub 2}O{sub 2} production rate, nor oxidative damage in isolated mitochondria were observed after the instillation. After an acute ROFA exposure, increased tissue O{sub 2} consumption may account for an augmented Nox activity, causing an increased O{sub 2}{sup ·−} production. The mitochondrial function modifications found may prevent oxidative damage within the organelle. These findings provide new insights to the understanding of the mechanisms involving reactive O{sub 2} species production in the lung triggered by ROFA exposure. - Highlights: • Exposure to ROFA alters the oxidative metabolism in mice lung. • The augmented Nox activity contributes to the high tissue O{sub 2} consumption. • Exposure to ROFA produces alterations in mitochondrial function. • ΔΨ{sub m} decrease in state 3 may be responsible for the decreased ATP production. • Mild uncoupling prevents mitochondrial oxidative damage.« less

Isolated Human Pulmonary Artery Structure and Function Pre- and Post-Cardiopulmonary Bypass Surgery.

PubMed

Dora, Kim A; Stanley, Christopher P; Al Jaaly, Emad; Fiorentino, Francesca; Ascione, Raimondo; Reeves, Barnaby C; Angelini, Gianni D

2016-02-23

Pulmonary dysfunction is a known complication after cardiac surgery using cardiopulmonary bypass, ranging from subclinical functional changes to prolonged postoperative ventilation, acute lung injury, and acute respiratory distress syndrome. Whether human pulmonary arterial function is compromised is unknown. The aim of the present study was to compare the structure and function of isolated and cannulated human pulmonary arteries obtained from lung biopsies after the chest was opened (pre-cardiopulmonary bypass) to those obtained at the end of cardiopulmonary bypass (post-cardiopulmonary bypass) from patients undergoing coronary artery bypass graft surgery. Pre- and post-cardiopulmonary bypass lung biopsies were received from 12 patients undergoing elective surgery. Intralobular small arteries were dissected, cannulated, pressurized, and imaged using confocal microscopy. Functionally, the thromboxane mimetic U46619 produced concentration-dependent vasoconstriction in 100% and 75% of pre- and post-cardiopulmonary bypass arteries, respectively. The endothelium-dependent agonist bradykinin stimulated vasodilation in 45% and 33% of arteries pre- and post-cardiopulmonary bypass, respectively. Structurally, in most arteries smooth muscle cells aligned circumferentially; live cell viability revealed that although 100% of smooth muscle and 90% of endothelial cells from pre-cardiopulmonary bypass biopsies had intact membranes and were considered viable, only 60% and 58%, respectively, were viable from post-cardiopulmonary bypass biopsies. We successfully investigated isolated pulmonary artery structure and function in fresh lung biopsies from patients undergoing heart surgery. Pulmonary artery contractile tone and endothelium-dependent dilation were significantly reduced in post-cardiopulmonary bypass biopsies. The decreased functional responses were associated with reduced cell viability. URL: http://www.isrctn.com/ISRCTN34428459. Unique identifier: ISRCTN 34428459. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Astilbin alleviates sepsis-induced acute lung injury by inhibiting the expression of macrophage inhibitory factor in rats.

PubMed

Zhang, Hong-Bo; Sun, Li-Chao; Zhi, Li-da; Wen, Qian-Kuan; Qi, Zhi-Wei; Yan, Sheng-Tao; Li, Wen; Zhang, Guo-Qiang

2017-10-01

Sepsis is a systemic inflammatory response syndrome caused by severe infections. Astilbin is a dihydroflavonol derivative found in many medicinal and food plants with multiple pharmacological functions. To investigate the effects of astilbin on sepsis-induced acute lung injury (ALI), cecal ligation and puncture was performed on rats to establish a sepsis-induced ALI model; these rats were then treated with astilbin at different concentrations. Lung injury scores, including lung wet/dry ratio, protein leakage, myeloperoxidase activity, and inflammatory cell infiltration were determined to evaluate the effects of astilbin on sepsis-induced ALI. We found that astilbin treatment significantly attenuates sepsis-induced lung injury and improves survival rate, lung injury scores, lung wet/dry ratio, protein leakage, myeloperoxidase activity, and inflammatory cell infiltration. Astilbin treatment also dramatically decreased the production of inflammatory cytokines and chemokines in bronchoalveolar lavage fluid. Further, astilbin treatment inhibited the expression and production of macrophage inhibitory factor (MIF), which inhibits the inflammatory response. Collectively, these data suggest that astilbin has a protective effect against sepsis-induced ALI by inhibiting MIF-mediated inflammatory responses. This study provides a molecular basis for astilbin as a new medical treatment for sepsis-induced ALI.

Characterization of the seven-day course of pulmonary response following unilateral lung acid injury in rats.

PubMed

Setzer, Florian; Schmidt, Barbara; Hueter, Lars; Schwarzkopf, Konrad; Sänger, Jörg; Schreiber, Torsten

2018-01-01

Aspiration of gastric acid is an important cause of acute lung injury. The time course of the pulmonary response to such an insult beyond the initial 48 hours is incompletely characterized. The purpose of this study was to comprehensively describe the pulmonary effects of focal lung acid injury over a seven day period in both directly injured and not directly injured lung tissue. Male Wistar rats underwent left-endobronchial instillation with hydrochloric acid and were sacrificed at 4, 24, 48, 96 or 168 h after the insult. Healthy non-injured animals served as controls. We assessed inflammatory cell counts and cytokine levels in right and left lung lavage fluid and blood, arterial oxygen tension, alterations in lung histology, lung wet-to-dry weight ratio and differential lung perfusion. Lung acid instillation induced an early strong inflammatory response in the directly affected lung, peaking at 4-24 hours, with only partial resolution after 7 days. A less severe response with complete resolution after 4 days was seen in the opposite lung. Alveolar cytokine levels, with exception of IL-6, only partially reflected the localization of lung injury and the time course of the functional and histologic alterations. Alveolar leucocyte subpopulations exhibited different time courses in the acid injured lung with persistent elevation of alveolar lymphocytes and macrophages. After acid instillation there was an early transient decrease in arterial oxygen tension and lung perfusion was preferentially distributed to the non-injured lung. These findings provide a basis for further research in the field of lung acid injury and for studies exploring effects of mechanical ventilation on injured lungs. Incomplete recovery in the directly injured lung 7 days after acid instillation suggests that increased vulnerability and susceptibility to further noxious stimuli are still present at that time.

[Impaired lung function in patients with moderate chronic obstructive bronchitis].

PubMed

Nefedov, V B; Popova, L A; Shergina, E A

2004-01-01

VC, FVC, FEV1, FEV1/VC%, PEF, MEF25, MEF50, MEF75, TLC, TGV, RV, Raw, Rin, Rex, DLCO-SS, paO2 and paCO2 were determined in 22 patients with moderate chronic obstructive bronchitis (FEV1, 79-50% of the normal value). All the patients were found to have impaired bronchial patency, 90.9% of the patients had lung volume and capacity changes; pulmonary gas exchange dysfunction was present in 72.7%. Bronchial patency impairments were manifested by a decrease in FEV1, FEV1/VC%, PEF, MEF25, MEF50, MEF75, and an increase in Raw, Rin, Rex. Changes in the lung volumes and capacities appeared as higher RV, TGV, TLC, lower VC and FVC. Pulmonary gas exchange dysfunction showed up as a reduction in pO2 and DLCO-SS a reduction and an increase in paCO2. The magnitude of the functional changes observed in most patients was low. Significant and pronounced disorders were seen in one third of the patients.

Creation of Lung-Targeted Dexamethasone Immunoliposome and Its Therapeutic Effect on Bleomycin-Induced Lung Injury in Rats

PubMed Central

Li, Nan; Hu, Yang; Zhang, Yuan; Xu, Jin-Fu; Li, Xia; Ren, Jie; Su, Bo; Yuan, Wei-Zhong; Teng, Xin-Rong; Zhang, Rong-Xuan; Jiang, Dian-hua; Mulet, Xavier; Li, Hui-Ping

2013-01-01

Objective Acute lung injury (ALI), is a major cause of morbidity and mortality, which is routinely treated with the administration of systemic glucocorticoids. The current study investigated the distribution and therapeutic effect of a dexamethasone(DXM)-loaded immunoliposome (NLP) functionalized with pulmonary surfactant protein A (SP-A) antibody (SPA-DXM-NLP) in an animal model. Methods DXM-NLP was prepared using film dispersion combined with extrusion techniques. SP-A antibody was used as the lung targeting agent. Tissue distribution of SPA-DXM-NLP was investigated in liver, spleen, kidney and lung tissue. The efficacy of SPA-DXM-NLP against lung injury was assessed in a rat model of bleomycin-induced acute lung injury. Results The SPA-DXM-NLP complex was successfully synthesized and the particles were stable at 4°C. Pulmonary dexamethasone levels were 40 times higher with SPA-DXM-NLP than conventional dexamethasone injection. Administration of SPA-DXM-NLP significantly attenuated lung injury and inflammation, decreased incidence of infection, and increased survival in animal models. Conclusions The administration of SPA-DXM-NLP to animal models resulted in increased levels of DXM in the lungs, indicating active targeting. The efficacy against ALI of the immunoliposomes was shown to be superior to conventional dexamethasone administration. These results demonstrate the potential of actively targeted glucocorticoid therapy in the treatment of lung disease in clinical practice. PMID:23516459

Differential Effects of Particulate Matter Upwind and Downwind of an Urban Freeway in an Allergic Mouse Model

EPA Science Inventory

Near-road exposure to air pollutants has been associated with decreased lung function and other adverse health effects in susceptible populations. This study was designed to investigate whether different types of near-road particulate matter (PM) contribute to exacerbation of all...

77 FR 40149 - Approval, Disapproval and Promulgation of Implementation Plans; State of Nebraska; Regional Haze...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-06

... portion of Nebraska's regional haze plan for the first implementation period (through 2018), and proposing... respiratory diseases, asthma attacks, and decreased lung function. In addition, NO X reacts with ammonia, moisture, and other compounds to form particulates that can cause and worsen respiratory diseases...

Atopic asthmatic subjects but not atopic subjects without asthma have enhanced inflammatory response to ozone

EPA Science Inventory

BACKGROUND: Asthma is a known risk factor for acute ozone-associated respiratory disease. Ozone causes an immediate decrease in lung function and increased airway inflammation. The role of atopy and asthma in modulation of ozone-induced inflammation has not been determined. OB...

Aptopic asthmatic subjects but not aptopic subjects without asthma have enhanced inflammatory response to ozone**

EPA Science Inventory

Background Asthma is a known risk factor for acute ozone-associated respiratory disease. Ozone (03) causes an immediate decrease in lung function and increased airway inflammation. The role of atopy and asthma in modulation of 03-induced inflammation has not been determined. Ob...

The glutathione-S-transferase Mu 1 null genotype modulates ozone-induced airway inflammation in humans*

EPA Science Inventory

Background: The Glutathione-S-Transferase Mu 1 null genotype has been reported to be a risk factor for acute respiratory disease associated with increases in ambient air ozone. Ozone is known to cause an immediate decrease in lung function and increased airway inflammation. Howev...

Pathobiological implications of MUC4 in non-small-cell lung cancer.

PubMed

Majhi, Prabin Dhangada; Lakshmanan, Imayavaramban; Ponnusamy, Moorthy P; Jain, Maneesh; Das, Srustidhar; Kaur, Sukhwinder; Shimizu, Su Tomohiro; West, William W; Johansson, Sonny L; Smith, Lynette M; Yu, Fang; Rolle, Cleo E; Sharma, Poonam; Carey, George B; Batra, Surinder K; Ganti, Apar Kishor

2013-04-01

Altered expression of MUC4 plays an oncogenic role in various cancers, including pancreatic, ovarian, and breast. This study evaluates the expression and role of MUC4 in non-small-cell lung cancer (NSCLC). We used a paired system of MUC4-expressing (H292) and MUC4-nonexpressing (A549) NSCLC cell lines to analyze MUC4-dependent changes in growth rate, migration, and invasion using these sublines. We also evaluated the alterations of several tumor suppressor, proliferation, and metastasis markers with altered MUC4 expression. Furthermore, the association of MUC4 expression (by immunohistochemistry) in lung cancer samples with patient survival was evaluated. MUC4-expressing lung cancer cells demonstrated a less proliferative and metastatic phenotype. Up-regulation of p53 in MUC4-expressing lung cancer cells led to the accumulation of cells at the G2/M phase of cell cycle progression. MUC4 expression attenuated Akt activation and decreased the expression of Cyclins D1 and E, but increased the expression of p21 and p27. MUC4 expression abrogated cancer cell migration and invasion by altering N- & E-cadherin expression and FAK phosphorylation. A decrease in MUC4 expression was observed with increasing tumor stage (mean composite score: stage I, 2.4; stage II, 1.8; stage III, 1.4; and metastatic, 1.2; p = 0.0093). Maximal MUC4 expression was associated with a better overall survival (p = 0.042). MUC4 plays a tumor-suppressor role in NSCLC by altering p53 expression in NSCLC. Decrease in MUC4 expression in advanced tumor stages also seems to confirm the novel protective function of MUC4 in NSCLC.

Single-dose rosuvastatin ameliorates lung ischemia-reperfusion injury via upregulation of endothelial nitric oxide synthase and inhibition of macrophage infiltration in rats with pulmonary hypertension.

PubMed

Matsuo, Satoshi; Saiki, Yuriko; Adachi, Osamu; Kawamoto, Shunsuke; Fukushige, Shinichi; Horii, Akira; Saiki, Yoshikatsu

2015-03-01

Lung ischemia-reperfusion (IR) injury during cardiopulmonary surgery is associated with postoperative morbidity and mortality, particularly in patients with pulmonary hypertension (PH). Using a rat model for monocrotaline-induced PH, we investigated the protective effect of rosuvastatin against IR injury in lungs affected by PH and attempted to elucidate its mechanism of action. Male Sprague-Dawley monocrotaline-treated rats were divided into 4 groups (n = 8-9): sham, control + IR, statin + IR, and statin + mevalonolactone + IR. Lung ischemia was induced by left pulmonary artery occlusion (1 hour), followed by reperfusion (4 hours). Rosuvastatin (2 mg/kg) was injected 18 hours before reperfusion and mevalonolactone (1 mg/kg) was injected immediately before reperfusion. The arterial oxygen tension/inspired oxygen fraction ratio was used as a measure of lung oxygenation. Left lung tissue was analyzed for the wet-to-dry lung weight ratio and protein expression of endothelial nitric oxide synthase (eNOS) and phospho-eNOS. Macrophage recruitment was assessed by CD68 immunostaining. Our results showed that rosuvastatin decreased IR lung injury (control + IR vs statin + IR) in terms of the arterial oxygen tension/inspired oxygen fraction ratio (272 ± 43 vs 442 ± 13), wet-to-dry ratio (5.7 ± 0.7 vs 4.8 ± 0.6), and macrophage infiltration (8.0 ± 0.6/field vs 4.0 ± 0.5/field) (P < .05 for all). eNOS and phospho-eNOS were downregulated by IR, which was blocked by rosuvastatin. Effects of rosuvastatin were blunted by mevalonolactone. Single-dose rosuvastatin decreased IR injury in lungs affected by PH via 2 anti-inflammatory mechanisms: preserving eNOS function and inhibiting macrophage infiltration. Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Physical complications in acute lung injury survivors: a two-year longitudinal prospective study.

PubMed

Fan, Eddy; Dowdy, David W; Colantuoni, Elizabeth; Mendez-Tellez, Pedro A; Sevransky, Jonathan E; Shanholtz, Carl; Himmelfarb, Cheryl R Dennison; Desai, Sanjay V; Ciesla, Nancy; Herridge, Margaret S; Pronovost, Peter J; Needham, Dale M

2014-04-01

Survivors of severe critical illness frequently develop substantial and persistent physical complications, including muscle weakness, impaired physical function, and decreased health-related quality of life. Our objective was to determine the longitudinal epidemiology of muscle weakness, physical function, and health-related quality of life and their associations with critical illness and ICU exposures. A multisite prospective study with longitudinal follow-up at 3, 6, 12, and 24 months after acute lung injury. Thirteen ICUs from four academic teaching hospitals. Two hundred twenty-two survivors of acute lung injury. None. At each time point, patients underwent standardized clinical evaluations of extremity, hand grip, and respiratory muscle strength; anthropometrics (height, weight, mid-arm circumference, and triceps skin fold thickness); 6-minute walk distance, and the Medical Outcomes Short-Form 36 health-related quality of life survey. During their hospitalization, survivors also had detailed daily evaluation of critical illness and related treatment variables. Over one third of survivors had objective evidence of muscle weakness at hospital discharge, with most improving within 12 months. This weakness was associated with substantial impairments in physical function and health-related quality of life that persisted at 24 months. The duration of bed rest during critical illness was consistently associated with weakness throughout 24-month follow-up. The cumulative dose of systematic corticosteroids and use of neuromuscular blockers in the ICU were not associated with weakness. Muscle weakness is common after acute lung injury, usually recovering within 12 months. This weakness is associated with substantial impairments in physical function and health-related quality of life that continue beyond 24 months. These results provide valuable prognostic information regarding physical recovery after acute lung injury. Evidence-based methods to reduce the duration of bed rest during critical illness may be important for improving these long-term impairments.

CPAP of 4 cm H(2)O Has no short-term benefit at term in infants with BPD.

PubMed

Sandberg, Kenneth L; Hjalmarson, Ola

2012-01-01

Lung development and function is compromised at term in infants with bronchopulmonary dysplasia (BPD), characterized by reduced functional residual capacity (FRC) and impaired gas-mixing efficiency in distal airways. To determine whether continuous positive airway pressure (CPAP) improves FRC, ventilation, distal airway function, and gas exchange in spontaneously breathing infants with BPD. Twenty-one infants with BPD (median birth weight 0.72 kg (range 0.50-1.27) and median gestational age 26 weeks (range 23-28)) were studied before and after CPAP of 4 cm H(2)O was applied by a facemask system. A multiple-breath nitrogen washout method was used to assess FRC, ventilation, and gas-mixing efficiency. Moment analysis and lung clearance index was calculated from the nitrogen-decay curve for assessment of gas-mixing efficiency. Transcutaneous (Tc) PO(2)/PCO(2) was monitored during stable infant conditions before each washout test. When CPAP was raised from 0 to 4 cm H(2)O, FRC increased significantly together with a significant increase in moment ratios (M(1)/M(0) and M(2)/M(0)). Tc PO(2) decreased significantly and the breathing pattern changed, with significantly reduced respiratory rate, minute ventilation, and alveolar ventilation. There was also an increase in tidal volume and dead space. CPAP of 4 cm H(2)O applied with a facemask at term to infants with BPD did not improve ventilation, gas-mixing efficiency in distal airways, or oxygenation despite an increase in FRC. We speculate that instead of promoting recruitment of unventilated lung volumes, increasing the end-expiratory pressure in infants with BPD may lead to an overexpansion of already ventilated parts of the lung, causing further compromise of lung function. Copyright © 2012 S. Karger AG, Basel.

Feasibility of quantitative regional ventilation and perfusion mapping with phase-resolved functional lung (PREFUL) MRI in healthy volunteers and COPD, CTEPH, and CF patients.

PubMed

Voskrebenzev, Andreas; Gutberlet, Marcel; Klimeš, Filip; Kaireit, Till F; Schönfeld, Christian; Rotärmel, Alexander; Wacker, Frank; Vogel-Claussen, Jens

2018-04-01

In this feasibility study, a phase-resolved functional lung imaging postprocessing method for extraction of dynamic perfusion (Q) and ventilation (V) parameters using a conventional 1H lung MRI Fourier decomposition acquisition is introduced. Time series of coronal gradient-echo MR images with a temporal resolution of 288 to 324 ms of two healthy volunteers, one patient with chronic thromboembolic hypertension, one patient with cystic fibrosis, and one patient with chronic obstructive pulmonary disease were acquired at 1.5 T. Using a sine model to estimate cardiac and respiratory phases of each image, all images were sorted to reconstruct full cardiac and respiratory cycles. Time to peak (TTP), V/Q maps, and fractional ventilation flow-volume loops were calculated. For the volunteers, homogenous ventilation and perfusion TTP maps (V-TTP, Q-TTP) were obtained. The chronic thromboembolic hypertension patient showed increased perfusion TTP in hypoperfused regions in visual agreement with dynamic contrast-enhanced MRI, which improved postpulmonary endaterectomy surgery. Cystic fibrosis and chronic obstructive pulmonary disease patients showed a pattern of increased V-TTP and Q-TTP in regions of hypoventilation and decreased perfusion. Fractional ventilation flow-volume loops of the chronic obstructive pulmonary disease patient were smaller in comparison with the healthy volunteer, and showed regional differences in visual agreement with functional small airways disease and emphysema on CT. This study shows the feasibility of phase-resolved functional lung imaging to gain quantitative information regarding regional lung perfusion and ventilation without the need for ultrafast imaging, which will be advantageous for future clinical translation. Magn Reson Med 79:2306-2314, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

World Trade Center dyspnea: bronchiolitis obliterans with functional improvement: a case report.

PubMed

Mann, Jack M; Sha, Kenneth K; Kline, Gary; Breuer, Frank-Uwe; Miller, Albert

2005-09-01

Bronchiolitis obliterans is a severe, often progressive, lung disease characterized by cough, exertional dyspnea, and airflow obstruction. It has been ascribed to specific causes such as lung or bone marrow transplant, medications for rheumatoid disease, and most recently in association with exposure to environmental agents. A 42-year-old, previously healthy New York City Highway Patrol officer who arrived at the World Trade Center (WTC), "ground zero," early on September 11, 2001 was evaluated. He has been followed for over 2 years with serial chest radiographs, CT scans, and pulmonary function studies. He eventually underwent an open lung biopsy. His dyspnea started on September 12, 2001 and progressed despite aggressive therapy with inhaled bronchodilator as well as oral and inhaled corticosteroids. At no time did he have any radiographic evidence of pulmonary disease. His forced vital capacity (FVC) decreased from 5.32 L in October 2001 to 2.86 L in January 2003. He underwent an open lung biopsy because of the persistent exertional dyspnea coupled with the loss of over 2 L of lung volume. The pathological findings were chronic bronchiolitis with focal obliterative bronchiolitis and rare non-necrotizing granuloma. Symptoms and pulmonary function improved after therapy with Azithromycin was added to his treatment. This process is believed to be secondary to his massive exposure to the cloud of dust that followed the collapse of the WTC. It is our conviction that many of those present at the WTC on September 11 who have persistent dyspnea and deterioration of pulmonary function may have a similar pathologic process despite absence of abnormalities on CT of the chest. In view of the many signs and symptoms seen in first responders we feel that these findings provide important information about the pathophysiology and treatment of progressive disease resulting from this exposure.

Biomarkers for radiation pneumonitis using non-invasive molecular imaging

PubMed Central

Medhora, Meetha; Haworth, Steven; Liu, Yu; Narayanan, Jayashree; Gao, Feng; Zhao, Ming; Audi, Said; Jacobs, Elizabeth R.; Fish, Brian L.; Clough, Anne V.

2016-01-01

Rationale Our goal is to develop minimally-invasive biomarkers for predicting radiation-induced lung injury before symptoms develop. Currently there are no biomarkers that can predict radiation pneumonitis. Radiation damage to the whole lung is a serious risk in nuclear accidents or in case of radiological terrorism. Our previous studies have shown a single dose of 15 Gy X-rays to the thorax causes severe pneumonitis in rats by 6–8 weeks. We have also developed a mitigator for radiation pneumonitis and fibrosis that can be started as late as 5 weeks after radiation. Methods We used two functional single photon emission computed tomography (SPECT) probes in vivo in irradiated rat lungs. Regional pulmonary perfusion was measured by injection of technetium labeled macroaggregated albumin (99mTc-MAA). Perfused volume was determined by comparing the volume of distribution of 99mTc-MAA to the anatomical lung volume obtained by micro-CT. A second probe, technetium labeled duramycin that binds to apoptotic cells, was used to measure pulmonary cell death in the same rat model. Results Perfused volume of lung was decreased by ~25% at 1, 2 and 3 weeks after 15 Gy and 99mTc-duramycin uptake was more than doubled at 2 and 3 weeks. There was no change in body weight, breathing rate or lung histology between irradiated and non-irradiated rats at these times. Pulmonary vascular resistance and vascular permeability measured in isolated perfused lungs ex vivo increased at 2 weeks after 15 Gy. Principal conclusions Our results suggest the potential for SPECT biomarkers for predicting radiation injury to the lungs before substantial functional or histological damage is observed. Early prediction of radiation pneumonitis will benefit those receiving radiation in the context of therapy, accidents or terrorism in time to initiate mitigation. PMID:27033892

Anti-sFlt-1 Therapy Preserves Lung Alveolar and Vascular Growth in Antenatal Models of Bronchopulmonary Dysplasia.

PubMed

Wallace, Bradley; Peisl, Amelie; Seedorf, Gregory; Nowlin, Taylor; Kim, Christina; Bosco, Jennifer; Kenniston, Jon; Keefe, Dennis; Abman, Steven H

2018-03-15

Pregnancies complicated by antenatal stress, including preeclampsia (PE) and chorioamnionitis (CA), increase the risk for bronchopulmonary dysplasia (BPD) in preterm infants, but biologic mechanisms linking prenatal factors with BPD are uncertain. Levels of sFlt-1 (soluble fms-like tyrosine kinase 1), an endogenous antagonist to VEGF (vascular endothelial growth factor), are increased in amniotic fluid and maternal blood in PE and associated with CA. Because impaired VEGF signaling has been implicated in the pathogenesis of BPD, we hypothesized that fetal exposure to sFlt-1 decreases lung growth and causes abnormal lung structure and pulmonary hypertension during infancy. To test this hypothesis, we studied the effects of anti-sFlt-1 monoclonal antibody (mAb) treatment on lung growth in two established antenatal models of BPD that mimic PE and CA induced by intraamniotic (i.a.) injections of sFlt-1 or endotoxin, respectively. In experimental PE, mAb was administered by three different approaches, including antenatal treatment by either i.a. instillation or maternal uterine artery infusion, or by postnatal intraperitoneal injections. With each strategy, mAb therapy improved infant lung structure as assessed by radial alveolar count, vessel density, right ventricular hypertrophy, and lung function. As found in the PE model, the adverse lung effects of i.a. endotoxin were also reduced by antenatal or postnatal mAb therapy. We conclude that treatment with anti-sFlt-1 mAb preserves lung structure and function and prevents right ventricular hypertrophy in two rat models of BPD of antenatal stress and speculate that early mAb therapy may provide a novel strategy for the prevention of BPD.

JNK signaling mediates EPHA2-dependent tumor cell proliferation, motility, and cancer stem cell-like properties in non-small cell lung cancer

PubMed Central

Song, Wenqiang; Ma, Yufang; Wang, Jialiang; Brantley-Sieders, Dana; Chen, Jin

2014-01-01

Recent genome-wide analyses in human lung cancer revealed that EPHA2 receptor tyrosine kinase is overexpressed in non-small cell lung cancer (NSCLC), and high levels of EPHA2 correlate with poor clinical outcome. However, the mechanistic basis for EPHA2-mediated tumor promotion in lung cancer remains poorly understood. Here we show that the JNK/c-JUN signaling mediates EPHA2-dependent tumor cell proliferation and motility. A screen of phospho-kinase arrays revealed a decrease in phospho-c-JUN levels in EPHA2 knockdown cells. Knockdown of EPHA2 inhibited p-JNK and p-c-JUN levels in approximately 50% of NSCLC lines tested. Treatment of parental cells with SP600125, a JNK inhibitor, recapitulated defects in EPHA2-deficient tumor cells; whereas constitutively activated JNK mutants were sufficient to rescue phenotypes. Knockdown of EPHA2 also inhibited tumor formation and progression in xenograft animal models in vivo. Furthermore, we investigated the role of EPHA2 in cancer stem-like cells. RNAi-mediated depletion of EPHA2 in multiple NSCLC lines decreased the ALDH positive cancer stem-like population and tumor spheroid formation in suspension. Depletion of EPHA2 in sorted ALDH positive populations markedly inhibited tumorigenicity in nude mice. Furthermore, analysis of a human lung cancer tissue microarray revealed a significant, positive association between EPHA2 and ALDH expression, indicating an important role for EPHA2 in human lung cancer stem-like cells. Collectively, these studies revealed a critical role of JNK signaling in EPHA2-dependent lung cancer cell proliferation and motility and a role for EPHA2 in cancer stem-like cell function, providing evidence for EPHA2 as a potential therapeutic target in NSCLC. PMID:24607842

Effects of pleural effusion drainage on oxygenation, respiratory mechanics, and hemodynamics in mechanically ventilated patients.

PubMed

Razazi, Keyvan; Thille, Arnaud W; Carteaux, Guillaume; Beji, Olfa; Brun-Buisson, Christian; Brochard, Laurent; Mekontso Dessap, Armand

2014-09-01

In mechanically ventilated patients, the effect of draining pleural effusion on oxygenation is controversial. We investigated the effect of large pleural effusion drainage on oxygenation, respiratory function (including lung volumes), and hemodynamics in mechanically ventilated patients after ultrasound-guided drainage. Arterial blood gases, respiratory mechanics (airway, pleural and transpulmonary pressures, end-expiratory lung volume, respiratory system compliance and resistance), and hemodynamics (blood pressure, heart rate, and cardiac output) were recorded before and at 3 and 24 hours (H24) after pleural drainage. The respiratory settings were kept identical during the study period. The mean volume of effusion drained was 1,579 ± 684 ml at H24. Uncomplicated pneumothorax occurred in two patients. Respiratory mechanics significantly improved after drainage, with a decrease in plateau pressure and a large increase in end-expiratory transpulmonary pressure. Respiratory system compliance, end-expiratory lung volume, and PaO2/FiO2 ratio all improved. Hemodynamics were not influenced by drainage. Improvement in the PaO2/FiO2 ratio from baseline to H24 was positively correlated with the increase in end-expiratory lung volume during the same time frame (r = 0.52, P = 0.033), but not with drained volume. A high value of pleural pressure or a highly negative transpulmonary pressure at baseline predicted limited lung expansion following effusion drainage. A lesser improvement in oxygenation occurred in patients with ARDS. Drainage of large (≥500 ml) pleural effusion in mechanically ventilated patients improves oxygenation and end-expiratory lung volume. Oxygenation improvement correlated with an increase in lung volume and a decrease in transpulmonary pressure, but was less so in patients with ARDS.

Ex Vivo Lung Perfusion: Establishment and Operationalization in Iran.

PubMed

Shafaghi, Shadi; Abbasi Dezfuli, Azizollah; Ansari Aval, Zahra; Sheikhy, Kambiz; Farzanegan, Behrooz; Mortaz, Esmaeil; Emami, Habib; Aigner, Clemens; Hosseini-Baharanchi, Fatemeh Sadat; Najafizadeh, Katayoun

2017-02-01

Although the number of lung transplants is limited because of general shortage of organ donors, ex vivo lung perfusion is a novel method with 2 main benefits, including better evaluation of lung potential and recovery of injured lungs. The main aim of this study was to establish and operationalize ex vivo lung perfusion as the first experience in Iran. This was a prospective operational research study on 5 cases, including 1 pig from Vienna Medical University and 4 patients from Masih Daneshvari Hospital. All organ donations from brain dead donors were evaluated according to lung transplant or ex vivo lung perfusion criteria from May 2013 to July 2015 in Tehran, Iran. If a donor did not have any sign of severe chest trauma or pneumonia but had poor oxygenation due to possible atelectasis or neurogenic pulmonary edema, their lungs were included for ex vivo lung perfusion. A successful trend in the difference between the pulmonary arterial Po2 and the left atrial Po2 was observed, as well as an increasing pattern in other functional parameters, including dynamic lung compliance and a decreasing trend in pulmonary vascular resistance. These initial trials indicate that ex vivo lung perfusion can lead to remarkable progress in lung transplant in Iran. They also provide several important pieces of guidance for successful ex vivo lung perfusion, including the necessity of following standard lung retrieval procedures and monitoring temperature and pressure precisely. The development of novel methods can provide opportunities for further research studies on lungs of deceased donors and lead to undiscovered findings. By keeping this science up to date in Iran and developing such new and creative methods, we can reveal effective strategies to promote the quality of donor lungs to support patients on transplant wait lists.

Low-grade systemic inflammation: a partial mediator of the relationship between diabetes and lung function.

PubMed

Giovannelli, Jonathan; Trouiller, Philippe; Hulo, Sébastien; Chérot-Kornobis, Natalie; Ciuchete, Alina; Edmé, Jean-Louis; Matran, Régis; Amouyel, Philippe; Meirhaeghe, Aline; Dauchet, Luc

2018-01-01

An association has been consistently found between diabetes mellitus and decreased lung function. We evaluated to what extent low-grade inflammation (as measured by the level of high-sensitivity C-reactive protein [hs-CRP]) could explain this relationship. A sample of 1878 middle-aged adults from the cross-sectional Enquête Littoral Souffle Air Biologie Environnement survey without self-reported pulmonary and atherosclerosis disease was included. A mediation analysis was performed to assess and quantify the hs-CRP level as a mediator of the relationship between diabetes and lung function. Diabetes was associated with higher hs-CRP level (+22.9%, 95% confidence interval = [5.1, 43.6]). The hs-CRP (>4 vs. ≤1 mg/L) was associated with lower percentage predicted values for the forced expiratory volume in the first second (FEV1) (-4% [-6.1, -1.9]) and forced vital capacity (FVC) (-4.4% [-6.5, -2.3]). Diabetes was associated with FEV1 (-3.5% [-5.8, -1.3]) and FVC (-3.6% [-5.9, -1.3]). The proportion of the effect that is mediated by hs-CRP was 12% [2.4, 37] and 13% [3.7, 39.4] for FEV1 and FVC, respectively. Our results suggest that low-grade systemic inflammation could only explain a small part of the relationship between diabetes and lung function. Copyright © 2017 Elsevier Inc. All rights reserved.

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

PubMed Central

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

2005-01-01

Objectives The aim of this study was to determine the effects of acute lung injury (ALI) on the gut epithelium and examine mechanisms underlying changes in crypt proliferation and apoptosis. The relationship between severity and timing of lung injury to intestinal pathology was also examined. Design Randomized, controlled study. Setting University research laboratory. Subjects Genetically inbred mice. Interventions Following induction of ALI, gut epithelial proliferation and apoptosis was assessed in a) C3H/HeN wild type and C3H/HeJ mice, that lack functional toll-like receptor 4 (TLR4, n=17), b) C57Bl/6 mice that received monoclonal anti-tumor necrosis factor-α (TNFα) or control antibody (n=22) and c) C57Bl/6 wild type and transgenic mice that overexpress Bcl-2 in their gut epithelium (n=21). Intestinal epithelial proliferation and death were also examined in animals with differing degrees of lung inflammation (n=24) as well as in a timecourse analysis following a fixed injury (n=18). Measurements and Main Results ALI caused decreased proliferation and increased apoptosis in crypt epithelial cells in all animals studied. C3H/HeJ mice had higher levels of proliferation than C3H/HeN animals without additional changes in apoptosis. Anti-TNFα antibody had no effect on gut epithelial proliferation or death. Overexpression of Bcl-2 did not change proliferation despite decreasing gut apoptosis. Proliferation and apoptosis were not correlated to severity of lung injury, as gut alterations were lost in mice with more severe ALI. Changes in both gut epithelial proliferation and death were apparent within 12 hours, but proliferation was decreased 36 hours following ALI while apoptosis returned to normal. Conclusions ALI causes disparate effects on crypt proliferation and apoptosis, which occur, at least in part, through differing mechanisms involving TLR4 and Bcl-2. Severity of lung injury does not correlate with perturbations in proliferation or death in the gut epithelium, and ALI-induced changes in intestinal epithelial proliferation persist longer than those in apoptosis. PMID:16215392

How do patients conceptualize chronic obstructive pulmonary disease?

PubMed

Goldman, R E; Mennillo, L; Stebbins, P; Parker, D R

2017-08-01

Chronic obstructive pulmonary disease (COPD) is a leading cause of death in the United States, yet even at risk or diagnosed patients misunderstand COPD and its consequences for their quality of life and mortality. This study explored how patients conceptualize the causes, symptoms, consequences, treatment, and risk for developing COPD. The study consisted of six focus groups: 39 participants who were adults > 40 and current smoker or have COPD symptoms, family history, or exposures. Although many participants had some familiarity with the breathing, lung function, physical, emotional, and social consequences of COPD, confusion and misunderstanding prevailed. Few knew that COPD, chronic bronchitis, and emphysema are synonymous. Some participants claimed that they "only" had bronchitis and/or emphysema and not COPD. Some participants described behavioral adaptations to decrease symptom impact and others expressed strong interest in learning how to increase daily functioning. Insufficient knowledge and persisting misconceptions about COPD can prevent patients from accessing life-enhancing strategies. Patients can benefit from (1) providers clarifying COPD's connection to chronic bronchitis and emphysema to aid them in recognizing the need for mitigating action; (2) encouraging smoking cessation, specifically to stem worsening of disease; and (3) explaining lifestyle adaptations for easing daily life despite decreased lung function.

Chronic exposure to emissions from photocopiers in copy shops causes oxidative stress and systematic inflammation among photocopier operators in India.

PubMed

Elango, Nithya; Kasi, Vallikkannu; Vembhu, Bhuvaneswari; Poornima, Jeyanthi Govindasamy

2013-09-11

We assessed indoor air quality in photocopier centers and investigated whether occupational exposure to emissions from photocopiers is associated with decline in lung function or changes in haematological parameters, oxidative stress and inflammatory status. Indoor air quality was monitored in five photocopier centers. Pulmonary function was assessed by spirometry in 81 photocopier operators (64 male and 17 female) and 43 healthy control (31 male and 12 female) subjects. Hematological status, serum thio-barbituric acid reactive substances (TBARS), total ferric reducing antioxidant capacity (FRAC), leukotriene B4 (LTB4), 8-isoprostane, C reactive protein (CRP), interleukin 8 (IL-8), clara cell protein (CC-16), intercellular adhesion molecule 1 (ICAM-1) and eosinophilic cationic protein (ECP) were analyzed. Relationships between cumulative exposure, lung function and inflammatory markers were assessed. PM10 and PM2.5 were above the permissible levels in all the photocopier centers, whereas the levels of carbon monoxide, nitrogen oxides, ozone, sulphur dioxide, lead, arsenic, nickel, ammonia, benzene and benzo(a)pyrene were within Indian ambient air quality standards. Lung function was similar in the photocopier operators and control subjects. Serum TBARS was significantly higher and FRAC was lower among photocopier operators when compared to healthy controls. Plasma IL-8, LTB4, ICAM-1 and ECP were significantly higher in the photocopier exposed group. Photocopiers emit high levels of particulate matter. Long term exposure to emissions from photocopiers was not associated with decreased lung function, but resulted in high oxidative stress and systemic inflammation leading to high risk of cardiovascular diseases.

Chronic exposure to emissions from photocopiers in copy shops causes oxidative stress and systematic inflammation among photocopier operators in India

PubMed Central

2013-01-01

Background We assessed indoor air quality in photocopier centers and investigated whether occupational exposure to emissions from photocopiers is associated with decline in lung function or changes in haematological parameters, oxidative stress and inflammatory status. Methods Indoor air quality was monitored in five photocopier centers. Pulmonary function was assessed by spirometry in 81 photocopier operators (64 male and 17 female) and 43 healthy control (31 male and 12 female) subjects. Hematological status, serum thio-barbituric acid reactive substances (TBARS), total ferric reducing antioxidant capacity (FRAC), leukotriene B4 (LTB4), 8-isoprostane, C reactive protein (CRP), interleukin 8 (IL-8), clara cell protein (CC-16), intercellular adhesion molecule 1 (ICAM-1) and eosinophilic cationic protein (ECP) were analyzed. Relationships between cumulative exposure, lung function and inflammatory markers were assessed. Results PM10 and PM2.5 were above the permissible levels in all the photocopier centers, whereas the levels of carbon monoxide, nitrogen oxides, ozone, sulphur dioxide, lead, arsenic, nickel, ammonia, benzene and benzo(a)pyrene were within Indian ambient air quality standards. Lung function was similar in the photocopier operators and control subjects. Serum TBARS was significantly higher and FRAC was lower among photocopier operators when compared to healthy controls. Plasma IL-8, LTB4, ICAM-1 and ECP were significantly higher in the photocopier exposed group. Conclusions Photocopiers emit high levels of particulate matter. Long term exposure to emissions from photocopiers was not associated with decreased lung function, but resulted in high oxidative stress and systemic inflammation leading to high risk of cardiovascular diseases. PMID:24025094

Maternal Dietary Docosahexaenoic Acid Supplementation Attenuates Fetal Growth Restriction and Enhances Pulmonary Function in a Newborn Mouse Model of Perinatal Inflammation123

PubMed Central

Velten, Markus; Britt, Rodney D.; Heyob, Kathryn M.; Tipple, Trent E.; Rogers, Lynette K.

2014-01-01

The preterm infant is often exposed to maternal and neonatal inflammatory stimuli and is born with immature lungs, resulting in a need for oxygen therapy. Nutritional intervention with docosahexaenoic acid (DHA; 6.3 g/kg of diet) has been shown to attenuate inflammation in various human diseases. Previous studies demonstrated that maternal DHA supplementation during late gestation and lactation attenuated hyperoxic lung injury in newborn mouse pups. In the present studies, we tested the hypothesis that DHA supplementation to the dam would reduce hyperoxic lung injury and growth deficits in a more severe model of systemic maternal inflammation, including lipopolysaccharide (LPS) and neonatal hyperoxia exposure. On embryonic day 16, dams were placed on DHA (6.3 g DHA/kg diet) or control diets and injected with saline or LPS. Diets were maintained through weaning. At birth, pups were placed in room air or hyperoxia for 14 d. Improvements in birth weight (P < 0.01), alveolarization (P ≤ 0.01), and pulmonary function (P ≤ 0.03) at 2 and 8 wk of age were observed in pups exposed to perinatal inflammation and born to DHA-supplemented dams compared with control diet–exposed pups. These improvements were associated with decreases in tissue macrophage numbers (P < 0.01), monocyte chemoattractant protein-1 expression (P ≤ 0.05), and decreases in soluble receptor for advanced glycation end products concentrations (P < 0.01) at 2 and 8 wk. Furthermore, DHA supplementation attenuated pulmonary fibrosis, which was associated with the reduction of matrix metalloproteinases 2, 3, and 8 (P ≤ 0.03) and collagen mRNA (P ≤ 0.05), and decreased collagen (P < 0.01) and vimentin (P ≤ 0.03) protein concentrations. In a model of severe inflammation, maternal DHA supplementation lessened inflammation and improved lung growth in the offspring. Maternal supplementation with DHA may be a therapeutic strategy to reduce neonatal inflammation. PMID:24453131

HIV Impairs Lung Epithelial Integrity and Enters the Epithelium to Promote Chronic Lung Inflammation.

PubMed

Brune, Kieran A; Ferreira, Fernanda; Mandke, Pooja; Chau, Eric; Aggarwal, Neil R; D'Alessio, Franco R; Lambert, Allison A; Kirk, Gregory; Blankson, Joel; Drummond, M Bradley; Tsibris, Athe M; Sidhaye, Venkataramana K

2016-01-01

Several clinical studies show that individuals with HIV are at an increased risk for worsened lung function and for the development of COPD, although the mechanism underlying this increased susceptibility is poorly understood. The airway epithelium, situated at the interface between the external environment and the lung parenchyma, acts as a physical and immunological barrier that secretes mucins and cytokines in response to noxious stimuli which can contribute to the pathobiology of chronic obstructive pulmonary disease (COPD). We sought to determine the effects of HIV on the lung epithelium. We grew primary normal human bronchial epithelial (NHBE) cells and primary lung epithelial cells isolated from bronchial brushings of patients to confluence and allowed them to differentiate at an air- liquid interface (ALI) to assess the effects of HIV on the lung epithelium. We assessed changes in monolayer permeability as well as the expression of E-cadherin and inflammatory modulators to determine the effect of HIV on the lung epithelium. We measured E-cadherin protein abundance in patients with HIV compared to normal controls. Cell associated HIV RNA and DNA were quantified and the p24 viral antigen was measured in culture supernatant. Surprisingly, X4, not R5, tropic virus decreased expression of E-cadherin and increased monolayer permeability. While there was some transcriptional regulation of E-cadherin, there was significant increase in lysosome-mediated protein degradation in cells exposed to X4 tropic HIV. Interaction with CXCR4 and viral fusion with the epithelial cell were required to induce the epithelial changes. X4 tropic virus was able to enter the airway epithelial cells but not replicate in these cells, while R5 tropic viruses did not enter the epithelial cells. Significantly, X4 tropic HIV induced the expression of intercellular adhesion molecule-1 (ICAM-1) and activated extracellular signal-regulated kinase (ERK). We demonstrate that HIV can enter airway epithelial cells and alter their function by impairing cell-cell adhesion and increasing the expression of inflammatory mediators. These observed changes may contribute local inflammation, which can lead to lung function decline and increased susceptibility to COPD in HIV patients.

Sirolimus alters lung pathology and viral load following influenza A virus infection.

PubMed

Alsuwaidi, Ahmed R; George, Junu A; Almarzooqi, Saeeda; Hartwig, Stacey M; Varga, Steven M; Souid, Abdul-Kader

2017-07-11

Inhibitors of mTOR, such as sirolimus, have been shown to induce thymus involution and inflammatory lung disease in mice. The latter effect supports the role of this serine/threonine kinase in ameliorating lung inflammation. Other studies have shown sirolimus reduces/delays lung disease associated with various strains of influenza A virus (IAV). Thus, the effects of mTOR inhibitors on influenza infection deserve further studies. Here, we examined the changes in lung viral copies, pathology and pulmonary function associated with IAV (A/PR/8/34) infection in mice treated with sirolimus. Body weight loss peaked between days 6-11 post-infection and was more severe in IAV-infected mice that were administered sirolimus as compared to mice that received IAV alone (p = 0.030). Natural log viral gene copies, mean ± SD per mg lung tissue, in IAV-infected mice that were administered sirolimus were 17.31 ± 1.27 on day 4, 19.31 ± 7.46 on day 10, and 0 on day 25. The corresponding number of copies in mice that received IAV alone were 18.56 ± 0.95 on day 4 (p = 0.132), 1.52 ± 1.39 on day 10 (p = 0.008), and 0 on day 25. Lung pathology was evident on days 4, 10, and 25 post infection, with mean ± SD inflammatory score of 9.0 ± 4.5 in IAV-infected mice that were administered sirolimus, as compared to 11.5 ± 4.5 (p = 0.335) in mice received IAV alone (maximum score, 26.0). Impaired lung function was evident in IAV-infected mice on days 4 and 10, as demonstrated by increased airway resistance and decreased compliance. In this model, the effects of sirolimus on influenza infection included severe weight loss and modified viral replication, respiratory function and lung inflammation. The adverse events associated with sirolimus treatment are consistent with its potent immunosuppressive activity and, thus, preclude its use in IAV infection.

Phosphorylation of Extracellular Signal-Regulated Kinase (ERK)-1/2 Is Associated with the Downregulation of Peroxisome Proliferator–Activated Receptor (PPAR)-γ during Polymicrobial Sepsis

PubMed Central

Kaplan, Jennifer M; Hake, Paul W; Denenberg, Alvin; Nowell, Marchele; Piraino, Giovanna; Zingarelli, Basilia

2010-01-01

Peroxisome proliferator–activated receptor (PPAR)-γ is a ligand-activated transcription factor and regulates inflammation. Posttranslational modifications regulate the function of PPARγ, potentially affecting inflammation. PPARγ contains a mitogen-activated protein kinase (MAPK) site, and phosphorylation by extracellular signal-regulated kinase (ERK)-1/2 leads to inhibition of PPARγ. This study investigated the kinetics of PPARγ expression and activation in parenchymal and immune cells in sepsis using the MAPK/ERK kinase (MEK)-1 inhibitor, an upstream kinase of ERK1/2. Adult male Sprague Dawley rats were subjected to polymicrobial sepsis by cecal ligation and puncture. Rats received intraperitoneal injection of vehicle or the MEK1 inhibitor PD98059 (5 mg/kg) 30 min before cecal ligation and puncture. Rats were euthanized at 0, 1, 3, 6 and 18 h after cecal ligation and puncture. Control animals used were animals at time 0 h. Lung, plasma and peripheral blood mononuclear cells (PBMCs) were collected for biochemical assays. In vehicle-treated rats, polymicrobial sepsis resulted in significant lung injury. In the lung and PBMCs, nuclear levels of PPARγ were decreased and associated with an increase in phosphorylated PPARγ and phosphorylated ERK1/2 levels. Treatment with the MEK1 inhibitor increased the antiinflammatory plasma adipokine adiponectin, restored PPARγ expression in PBMCs and lung, and decreased lung injury. The inflammatory effects of sepsis cause changes in PPARγ expression and activation, in part, because of phosphorylation of PPARγ by ERK1/2. This phosphorylation can be reversed by ERK1/2 inhibition, thereby improving lung injury. PMID:20809049

Preoperative use of incentive spirometry does not affect postoperative lung function in bariatric surgery.

PubMed

Cattano, Davide; Altamirano, Alfonso; Vannucci, Andrea; Melnikov, Vladimir; Cone, Chelsea; Hagberg, Carin A

2010-11-01

Morbidly obese patients undergoing general anesthesia for laparoscopic bariatric surgery are considered at increased risk of a postoperative decrease in lung function. The purpose of this study was to determine whether a systematic use of incentive spirometry (IS) prior to surgery could help patients to preserve their respiratory function better in the postoperative period. Forty-one morbidly obese (body mass index [BMI] > 40 kg/m²) candidates for laparoscopic bariatric surgery were consented in the study. All patients were taught how to use an incentive spirometer but then were randomized blindly into 2 groups. The control group was instructed to use the incentive spirometer for 3 breaths, once per day. The treatment group was requested to use the incentive spirometer for 10 breaths, 5 times per day. Twenty experimental (mean BMI of 48.9 ± 5.67 kg/m²) and 21 control patients (mean BMI of 48.3 ± 6.96 kg/m²) were studied. The initial mean inspiratory capacity (IC) was 2155 ± 650.08 (SD) cc and 2171 ± 762.98 cc in the experimental and control groups, respectively. On the day of surgery, the mean IC was 2275 ± 777.56 cc versus 2254.76 ± 808.84 cc, respectively. On postoperative day 1, both groups experienced a significant drop of their IC, with volumes of 1458 ± 613.87 cc (t test P < 0.001) and 1557.89 ± 814.67 cc (t test P < 0.010), respectively. Our results suggest that preoperative use of the IS does not lead to significant improvements of inspiratory capacity and that it is a not a useful resource to prevent postoperative decrease in lung function. Copyright © 2010 Mosby, Inc. All rights reserved.

Lung Volume Reduction in Pulmonary Emphysema from the Radiologist's Perspective.

PubMed

Doellinger, F; Huebner, R H; Kuhnigk, J M; Poellinger, A

2015-08-01

Pulmonary emphysema causes decrease in lung function due to irreversible dilatation of intrapulmonary air spaces, which is linked to high morbidity and mortality. Lung volume reduction (LVR) is an invasive therapeutical option for pulmonary emphysema in order to improve ventilation mechanics. LVR can be carried out by lung resection surgery or different minimally invasive endoscopical procedures. All LVR-options require mandatory preinterventional evaluation to detect hyperinflated dysfunctional lung areas as target structures for treatment. Quantitative computed tomography can determine the volume percentage of emphysematous lung and its topographical distribution based on the lung's radiodensity. Modern techniques allow for lobebased quantification that facilitates treatment planning. Clinical tests still play the most important role in post-interventional therapy monitoring, but CT is crucial in the detection of postoperative complications and foreshadows the method's high potential in sophisticated experimental studies. Within the last ten years, LVR with endobronchial valves has become an extensively researched minimally-invasive treatment option. However, this therapy is considerably complicated by the frequent occurrence of functional interlobar shunts. The presence of "collateral ventilation" has to be ruled out prior to valve implantations, as the presence of these extraanatomical connections between different lobes may jeopardize the success of therapy. Recent experimental studies evaluated the automatic detection of incomplete lobar fissures from CT scans, because they are considered to be a predictor for the existence of shunts. To date, these methods are yet to show acceptable results. Today, surgical and various minimal invasive methods of lung volume reduction are in use. Radiological and nuclear medical examinations are helpful in the evaluation of an appropriate lung area. Imaging can detect periinterventional complications. Reduction of lung volume has not yet been conclusively proven to be effective and is a therapeutical option with little scientific evidence. © Georg Thieme Verlag KG Stuttgart · New York.

Experimental determination of the respiratory tract deposition of diesel combustion particles in patients with chronic obstructive pulmonary disease

PubMed Central

2012-01-01

Background Air pollution, mainly from combustion, is one of the leading global health risk factors. A susceptible group is the more than 200 million people worldwide suffering from chronic obstructive pulmonary disease (COPD). There are few data on lung deposition of airborne particles in patients with COPD and none for combustion particles. Objectives To determine respiratory tract deposition of diesel combustion particles in patients with COPD during spontaneous breathing. Methods Ten COPD patients and seven healthy subjects inhaled diesel exhaust particles generated during idling and transient driving in an exposure chamber. The respiratory tract deposition of the particles was measured in the size range 10–500 nm during spontaneous breathing. Results The deposited dose rate increased with increasing severity of the disease. However, the deposition probability of the ultrafine combustion particles (< 100 nm) was decreased in COPD patients. The deposition probability was associated with both breathing parameters and lung function, but could be predicted only based on lung function. Conclusions The higher deposited dose rate of inhaled air pollution particles in COPD patients may be one of the factors contributing to their increased vulnerability. The strong correlations between lung function and particle deposition, especially in the size range of 20–30 nm, suggest that altered particle deposition could be used as an indicator respiratory disease. PMID:22839109

Prognostic value of serum zinc levels in patients with acute HC/zinc chloride smoke inhalation

PubMed Central

Xie, Fei; Zhang, Xingang; Xie, Lixin

2017-01-01

Abstract Hexachloroethane (HC)/zinc chloride (ZnCl, smoke bomb) exposure in the military setting results in lung injury which is uncommon and has been rarely described in previous studies. The aim of this study is to investigate the correlation between the serum zinc in patients with HC/ZnCl smoke inhalation lung injury and disease severity. A total of 15 patients with HC/ZnCl-related conditions were recruited in this study. The serum zinc level and the pulmonary function tests and liver function tests including total lung capacity (TLC), forced vital capacity (FVC), forced expiratory pressure in 1 second (FEV1), alanine aminotransferase (ALT), and aspartate transaminase (AST) were analyzed. Eleven cases had mild clinical manifestations. Four cases rapidly developed features typical of severe adult respiratory distress syndrome. The level of serum zinc was increased, but FVC, FEV1, and TLC was decreased significantly in the moderate and severe cases. In addition, the serum zinc level correlated well with the TLC, FVC, and FEV1 (r = −0.587, −0.626, −0.617, respectively; P = .027, .017, .019, respectively). The 4 cases in moderate and severe group had delayed impairment of liver functions after the accident. This study suggested that the serum zinc level may be associated with the severity of lung and liver injuries after HC/ZnCl smoke inhalation. PMID:28953660

Shrinking lung syndrome as a manifestation of pleuritis: a new model based on pulmonary physiological studies.

PubMed

Henderson, Lauren A; Loring, Stephen H; Gill, Ritu R; Liao, Katherine P; Ishizawar, Rumey; Kim, Susan; Perlmutter-Goldenson, Robin; Rothman, Deborah; Son, Mary Beth F; Stoll, Matthew L; Zemel, Lawrence S; Sandborg, Christy; Dellaripa, Paul F; Nigrovic, Peter A

2013-03-01

The pathophysiology of shrinking lung syndrome (SLS) is poorly understood. We sought to define the structural basis for this condition through the study of pulmonary mechanics in affected patients. Since 2007, most patients evaluated for SLS at our institutions have undergone standardized respiratory testing including esophageal manometry. We analyzed these studies to define the physiological abnormalities driving respiratory restriction. Chest computed tomography data were post-processed to quantify lung volume and parenchymal density. Six cases met criteria for SLS. All presented with dyspnea as well as pleurisy and/or transient pleural effusions. Chest imaging results were free of parenchymal disease and corrected diffusing capacities were normal. Total lung capacities were 39%-50% of predicted. Maximal inspiratory pressures were impaired at high lung volumes, but not low lung volumes, in 5 patients. Lung compliance was strikingly reduced in all patients, accompanied by increased parenchymal density. Patients with SLS exhibited symptomatic and/or radiographic pleuritis associated with 2 characteristic physiological abnormalities: (1) impaired respiratory force at high but not low lung volumes; and (2) markedly decreased pulmonary compliance in the absence of identifiable interstitial lung disease. These findings suggest a model in which pleural inflammation chronically impairs deep inspiration, for example through neural reflexes, leading to parenchymal reorganization that impairs lung compliance, a known complication of persistently low lung volumes. Together these processes could account for the association of SLS with pleuritis as well as the gradual symptomatic and functional progression that is a hallmark of this syndrome.

Why does the lung hyperinflate?

PubMed

Ferguson, Gary T

2006-04-01

Patients with chronic obstructive pulmonary disease (COPD) often have some degree of hyperinflation of the lungs. Hyperinflated lungs can produce significant detrimental effects on breathing, as highlighted by improvements in patient symptoms after lung volume reduction surgery. Measures of lung volumes correlate better with impairment of patient functional capabilities than do measures of airflow. Understanding the mechanisms by which hyperinflation occurs in COPD provides better insight into how treatments can improve patients' health. Both static and dynamic processes can contribute to lung hyperinflation in COPD. Static hyperinflation is caused by a decrease in elasticity of the lung due to emphysema. The lungs exert less recoil pressure to counter the recoil pressure of the chest wall, resulting in an equilibrium of recoil forces at a higher resting volume than normal. Dynamic hyperinflation is more common and can occur independent of or in addition to static hyperinflation. It results from air being trapped within the lungs after each breath due to a disequilibrium between the volumes inhaled and exhaled. The ability to fully exhale depends on the degree of airflow limitation and the time available for exhalation. These can both vary, causing greater hyperinflation during exacerbations or increased respiratory demand, such as during exercise. Reversibility of dynamic hyperinflation offers the possibility for intervention. Use of bronchodilators with prolonged durations of action, such as tiotropium, can sustain significant reductions in lung inflation similar in effect to lung volume reduction surgery. How efficacy of bronchodilators is assessed may, therefore, need to be reevaluated.

Impact of pulmonary rehabilitation on postoperative complications in patients with lung cancer and chronic obstructive pulmonary disease.

PubMed

Saito, Hajime; Hatakeyama, Kazutoshi; Konno, Hayato; Matsunaga, Toshiki; Shimada, Yoichi; Minamiya, Yoshihiro

2017-09-01

Given the extent of the surgical indications for pulmonary lobectomy in breathless patients, preoperative care and evaluation of pulmonary function are increasingly necessary. The aim of this study was to assess the contribution of preoperative pulmonary rehabilitation (PR) for reducing the incidence of postoperative pulmonary complications in non-small cell lung cancer (NSCLC) patients with chronic obstructive pulmonary disease (COPD). The records of 116 patients with COPD, including 51 patients who received PR, were retrospectively analyzed. Pulmonary function testing, including slow vital capacity (VC) and forced expiratory volume in one second (FEV 1 ), was obtained preoperatively, after PR, and at one and six months postoperatively. The recovery rate of postoperative pulmonary function was standardized for functional loss associated with the different resected lung volumes. Propensity score analysis generated matched pairs of 31 patients divided into PR and non-PR groups. The PR period was 18.7 ± 12.7 days in COPD patients. Preoperative pulmonary function was significantly improved after PR (VC 5.3%, FEV 1 5.5%; P < 0.05). The FEV 1 recovery rate one month after surgery was significantly better in the PR (101.6%; P < 0.001) than in the non-PR group (93.9%). In logistic regression analysis, predicted postoperative FEV 1 , predicted postoperative %FEV 1 , and PR were independent factors related to postoperative pulmonary complications after pulmonary lobectomy (odds ratio 18.9, 16.1, and 13.9, respectively; P < 0.05). PR improved the recovery rate of pulmonary function after lobectomy in the early period, and may decrease postoperative pulmonary complications. © 2017 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

[Abnormal expression of genes that regulate retinoid metabolism and signaling in non-small-cell lung cancer].

PubMed

Kuznetsova, E S; Zinovieva, O L; Oparina, N Yu; Prokofjeva, M M; Spirin, P V; Favorskaya, I A; Zborovskaya, I B; Lisitsyn, N A; Prassolov, V S; Mashkova, T D

2016-01-01

Retinoids are signaling molecules that control a wide variety of cellular processes and possess antitumor activity. This work presents a comprehensive description of changes in the expression of 23 genes that regulate retinoid metabolism and signaling in non-small-cell lung cancer tumors compared to adjacent normal tissues obtained using RT-PCR. Even at early stages of malignant transformation, a significant decrease in ADH1B, ADH3, RDHL, and RALDH1 mRNA levels was observed in 82, 79, 73, and 64% of tumor specimens, respectively, and a considerable increase in AKR1B10 mRNA content was observed in 80% of tumors. Dramatic changes in the levels of these mRNAs can impair the synthesis of all-trans retinoic acid, a key natural regulatory retinoid. Apart from that, it was found that mRNA levels of nuclear retinoid receptor genes RXRγ, RARα, RXRα, and gene RDH11 were significantly decreased in 80, 67, 57, and 66% of tumor specimens, respectively. Thus, neoplastic transformation of lung tissue cells is accompanied with deregulated expression of key genes of retinoid metabolism and function.

Ventilatory responses to exercise training in obese adolescents.

PubMed

Mendelson, Monique; Michallet, Anne-Sophie; Estève, François; Perrin, Claudine; Levy, Patrick; Wuyam, Bernard; Flore, Patrice

2012-10-15

The aim of this study was to examine ventilatory responses to training in obese adolescents. We assessed body composition, pulmonary function and ventilatory responses (among which expiratory flow limitation and operational lung volumes) during progressive cycling exercise in 16 obese adolescents (OB) before and after 12 weeks of exercise training and in 16 normal-weight volunteers. As expected, obese adolescents' resting expiratory reserve volume was lower and inversely correlated with thoraco-abdominal fat mass (r = -0.74, p<0.0001). OB presented lower end expiratory (EELV) and end inspiratory lung volumes (EILV) at rest and during submaximal exercise, and modest expiratory flow limitation. After training, OB increased maximal aerobic performance (+19%) and maximal inspiratory pressure (93.7±31.4 vs. 81.9±28.2 cm H2O, +14%) despite lack of decrease in trunk fat and body weight. Furthermore, EELV and EILV were greater during submaximal exercise (+11% and +9% in EELV and EILV, respectively), expiratory flow limitation delayed but was not accompanied by increased V(T). However, submaximal exertional symptoms (dyspnea and leg discomfort) were significantly decreased (-71.3% and -70.7%, respectively). Our results suggest that exercise training can improve pulmonary function at rest (static inspiratory muscle strength) and exercise (greater operating lung volumes and delayed expiratory flow limitation) but these modifications did not entirely account for improved dyspnea and exercise performance in obese adolescents. Copyright © 2012 Elsevier B.V. All rights reserved.

Correlation between thoracolumbar curvatures and respiratory function in older adults.

PubMed

Rahman, Nor Najwatul Akmal Ab; Singh, Devinder Kaur Ajit; Lee, Raymond

2017-01-01

Aging is associated with alterations in thoracolumbar curvatures and respiratory function. Research information regarding the correlation between thoracolumbar curvatures and a comprehensive examination of respiratory function parameters in older adults is limited. The aim of the present study was to examine the correlation between thoracolumbar curvatures and respiratory function in community-dwelling older adults. Thoracolumbar curvatures (thoracic and lumbar) were measured using a motion tracker. Respiratory function parameters such as lung function, respiratory rate, respiratory muscle strength and respiratory muscle thickness (diaphragm and intercostal) were measured using a spirometer, triaxial accelerometer, respiratory pressure meter and ultrasound imaging, respectively. Sixty-eight community-dwelling older males and females from Kuala Lumpur, Malaysia, with mean (standard deviation) age of 66.63 (5.16) years participated in this cross-sectional study. The results showed that mean (standard deviation) thoracic curvature angle and lumbar curvature angles were -46.30° (14.66°) and 14.10° (10.58°), respectively. There was a significant negative correlation between thoracic curvature angle and lung function (forced expiratory volume in 1 second: r =-0.23, P <0.05; forced vital capacity: r =-0.32, P <0.05), quiet expiration intercostal thickness ( r =-0.22, P <0.05) and deep expiration diaphragm muscle thickness ( r =-0.21, P <0.05). The lumbar curvature angle had a significant negative correlation with respiratory muscle strength ( r =-0.29, P <0.05) and diaphragm muscle thickness at deep inspiration ( r =-0.22, P <0.05). However, respiratory rate was correlated neither with thoracic nor with lumbar curvatures. The findings of this study suggest that increase in both thoracic and lumbar curvatures is correlated with decrease in respiratory muscle strength, respiratory muscle thickness and some parameters of lung function. Clinically, both thoracic and lumbar curvatures, respiratory muscles and lung function should be taken into consideration in the holistic management of respiratory function among older adults.

Scenarios of future lung cancer incidence by educational level: Modelling study in Denmark.

PubMed

Menvielle, Gwenn; Soerjomataram, Isabelle; de Vries, Esther; Engholm, Gerda; Barendregt, Jan J; Coebergh, Jan Willem; Kunst, Anton E

2010-09-01

To model future trends in lung cancer incidence in Denmark by education under different scenarios for cigarette smoking. Lung cancer incidence until 2050 was modelled using Prevent software. We estimated lung cancer incidence under a baseline scenario and under four alternative scenarios for smoking reduction: decreasing initiation rates among the young, increasing cessation rates among smokers, a scenario combining both changes and a levelling-up scenario in which people with low and medium levels of education acquired the smoking prevalence of the highly educated. Danish National Health Interview Surveys (1987-2005) and cancer registry data combined with individual education status from Statistics Denmark were used for empirical input. Under the baseline scenario, lung cancer rates are expected to decrease for most educational groups during the next few decades, but educational inequalities will increase further. Under the alternative scenarios, an additional decrease in lung cancer rates will be observed from 2030 onwards, but only from 2050 onwards it will be observed under the initiation scenario. The cessation and the combined scenarios show the largest decrease in lung cancer rates for all educational groups. However, in none of these scenarios would the relative differences between educational groups be reduced. A modest decrease in these inequalities will be observed under the levelling-up scenario. Our analyses show that relative inequalities in lung cancer incidence rates will tend to increase. They may be reduced to a small extent if the smoking prevalence of people with a low level of education was to converge towards those more highly educated people. An important decrease in lung cancer rates will be observed in all educational groups, however, especially when focusing on both initiation and cessation strategies. Copyright © 2010 Elsevier Ltd. All rights reserved.

Impact of spinal anaesthesia on peri-operative lung volumes in obese and morbidly obese female patients.

PubMed

Regli, A; von Ungern-Sternberg, B S; Reber, A; Schneider, M C

2006-03-01

Although obesity predisposes to postoperative pulmonary complications, data on the relationship between body mass index (BMI) and peri-operative respiratory performance are limited. We prospectively studied the impact of spinal anaesthesia, obesity and vaginal surgery on lung volumes measured by spirometry in 28 patients with BMI 30-40 kg.m(-2) and in 13 patients with BMI > or = 40 kg.m(-2). Vital capacity, forced vital capacity, forced expiratory volume in 1 s, mid-expiratory and peak expiratory flows were measured during the pre-operative visit (baseline), after effective spinal anaesthesia with premedication, and after the operation at 20 min, 1 h, 2 h, and 3 h (after mobilisation). Spinal anaesthesia and premedication were associated with a significant decrease in spirometric parameters. Spinal anaesthesia and premedication were associated with a significant decrease in spirometric parameters; mean (SD) vital capacities were - 19% (6.4) in patients with BMI 30-40 kg.m(-2) and - 33% (9.0) in patients with BMI > 40 kg.m(-2). The decrease of lung volumes remained constant for 2 h, whereas 3 h after the operation and after mobilisation, spirometric parameters significantly improved in all patients. This study showed that both spinal anaesthesia and obesity significantly impaired peri-operative respiratory function.

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

SU-E-J-87: Ventilation Weighting Effect On Mean Doses of Both Side Lungs for Patients with Advanced Stage Lung Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qu, H; Xia, P; Yu, N

Purpose: To study ventilation weighting effect on radiation doses to both side lungs for patients with advanced stage lung cancer. Methods: Fourteen patients with advanced stage lung cancer were included in this retrospective study. Proprietary software was developed to calculate the lung ventilation map based on 4DCT images acquired for radiation therapy. Two phases of inhale (0%) and exhale (50%) were used for the lung ventilation calculations. For each patient, the CT images were resampled to the same dose calculation resolution of 3mmx3mmx3mm. The ventilation distribution was then normalized by the mean value of the ventilation. The ventilation weighted dosemore » was calculated by applying linearly weighted ventilation to the dose of each pixel. The lung contours were automatically delineated from patient CT image with lung window, excluding the tumor and high density tissues. For contralateral and ipsilateral lungs, the mean lung doses from the original plan and ventilation weighted mean lung doses were compared using two tail t-Test. Results: The average of mean dose was 6.1 ±3.8Gy for the contralateral lungs, and 26.2 ± 14.0Gy for the ipsilateral lungs. The average of ventilation weighted dose was 6.3± 3.8Gy for the contralateral lungs and 24.6 ± 13.1Gy for the ipsilateral lungs. The statistics analysis shows the significance of the mean dose increase (p<0.015) for the contralateral lungs and decrease (p<0.005) for the ipsilateral lungs. Conclusion: Ventilation weighted doses were greater than the un-weighted doses for contralateral lungs and smaller for ipsilateral lungs. This Result may be helpful to understand the radiation dosimetric effect on the lung function and provide planning guidance for patients with advance stage lung cancer.« less

[Prevention and control of air pollution needs to strengthen further study on health damage caused by air pollution].

PubMed

Wu, T C

2016-08-06

Heath issues caused by air pollution such as particulate matter (PM) are much concerned and focused among air, water and soil pollutions because human breathe air for whole life span. Present comments will review physical and chemical characteristics of PM2.5 and PM10; Dose-response associations of PM10, PM2.5 and their components with mortality and risk of cardiopulmonary diseases, early health damages such as the decrease of lung functions and heart rate variability, DNA damage; And the roles of genetic variations and epigenetic changes in lung functions and heart rate variability, DNA damage related to PMs and their components. This comments list some limitations and perspectives about the associations of air pollution with health.

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.

TSPAN12 is a critical factor for cancer–fibroblast cell contact-mediated cancer invasion

PubMed Central

Otomo, Ryo; Otsubo, Chihiro; Matsushima-Hibiya, Yuko; Miyazaki, Makoto; Tashiro, Fumio; Ichikawa, Hitoshi; Kohno, Takashi; Ochiya, Takahiro; Yokota, Jun; Nakagama, Hitoshi; Taya, Yoichi; Enari, Masato

2014-01-01

Communication between cancer cells and their microenvironment controls cancer progression. Although the tumor suppressor p53 functions in a cell-autonomous manner, it has also recently been shown to function in a non–cell-autonomous fashion. Although functional defects have been reported in p53 in stromal cells surrounding cancer, including mutations in the p53 gene and decreased p53 expression, the role of p53 in stromal cells during cancer progression remains unclear. We herein show that the expression of α-smooth muscle actin (α-SMA), a marker of cancer-associated fibroblasts (CAFs), was increased by the ablation of p53 in lung fibroblasts. CAFs enhanced the invasion and proliferation of lung cancer cells when cocultured with p53-depleted fibroblasts and required contact between cancer and stromal cells. A comprehensive analysis using a DNA chip revealed that tetraspanin 12 (TSPAN12), which belongs to the tetraspanin protein family, was derepressed by p53 knockdown. TSPAN12 knockdown in p53-depleted fibroblasts inhibited cancer cell proliferation and invasion elicited by coculturing with p53-depleted fibroblasts in vitro, and inhibited tumor growth in vivo. It also decreased CXC chemokine ligand 6 (CXCL6) secretion through the β-catenin signaling pathway, suggesting that cancer cell contact with TSPAN12 in fibroblasts transduced β-catenin signaling into fibroblasts, leading to the secretion of CXCL6 to efficiently promote invasion. These results suggest that stroma-derived p53 plays a pivotal role in epithelial cancer progression and that TSPAN12 and CXCL6 are potential targets for lung cancer therapy. PMID:25512506

Association between lung function in school children and exposure to three transition metals from an e-waste recycling area.

PubMed

Zheng, Guina; Xu, Xijin; Li, Bin; Wu, Kusheng; Yekeen, Taofeek Akangbe; Huo, Xia

2013-01-01

The informal processing of electronic waste or e-waste contributes to the release of high concentrations of transition metals into the ambient air. The damage caused by chromium, nickel and manganese exposure on lung function in school children from an e-waste recycling area and the role of oxidative stress in this process were evaluated. We recruited school children (n=144, 8-13 years) from an e-waste recycling area in China compared with the control. Spirometry was performed to assess lung function status. The blood levels of chromium, nickel and manganese, antioxidant enzyme activities and lipid peroxidation of the subjects were examined. The concentrations of blood manganese (bMn) and serum nickel (sNi) in the exposed group were significantly higher than those in controls for all three age groups. The forced vital capacity value of boys aged 8-9 years was significantly lower than that of the control. Malondialdehyde levels and superoxide dismutase activities increased significantly in children aged 8-9 years from e-waste environment, but catalase activities declined. School children from an e-waste recycling area were exposed to high levels of the three transition metals. The accumulation of bMn and sNi may be risk factors for oxidative damage and decreased pulmonary function.

Setting individualized positive end-expiratory pressure level with a positive end-expiratory pressure decrement trial after a recruitment maneuver improves oxygenation and lung mechanics during one-lung ventilation.

PubMed

Ferrando, Carlos; Mugarra, Ana; Gutierrez, Andrea; Carbonell, Jose Antonio; García, Marisa; Soro, Marina; Tusman, Gerardo; Belda, Francisco Javier

2014-03-01

We investigated whether individualized positive end-expiratory pressure (PEEP) improves oxygenation, ventilation, and lung mechanics during one-lung ventilation compared with standardized PEEP. Thirty patients undergoing thoracic surgery were randomly allocated to the study or control group. Both groups received an alveolar recruitment maneuver at the beginning and end of one-lung ventilation. After the alveolar recruitment maneuver, the control group had their lungs ventilated with a 5 cm·H2O PEEP, while the study group had their lungs ventilated with an individualized PEEP level determined by a PEEP decrement trial. Arterial blood samples, lung mechanics, and volumetric capnography were recorded at multiple timepoints throughout the procedure. The individualized PEEP values in study group were higher than the standardized PEEP values (10 ± 2 vs 5 cm·H2O; P < 0.001). In both groups, arterial oxygenation decreased when bilateral-lung ventilation was switched to one-lung ventilation and increased after the alveolar recruitment maneuver. During one-lung ventilation, oxygenation was maintained in the study group but decreased in the control group. After one-lung ventilation, arterial oxygenation was significantly higher in the study group (306 vs 231 mm·Hg, P = 0.007). Static compliance decreased in both groups when bilateral-lung ventilation was switched to one-lung ventilation. Static compliance increased significantly only in the study group (P < 0.001) after the alveolar recruitment maneuver and optimal PEEP adjustment. The alveolar recruitment maneuver did not decrease cardiac index in any patient. During one-lung ventilation, the improvements in oxygenation and lung mechanics after an alveolar recruitment maneuver were better preserved by ventilation by using individualized PEEP with a PEEP decrement trial than with a standardized 5 cm·H2O of PEEP.

Achromobacter xylosoxidans infection in an adult cystic fibrosis unit in Madrid.

PubMed

Llorca Otero, Laura; Girón Moreno, Rosa; Buendía Moreno, Buenaventura; Valenzuela, Claudia; Guiu Martínez, Alba; Alarcón Cavero, Teresa

2016-03-01

Achromobacter xylosoxidans is an emerging pathogen in cystic fibrosis (CF). Although the rate of colonization by this microorganism is variable, prevalence is increasing in CF units. A microbiological/clinical study was conducted on of adult CF patients harboring A. xylosoxidans. Identification and susceptibility testing were performed using MicroScan (Siemens). Decline in lung function was assessed using the variable, annual percentage loss of FEV1 (forced expiratory volume in 1s). A. xylosoxidans was isolated in 18 (19.8%) of 91 patients over a 14-year period. Mean age was 26.6 years (18-39 years). Nine patients (9.8%) were chronically colonized. Piperacillin/tazobactam and imipenem were the most active antibiotics. Mean annual decline in lung function in chronically colonized patients was 2.49%. A. xylosoxidans is a major pathogen in CF. A decreased lung function was observed among patients who were chronically colonized by A. xylosoxidans. Antibiotic therapy should be started early in order to prevent chronic colonization by this microorganism. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Physiology of respiratory disturbances in muscular dystrophies

PubMed Central

Lo Mauro, Antonella

2016-01-01

Muscular dystrophy is a group of inherited myopathies characterised by progressive skeletal muscle wasting, including of the respiratory muscles. Respiratory failure, i.e. when the respiratory system fails in its gas exchange functions, is a common feature in muscular dystrophy, being the main cause of death, and it is a consequence of lung failure, pump failure or a combination of the two. The former is due to recurrent aspiration, the latter to progressive weakness of respiratory muscles and an increase in the load against which they must contract. In fact, both the resistive and elastic components of the work of breathing increase due to airway obstruction and chest wall and lung stiffening, respectively. The respiratory disturbances in muscular dystrophy are restrictive pulmonary function, hypoventilation, altered thoracoabdominal pattern, hypercapnia, dyspnoea, impaired regulation of breathing, inefficient cough and sleep disordered breathing. They can be present at different rates according to the type of muscular dystrophy and its progression, leading to different onset of each symptom, prognosis and degree of respiratory involvement. Key points A common feature of muscular dystrophy is respiratory failure, i.e. the inability of the respiratory system to provide proper oxygenation and carbon dioxide elimination. In the lung, respiratory failure is caused by recurrent aspiration, and leads to hypoxaemia and hypercarbia. Ventilatory failure in muscular dystrophy is caused by increased respiratory load and respiratory muscles weakness. Respiratory load increases in muscular dystrophy because scoliosis makes chest wall compliance decrease, atelectasis and fibrosis make lung compliance decrease, and airway obstruction makes airway resistance increase. The consequences of respiratory pump failure are restrictive pulmonary function, hypoventilation, altered thoracoabdominal pattern, hypercapnia, dyspnoea, impaired regulation of breathing, inefficient cough and sleep disordered breathing. Educational aims To understand the mechanisms leading to respiratory disturbances in patients with muscular dystrophy. To understand the impact of respiratory disturbances in patients with muscular dystrophy. To provide a brief description of the main forms of muscular dystrophy with their respiratory implications. PMID:28210319

Physiology of respiratory disturbances in muscular dystrophies.

PubMed

Lo Mauro, Antonella; Aliverti, Andrea

2016-12-01

Muscular dystrophy is a group of inherited myopathies characterised by progressive skeletal muscle wasting, including of the respiratory muscles. Respiratory failure, i.e . when the respiratory system fails in its gas exchange functions, is a common feature in muscular dystrophy, being the main cause of death, and it is a consequence of lung failure, pump failure or a combination of the two. The former is due to recurrent aspiration, the latter to progressive weakness of respiratory muscles and an increase in the load against which they must contract. In fact, both the resistive and elastic components of the work of breathing increase due to airway obstruction and chest wall and lung stiffening, respectively. The respiratory disturbances in muscular dystrophy are restrictive pulmonary function, hypoventilation, altered thoracoabdominal pattern, hypercapnia, dyspnoea, impaired regulation of breathing, inefficient cough and sleep disordered breathing. They can be present at different rates according to the type of muscular dystrophy and its progression, leading to different onset of each symptom, prognosis and degree of respiratory involvement. A common feature of muscular dystrophy is respiratory failure, i.e. the inability of the respiratory system to provide proper oxygenation and carbon dioxide elimination.In the lung, respiratory failure is caused by recurrent aspiration, and leads to hypoxaemia and hypercarbia.Ventilatory failure in muscular dystrophy is caused by increased respiratory load and respiratory muscles weakness.Respiratory load increases in muscular dystrophy because scoliosis makes chest wall compliance decrease, atelectasis and fibrosis make lung compliance decrease, and airway obstruction makes airway resistance increase.The consequences of respiratory pump failure are restrictive pulmonary function, hypoventilation, altered thoracoabdominal pattern, hypercapnia, dyspnoea, impaired regulation of breathing, inefficient cough and sleep disordered breathing. To understand the mechanisms leading to respiratory disturbances in patients with muscular dystrophy.To understand the impact of respiratory disturbances in patients with muscular dystrophy.To provide a brief description of the main forms of muscular dystrophy with their respiratory implications.

Impaired diversity of the lung microbiome predicts progression of idiopathic pulmonary fibrosis.

PubMed

Takahashi, Youhei; Saito, Atsushi; Chiba, Hirofumi; Kuronuma, Koji; Ikeda, Kimiyuki; Kobayashi, Tomofumi; Ariki, Shigeru; Takahashi, Motoko; Sasaki, Yasushi; Takahashi, Hiroki

2018-02-27

Idiopathic pulmonary fibrosis (IPF) is the most frequent and severe form of idiopathic interstitial pneumonias. Although IPF has not been thought to be associated with bacterial communities, recent papers reported the possible role of microbiome composition in IPF. The roles of microbiomes in respiratory functions and as clinical biomarkers for IPF remain unknown. In this study, we aim to identify the relationship between the microbial environment in the lung and clinical findings. Thirty-four subjects diagnosed with IPF were included in this analysis. The 16S rDNA was purified from bronchoalveolar lavage fluid obtained at the time of diagnosis and analyzed using next-generation sequencing techniques to characterize the bacterial communities. Furthermore, microbiomes from mice with bleomycin-induced lung fibrosis were analyzed. The most prevalent lung phyla were Firmicutes, Proteobacteria and Bacteroidetes. Decreased microbial diversity was found in patients with low forced vital capacity (FVC) and early mortality. Additionally, the diversity and relative abundance of Firmicutes, Streptococcaceae, and Veillonellaceae were significantly associated with FVC, 6-min walk distance, and serum surfactant protein D. Bleomycin-induced lung fibrosis resulted in decrease of diversity and alteration of microbiota in PCoA analysis. These results support the observations in human specimens. This study identified relationships between specific taxa in BALF and clinical findings, which were also supported by experiments in a mouse model. Our data suggest the possibility that loss of microbial diversity is associated with disease activities of IPF.

Effects of kefir on ischemia-reperfusion injury.

PubMed

Yener, A U; Sehitoglu, M H; Ozkan, M T A; Bekler, A; Ekin, A; Cokkalender, O; Deniz, M; Sacar, M; Karaca, T; Ozcan, S; Kurt, T

2015-01-01

We aimed to investigate the effect of kefir on Ischemia-Reperfusion (I/R) injury on rats. 24 male Sprague-Dawley rats between 250-350 g were selected. Rats were divided into three groups, and there were eight rats in each group. Rats were fed for 60 days. All of the rats were fed with the same diet for the first 30 days. In the second thirty days, kefir [10 cc/kg/day body weight (2 x 109 cfu/kg/day)] was added to the diet of the study group by gavage method. In all groups, lung and kidney tissues were removed after the procedure and rats were sacrificed. The biochemical and histopathological changes were observed in the lung and kidney within the samples. Serum urea, creatinine and tumor necrosis factor (TNF-α) were determined. Kefir + I/R groups was compared with I/R groups, a significant decrease (p < 0.05) was seen in Lipid peroxidation (MDA) levels of lung and renal tissues. Superoxide dismutase (SOD), Catalase (CAT) and Glutathione peroxidase (GSH-Px) activities of lung and kidney tissues decreased in I/R groups (p < 0.05). The enzyme activities in Kefir + I/R groups of renal tissues were significantly (p < 0.05) higher than I/R, not significantly different in lung tissues (p < 0.05). Kefir reduced the levels of serum urea, creatinine and TNF-α significantly.   This would be useful in this model against ischemia/reperfusion, and shows the protective effect of kefir in tissue and serum functions.

Pulmonary responses of healthy young adults exposed to 0.06 and 0.08 ppm ozone

EPA Science Inventory

Background. Previous studies have shown small but significant decreases in spirometric lung function in healthy young adults exposed to 0.08 ppm ozone. It is unclear, however, if such effects may are seen at concentrations below 0.08 ppm. Methods. A group of 30 healthy young adul...

Lung volumes during sustained microgravity on Spacelab SLS-1

NASA Technical Reports Server (NTRS)

Elliott, Ann R.; Prisk, Gordon Kim; Guy, Harold J. B.; West, John B.

1994-01-01

Gravity is known to influence the topographical gradients of pulmonary ventilation, perfusion, and pleural pressures. The effect of sustained microgravity on lung volumes has not previously been investigated. Pulmonary function tests were performed by four subjects before, during, and after 9 days of microgravity exposure. Ground measurements were made in standing and supine postures. Tests were performed using a bag-in-box and flowmeter system and a respiratory mass spectrometer. Measurements of tidal volume (V(sub T)), expiratory reserve volume (ERV), inspiratory and expiratory vital capacities (IVC, EVC), functional residual capacity (FRC), and residual volume (RV) were made. During microgravity, V(sub T) decreased by 15%. IVC and EVC were slightly reduced during the first 24 hrs of microgravity and returned to 1 g standing values within 72 hrs after the onset of microgravity. FRC was reduced by 15% and ERV decreased by 10-20%. RV was significantly reduced by 18%. The reductions in FRC, ERV, and V(sub T) during microgravity are probably due to the cranial shift of the diaphragm and an increase in intrathoracic blood volume.

[Pulmonary function in patients with focal pulmonary tuberculosis].

PubMed

Nefedov, V B; Popova, L A; Shergina, E A

2008-01-01

Vital capacity (VC), forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), FEV1/VC%, PEF, MEF25, MEF50, MEF75, TLC, TGV, pulmonary residual volume (PRV), Raw, Rin, Rcx, DLCO-SB, DLCO-SS/VA, PaO2, and PaCO2 were determined in 40 patients with focal pulmonary tuberculosis. Changes were found in lung volumes and capacities in 75%, impaired bronchial patency and pulmonary gas exchange dysfunction were in 57.5 and 25%, respectively. The lung volume and capacity changes appeared mainly as increased TGV and PRV; impaired bronchial patency presented as decreased MEF50, MEF75, and FEV1/VC%; pulmonary gas exchange dysfunction manifested itself as reduced DLCO-SB, PaO2, and PaCO2. The magnitude of the observed functional changes was generally slight. TGV and PRL increased up to 148-187 and 142-223% of the normal values, respectively; MEF50, MEF75, FEV1/VC%, and DLCO decreased to 59-24, 58-26, 78-57, and 78-67% of the normal values and PaO2 and PaCO2 did to 79-69 and 34-30 cm Hg.

Lung autophagic response following exposure of mice to whole body irradiation, with and without amifostine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zois, Christos E.; Giatromanolaki, Alexandra; Kainulainen, Heikki

2011-01-07

Research highlights: {yields} We investigated the effect 6 Gy of WBI on the autophagic machinery of normal mouse lung. {yields} Irradiation induces dysfunction of the autophagic machinery in normal lung, characterized by decreased transcription of the LC3A/Beclin-1 mRNA and accumulation of the LC3A, and p62 proteins. {yields} The membrane bound LC3A-II protein levels increased in the cytosolic fraction (not in the pellet), contrasting the patterns noted after starvation-induced autophagy. {yields} Administration of amifostine, reversed all the LC3A and p62 findings, suggesting protection of the normal autophagic function. -- Abstract: Purpose: The effect of ionizing irradiation on the autophagic response ofmore » normal tissues is largely unexplored. Abnormal autophagic function may interfere the protein quality control leading to cell degeneration and dysfunction. This study investigates its effect on the autophagic machinery of normal mouse lung. Methods and materials: Mice were exposed to 6 Gy of whole body {gamma}-radiation and sacrificed at various time points. The expression of MAP1LC3A/LC3A/Atg8, beclin-1, p62/sequestosome-1 and of the Bnip3 proteins was analyzed. Results: Following irradiation, the LC3A-I and LC3A-II protein levels increased significantly at 72 h and 7 days. Strikingly, LC3A-II protein was increased (5.6-fold at 7 days; p < 0.001) only in the cytosolic fraction, but remained unchanged in the membrane fraction. The p62 protein, was significantly increased in both supernatant and pellet fraction (p < 0.001), suggesting an autophagosome turnover deregulation. These findings contrast the patterns of starvation-induced autophagy up-regulation. Beclin-1 levels remained unchanged. The Bnip3 protein was significantly increased at 8 h, but it sharply decreased at 72 h (p < 0.05). Administration of amifostine (200 mg/kg), 30 min before irradiation, reversed all the LC3A and p62 findings on blots, suggesting restoration of the normal autophagic function. The LC3A and Beclin1 mRNA levels significantly declined following irradiation (p < 0.01), whereas Bnip3 levels increased. Conclusions: It is suggested that irradiation induces dysfunction of the autophagic machinery in normal lung, characterized by decreased transcription of the LC3A/Beclin-1 mRNA and accumulation of the LC3A, and p62 proteins. Whether this is due to defective maturation or to aberrant degradation of the autophagosomes requires further investigation.« less

Overexpression of microRNA‑125a‑3p effectively inhibits the cell growth and invasion of lung cancer cells by regulating the mouse double minute 2 homolog/p53 signaling pathway.

PubMed

Li, Shenglei; Li, Xin; Zhao, Huasi; Gao, Ming; Wang, Feng; Li, Wencai

2015-10-01

MicroRNAs (miRs) are a family of small non-coding RNAs that are 21‑24 nucleotides in length. Decreased expression of hsa‑miR‑125a‑3p is observed in a number of patients with non‑small cell lung cancer; however, it is not clear how this miRNA regulates the growth and invasion of lung tumor cells. The aim of the present study was to identify the function of hsa‑miR‑125a‑3p in the growth and invasion of lung cancer cells. The expression of hsa‑miR‑125a‑3p in the A549, NCI‑H460 and SPCA‑1 lung cancer cell lines was analyzed by reverse transcription‑quantitative polymerase chain reaction and the human bronchiolar epithelium cell line (HBE) was used as a control. The results demonstrated that the expression of hsa‑miR‑125a‑3p was significantly lower in NCI‑H460, A549 and SPCA‑1 cells, compared with that in HBE cells. Overexpression of sense miR‑125a‑3p in the A549 lung cancer cell line inhibited cell proliferation for 5‑7 days (P<0.01), and transfection of antisense miR‑125a‑3p did not suppress the cell growth of the lung cancer cells. In addition, overexpression of miR‑125a‑3p in the NCI‑H460 lung cancer cell line markedly induced cell apoptosis, which was detected by fluorescence‑activated cell sorting with annexin V‑fluorescein isothiocyanate/propidium iodide staining. The results of the Transwell migration assay also revealed that transfection of miR‑125a‑3p resulted in decreased migration of lung cancer tumor cells. The pro‑apoptotic gene p53 expression was detected by western blot analysis. The results revealed that the expression of mouse double minute (MDM)‑2 homolog, the principal cellular antagonist of p53, was decreased and p53 expression was upregulated in sense has‑miR‑125a‑3p transfected A549 cells. This was consistent with that observed in NCI‑H460 cells, suggesting that hsa‑miR‑125a‑3p may be involved in the regulation of the MDM2/p53 signaling pathway in lung cancer cells. In conclusion, overexpression of hsa‑miR‑125a‑3p significantly inhibited the proliferation and invasion of lung cancer cells, which may aid in determining the mechanisms underlying the development of lung cancer.

Lung lavage with oxygenated perfluorochemical liquid in acute lung injury.

PubMed

Richman, P S; Wolfson, M R; Shaffer, T H

1993-05-01

To investigate the effects of lung lavage with oxygenated liquid perfluorochemical on gas exchange, lung mechanics, and cardiac function in animals with acute lung injury. Prospective, randomized, controlled trial. Animal laboratory. Eight adult cats (2 to 4 kg, random sex). Two insults were combined to cause lung injury: oleic acid infusion and saline whole-lung wash. Animals were assigned to either the control or treatment group which consisted of a perfluorochemical liquid (Rimar 101) lavage. Perfluorochemical liquid lavage was performed three times at hourly intervals after lung injury. Three other cats with identical injury but no perfluorochemical liquid lavage served as control animals. All cats were ventilated with an FIO2 of 0.95 and positive end-expiratory pressure of 2 cm H2O continuously. Arterial blood gas tensions and pH, dynamic pulmonary compliance were measured at 15-min intervals. Cardiac index was assessed hourly, and lung fluid was collected after each of the three perfluorochemical liquid lavages. Arterial oxygen tension and pulmonary compliance deteriorated abruptly after lung injury in all cats, and improved significantly (p < .001, two-way analysis of variance) 15 mins after perfluorochemical liquid lavage. These parameters gradually returned to their baseline over 60 mins. Arterial blood pressure and cardiac index decreased after injury in all cats, and were not significantly changed after perfluorochemical liquid lavage. Hemorrhagic fluid was recovered from distal airways by perfluorochemical liquid lavage, despite prior suctioning of the airway. Perfluorochemical liquid lavage removes pulmonary edema fluid and improves gas exchange and the mechanical properties of the lung, after acute severe lung injury.

Slow loaded breathing training improves blood pressure, lung capacity and arm exercise endurance for older people with treated and stable isolated systolic hypertension.

PubMed

Ublosakka-Jones, Chulee; Tongdee, Phailin; Pachirat, Orathai; Jones, David A

2018-03-28

Hypertension and reduced lung function are important features of aging. Slow loaded breathing training reduces resting blood pressure and the question is whether this can also improve lung function. Thirty-two people (67 ± 5 years, 16 male) with controlled isolated systolic hypertension undertook an eight weeks randomised controlled training trial with an inspiratory load of 25% maximum inspiratory pressure (MIP) at 6 breaths per minute (slow loaded breathing; SLB) or deep breathing control (CON). Outcome measures were resting blood pressure (BP) and heart rate; MIP; lung capacity; chest and abdominal expansion; arm cranking exercise endurance at 50% heart rate reserve. Home based measurement of resting systolic BP decreased by 20 mm Hg (15 to 25) (Mean and 95%CI) for SLB and by 5 mm Hg (1 to 7) for CON. Heart rate and diastolic BP also decreased significantly for SLB but not CON. MIP increased by 15.8 cm H 2 O (11.8 to 19.8) and slow vital capacity by 0.21 L (0.15 to 0.27) for SLB but not for CON. Chest and abdominal expansion increased by 2.3 cm (2.05 to 2.55) and 2.5 cm (2.15 to 2.85), respectively for SLB and by 0.5 cm (0.26 to 0.74) and 1.7 cm (1.32 to 2.08) for CON. Arm exercise time increased by 4.9 min (3.65 to 5.15) for SLB with no significant change for CON. Slow inspiratory muscle training is not only effective in reducing resting BP, even in older people with well controlled isolated systolic hypertension but also increases inspiratory muscle strength, lung capacity and arm exercise duration. Copyright © 2018. Published by Elsevier Inc.

Maternal exposure to fine particulate air pollution induces epithelial-to-mesenchymal transition resulting in postnatal pulmonary dysfunction mediated by transforming growth factor-β/Smad3 signaling.

PubMed

Tang, Wenting; Du, Lili; Sun, Wen; Yu, Zhiqiang; He, Fang; Chen, Jingsi; Li, Xiaomei; Li, Xiuying; Yu, Lin; Chen, Dunjin

2017-02-05

Fine particles from air pollution, also called particulate matter, less than 2.5 micrometers in diameter (PM2.5), are a threat to child health. Epidemiological investigations have related maternal exposure to PM2.5 to postnatal respiratory symptoms, such as frequent wheezing, chronic cough, and lung function decrements. However, only few experimental animal studies have been performed to study the effects of PM2.5.The aim of this study was to investigate the effects of maternal exposure to PM2.5 on postnatal pulmonary dysfunction in a rat model and to examine the mechanism of PM2.5-induced morphological pulmonary changes.Timed pregnant Sprague-Dawley rats were treated with PM2.5 (0.1, 0.5, 2.5, or 7.5mg/kg) once every three days from day 0 to 18 of pregnancy. After delivery, pups were sacrificed on postnatal day (PND)1 and 28. The effects of transforming growth factor-beta (TGF-β) on epithelial-mesenchymal transition (EMT) were determined by immunohistochemistry, Western blotting, and quantitative RT-PCR. The offspring underwent pulmonary function measurements on PND28, lung tissues were histopathologically examined, and markers of oxidative stress were measured. Maternally PM2.5-exposed offspring pups displayed significant decreases in lung volume parameters, compliance, and airflow during expiration on PND28. The PM2.5-exposed group showed interstitial proliferation in lung histology, significant oxidative stress in lungs, and up-regulation of TGF-β-induced EMT via increased vimentin and α-smooth muscle actin and decreased E-cadherin levels on PND1 and PND28.These results suggest that EMT up-regulation mediated by the TGF-β/Smad3 pathway plays a role in postnatal pulmonary dysfunction associated with maternal exposure to PM2.5. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Deleterious impact of hyperglycemia on cystic fibrosis airway ion transport and epithelial repair.

PubMed

Bilodeau, Claudia; Bardou, Olivier; Maillé, Émilie; Berthiaume, Yves; Brochiero, Emmanuelle

2016-01-01

Cystic fibrosis (CF)-related diabetes (CFRD) is associated with faster pulmonary function decline. Thus, we evaluated the impact of hyperglycemia on airway epithelial repair and transepithelial ion transport, which are critical in maintaining lung integrity and function. Non-CF and CF airway epithelial cells were exposed to low (LG) or high (HG) glucose before ion current and wound repair rate measurements. CFTR and K+ currents decreased after HG treatments. HG also reduced the wound healing rates of non-CF and CF cell monolayers. Although CFTR correction with VRT-325 accelerated the healing rates of CF cells monolayers under LG conditions, this improvement was significantly abrogated under HG conditions. Our data highlights a deleterious impact of hyperglycemia on ion transport and epithelial repair functions, which could contribute to the deterioration in lung function in CFRD patients. HG may also interfere with the beneficial effects of CFTR rescue on airway epithelial repair. Copyright © 2015 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

A prototype of volume-controlled tidal liquid ventilator using independent piston pumps.

PubMed

Robert, Raymond; Micheau, Philippe; Cyr, Stéphane; Lesur, Olivier; Praud, Jean-Paul; Walti, Hervé

2006-01-01

Liquid ventilation using perfluorochemicals (PFC) offers clear theoretical advantages over gas ventilation, such as decreased lung damage, recruitment of collapsed lung regions, and lavage of inflammatory debris. We present a total liquid ventilator designed to ventilate patients with completely filled lungs with a tidal volume of PFC liquid. The two independent piston pumps are volume controlled and pressure limited. Measurable pumping errors are corrected by a programmed supervisor module, which modifies the inserted or withdrawn volume. Pump independence also allows easy functional residual capacity modifications during ventilation. The bubble gas exchanger is divided into two sections such that the PFC exiting the lungs is not in contact with the PFC entering the lungs. The heating system is incorporated into the metallic base of the gas exchanger, and a heat-sink-type condenser is placed on top of the exchanger to retrieve PFC vapors. The prototype was tested on 5 healthy term newborn lambs (<5 days old). The results demonstrate the efficiency and safety of the prototype in maintaining adequate gas exchange, normal acido-basis equilibrium, and cardiovascular stability during a short, 2-hour total liquid ventilator. Airway pressure, lung volume, and ventilation scheme were maintained in the targeted range.

Aerosol-administered alpha-tocopherol attenuates lung inflammation in rats given lipopolysaccharide intratracheally.

PubMed

Hybertson, Brooks M; Chung, Jin H; Fini, Mehdi A; Lee, Young M; Allard, Jenny D; Hansen, Brian N; Cho, Okyong J; Shibao, Gayle N; Repine, John E

2005-04-01

Intrapulmonary administration of bacterial lipopolysaccharide (LPS) induces a well-characterized lung inflammatory response involving alveolar macrophage activation, proinflammatory cytokine elaboration, and neutrophil influx. Vitamin E, a lipophilic antioxidant consisting of a family that includes tocopherols and tocotrienols, has previously been shown to have a variety of anti-inflammatory effects, raising interest in its possible uses in disease prevention or therapy. Because aerosol delivery is a specific and rapid way to administer agents to the lungs, the authors undertook to determine whether inhaled vitamin E aerosols would have an anti-inflammatory effect in the lungs. Using a rat model of acute lung inflammation caused by intratracheally administered LPS (10 microg Pseudomonas aeruginosa LPS), the authors examined the effect of aerosol-administered vitamin E, in this case alpha-tocopherol, on several indices of lung inflammation which are increased by LPS treatment. It was found that inhaled alpha-tocopherol aerosol, but not inhaled alpha-tocopherol acetate aerosol, decreased tumor necrosis factor alpha (TNFalpha) and cytokine-induced neutrophil chemoattractant-1 (CINC-1) mRNA levels in lung tissue, TNFalpha and CINC-1 immunoreactive protein levels in lung lavage, and the number of neutrophils recoverable by lung lavage from rats given LPS intratracheally. These results contribute to the increasing body of work describing immunomodulatory functions of alpha-tocopherol, and support the idea that direct aerosol administration of alpha-tocopherol may play a beneficial role in strategies to control inflammatory lung illnesses.

Cystic Fibrosis Transmembrane Conductance Regulator Controls Lung Proteasomal Degradation and Nuclear Factor-κB Activity in Conditions of Oxidative Stress

PubMed Central

Boncoeur, Emilie; Roque, Telma; Bonvin, Elise; Saint-Criq, Vinciane; Bonora, Monique; Clement, Annick; Tabary, Olivier; Henrion-Caude, Alexandra; Jacquot, Jacky

2008-01-01

Cystic fibrosis is a lethal inherited disorder caused by mutations in a single gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein, resulting in progressive oxidative lung damage. In this study, we evaluated the role of CFTR in the control of ubiquitin-proteasome activity and nuclear factor (NF)-κB/IκB-α signaling after lung oxidative stress. After a 64-hour exposure to hyperoxia-mediated oxidative stress, CFTR-deficient (cftr−/−) mice exhibited significantly elevated lung proteasomal activity compared with wild-type (cftr+/+) animals. This was accompanied by reduced lung caspase-3 activity and defective degradation of NF-κB inhibitor IκB-α. In vitro, human CFTR-deficient lung cells exposed to oxidative stress exhibited increased proteasomal activity and decreased NF-κB-dependent transcriptional activity compared with CFTR-sufficient lung cells. Inhibition of the CFTR Cl− channel by CFTRinh-172 in the normal bronchial immortalized cell line 16HBE14o− increased proteasomal degradation after exposure to oxidative stress. Caspase-3 inhibition by Z-DQMD in CFTR-sufficient lung cells mimicked the response profile of increased proteasomal degradation and reduced NF-κB activity observed in CFTR-deficient lung cells exposed to oxidative stress. Taken together, these results suggest that functional CFTR Cl− channel activity is crucial for regulation of lung proteasomal degradation and NF-κB activity in conditions of oxidative stress. PMID:18372427

Maresin 1 Ameliorates Lung Ischemia/Reperfusion Injury by Suppressing Oxidative Stress via Activation of the Nrf-2-Mediated HO-1 Signaling Pathway

PubMed Central

Wu, You; Zhao, Feng

2017-01-01

Lung ischemia/reperfusion (I/R) injury occurs in various clinical conditions and heavily damaged lung function. Oxidative stress reaction and antioxidant enzymes play a pivotal role in the etiopathogenesis of lung I/R injury. In the current study, we investigated the impact of Maresin 1 on lung I/R injury and explored the possible mechanism involved in this process. MaR 1 ameliorated I/R-induced lung injury score, wet/dry weight ratio, myeloperoxidase, tumor necrosis factor, bronchoalveolar lavage fluid (BALF) leukocyte count, BALF neutrophil ratio, and pulmonary permeability index levels in lung tissue. MaR 1 significantly reduced ROS, methane dicarboxylic aldehyde, and 15-F2t-isoprostane generation and restored antioxidative enzyme (superoxide dismutase, glutathione peroxidase, and catalase) activities. Administration of MaR 1 improved the expression of nuclear Nrf-2 and cytosolic HO-1 in I/R-treated lung tissue. Furthermore, we also found that the protective effects of MaR 1 on lung tissue injury and oxidative stress were reversed by HO-1 activity inhibitor, Znpp-IX. Nrf-2 transcription factor inhibitor, brusatol, significantly decreased MaR 1-induced nuclear Nrf-2 and cytosolic HO-1 expression. In conclusion, these results indicate that MaR 1 protects against lung I/R injury through suppressing oxidative stress. The mechanism is partially explained by activation of the Nrf-2-mediated HO-1 signaling pathway. PMID:28751936

Ethyl pyruvate reduces acute lung damage following trauma and hemorrhagic shock via inhibition of NF-κB and HMGB1.

PubMed

Relja, Borna; Wagner, Nils; Franz, Niklas; Dieteren, Scott; Mörs, Katharina; Schmidt, Julia; Marzi, Ingo; Perl, Mario

2018-03-01

After blunt thoracic trauma (TxT) and hemorrhagic shock with resuscitation (H/R) intense local inflammatory response and cell loss frequently impair the pulmonary function. Ethyl pyruvate (EP) has been reported to improve the pathophysiologic derangements in models of acute inflammation. Here, we studied the effects of EP on inflammation and lung damage after TxT+H/R. Twenty four female Lewis rats (180-240g) were randomly divided into 3 groups: two groups underwent TxT followed by hemorrhagic shock (35±3mmHg) for 60min and resuscitation with either Ringers-Lactat (RL) alone or RL supplemented with EP (EP, 50mg/kg). Sham operated animals underwent surgical procedures. Two hours later bronchoalveolar lavage fluid (BAL), lung tissue and blood were collected for analyses. EP significantly improved pO 2 levels compared to RL after TxT+H/R. TxT+H/R induced elevated levels of lactate dehydrogenase, total protein concentration in BAL and lung damage as evidenced by lung histology; these effects were significantly reduced by EP. Local inflammatory markers, lung TNF-alpha protein levels and infiltration with polymorphonuclear leukocytes (PMNL) significantly decreased in EP vs. RL group after TxT+H/R. Indicators of apoptosis as reduced BCL-2 and increased FAS gene expression after TxT+H/R were significantly increased or decreased, respectively, by EP after TxT+H/R. EP reduced TxT+H/R-induced p65 phosphorylation, which was concomitant with reduced HMGB1 levels in lung sections. Taken together, TxT+H/R induced strong inflammatory response and apoptotic changes as well as lung injury which were markedly diminished by EP. Our results suggest that this might be mediated via NF-κB and/or HMGB1 dependent mechanism. Copyright © 2017 Elsevier GmbH. All rights reserved.

Lung function in retired coke oven plant workers.

PubMed Central

Chau, N; Bertrand, J P; Guenzi, M; Mayer, L; Téculescu, D; Mur, J M; Patris, A; Moulin, J J; Pham, Q T

1992-01-01

Lung function was studied in 354 coke oven plant workers in the Lorraine collieries (Houillères du Bassin de Lorraine, France) who retired between 1963 and 1982 and were still alive on 1 January 1988. A spirometric examination was performed on 68.4% of them in the occupational health service. Occupational exposure to respiratory hazards throughout their career was retraced for each subject. No adverse effect of occupational exposure on ventilatory function was found. Ventilatory function was, however negatively linked with smoking and with the presence of a respiratory symptom or discrete abnormalities visible on pulmonary x ray films. The functional values were mostly slightly lower than predicted values and the most reduced index was the mean expiratory flow, FEF25-75%. The decrease in forced expiratory volume in one second (FEV1) was often parallel to that in forced vital capacity (FVC), but it was more pronounced for subjects who had worked underground, for smokers of more than 30 pack-years, and for subjects having a respiratory symptom. Pulmonary function indices were probably overestimated because of the exclusion of deceased subjects and the bias of the participants. PMID:1599869

Connective tissue-activating peptide III: a novel blood biomarker for early lung cancer detection.

PubMed

Yee, John; Sadar, Marianne D; Sin, Don D; Kuzyk, Michael; Xing, Li; Kondra, Jennifer; McWilliams, Annette; Man, S F Paul; Lam, Stephen

2009-06-10

There are no reliable blood biomarkers to detect early lung cancer. We used a novel strategy that allows discovery of differentially present proteins against a complex and variable background. Mass spectrometry analyses of paired pulmonary venous-radial arterial blood from 16 lung cancer patients were applied to identify plasma proteins potentially derived from the tumor microenvironment. Two differentially expressed proteins were confirmed in 64 paired venous-arterial blood samples using an immunoassay. Twenty-eight pre- and postsurgical resection peripheral blood samples and two independent, blinded sets of plasma from 149 participants in a lung cancer screening study (49 lung cancers and 100 controls) and 266 participants from the National Heart Lung and Blood Institute Lung Health Study (45 lung cancer and 221 matched controls) determined the accuracy of the two protein markers to detect subclinical lung cancer. Connective tissue-activating peptide III (CTAP III)/ neutrophil activating protein-2 (NAP-2) and haptoglobin were identified to be significantly higher in venous than in arterial blood. CTAP III/NAP-2 levels decreased after tumor resection (P = .01). In two independent population cohorts, CTAP III/NAP-2 was significantly associated with lung cancer and improved the accuracy of a lung cancer risk prediction model that included age, smoking, lung function (FEV(1)), and an interaction term between FEV(1) and CTAP III/NAP-2 (area under the curve, 0.84; 95% CI, 0.77 to 0.91) compared to CAPIII/NAP-2 alone. We identified CTAP III/NAP-2 as a novel biomarker to detect preclinical lung cancer. The study underscores the importance of applying blood biomarkers as part of a multimodal lung cancer risk prediction model instead of as stand-alone tests.

Persistent lung oscillator response to CO2 after buccal oscillator inhibition in the adult frog.

PubMed

Leclère, Renaud; Straus, Christian; Similowski, Thomas; Bodineau, Laurence; Fiamma, Marie-Noëlle

2012-08-15

The automatic ventilatory drive in amphibians depends on two oscillators interacting with each other, the gill/buccal and lung oscillators. The lung oscillator would be homologous to the mammalian pre-Bötzinger complex and the gill/buccal oscillator homologous to the mammalian parafacial respiratory group/retrotrapezoid nucleus (pFRG/RTN). Dysfunction of the pFRG/RTN has been involved in the development of respiratory diseases associated to the loss of CO(2) chemosensitivity such as the congenital central hypoventilation syndrome. Here, on adult in vitro isolated frog brainstem, consequences of the buccal oscillator inhibition (by reducing Cl(-)) were evaluated on the respiratory rhythm developed by the lung oscillator under hypercapnic challenges. Our results show that under low Cl(-) concentration (i) the buccal oscillator is strongly inhibited and the lung burst frequency and amplitude decreased and (ii) it persists a powerful CO(2) chemosensitivity. In conclusion, in frog, the CO(2) chemosensitivity depends on cellular contingent(s) whose the functioning is independent of the concentration of Cl(-) and origin remains unknown. Copyright © 2012 Elsevier B.V. All rights reserved.

Antioxidative, anti-inflammation and lung-protective effects of mycelia selenium polysaccharides from Oudemansiella radicata.

PubMed

Gao, Zheng; Li, Juan; Song, Xinling; Zhang, Jianjun; Wang, Xiuxiu; Jing, Huijuan; Ren, Zhenzhen; Li, Shangshang; Zhang, Chen; Jia, Le

2017-11-01

The present work was designed to investigated the antioxidant, anti-inflammation, and pulmonary protective effects of SMPS and MPS from Oudemansiella radicata on LPS-induced lung injured mice. The results demonstrated that SMPS showed potential effects on relieving lung injury and preventing oxidative stress, reflecting by decreasing the serum levels of C3, CRP and GGT, increasing the pulmonary activities of SOD, GSH-Px, CAT and T-AOC, as well as down-regulating the MDA and LPO contents, respectively. Furthermore, the levels of TNF-α (224.211±3.12ng/mL), IL-1β (254.557±2.18ng/L), and IL-6 (18.214±0.15ng/L) in BALF of mice treated with SMPS at the dosage of 400mg/kg/d significantly lower than that in the lung injured mice. These conclusions indicated that both SMPS and MPS possessed potent antioxidants and anti-inflammation activities, and could be used as functional foods and natural drugs in preventing lung injury. Copyright © 2017 Elsevier B.V. All rights reserved.

[Comparative studies on toxicity of various dielectrics, petroleum derivatives, used in electroerosion technology. IV. Morphological and cytoenzymatic changes in the lungs and acid-base imbalance in rats chronically exposed to petroleum hydrocarbons].

PubMed

Starek, A; Kamiński, M

1981-01-01

In rats exposed to odourless kerosene of 75 and 300 mg/m3 concentration, for 14 weeks, morphologic and cytoenzymatic examinations of lungs have been carried out and acid-base equilibrium indices in blood have been determined. Passive congestion of lung parenchyma, subpleural blood extravasation, atelectasis foci, thickened interalveolar septa with infiltrates from neutrophils, lymphocytes, eosinophils and macrophages have been found. In addition a decrease in succinic dehydrogenase activity, NADPH -- tetrazolium reductase, and Mg++-ATP-ase and increase in acid phosphatase activity have been revealed. Those have been focal changes, involving, apart from bronchial tree (low exposure -- 75 mg/m3), the remaining lung parenchyma segments (high exposure -- 300 mg/m3). In addition, disturbances in acid-base equilibrium in form of compensated metabolic alkalosis (75 mg/m3) and compensated metabolic acidosis (300 mg/m3) have occurred. The obtained results demonstrate toxic effects of kerosene hydrocarbons on the function and structure of lungs.

The Evolution of Unidirectional Pulmonary Airflow.

PubMed

Farmer, C G

2015-07-01

Conventional wisdom holds that the avian respiratory system is unique because air flows in the same direction through most of the gas-exchange tubules during both phases of ventilation. However, recent studies showing that unidirectional airflow also exists in crocodilians and lizards raise questions about the true phylogenetic distribution of unidirectional airflow, the selective drivers of the trait, the date of origin, and the functional consequences of this phenomenon. These discoveries suggest unidirectional flow was present in the common diapsid ancestor and are inconsistent with the traditional paradigm that unidirectional flow is an adaptation for supporting high rates of gas exchange. Instead, these discoveries suggest it may serve functions such as decreasing the work of breathing, decreasing evaporative respiratory water loss, reducing rates of heat loss, and facilitating crypsis. The divergence in the design of the respiratory system between unidirectionally ventilated lungs and tidally ventilated lungs, such as those found in mammals, is very old, with a minimum date for the divergence in the Permian Period. From this foundation, the avian and mammalian lineages evolved very different respiratory systems. I suggest the difference in design is due to the same selective pressure, expanded aerobic capacity, acting under different environmental conditions. High levels of atmospheric oxygen of the Permian Period relaxed selection for a thin blood-gas barrier and may have resulted in the homogeneous, broncho-alveolar design, whereas the reduced oxygen of the Mesozoic selected for a heterogeneous lung with an extremely thin blood-gas barrier. These differences in lung design may explain the puzzling pattern of ecomorphological diversification of Mesozoic mammals: all were small animals that did not occupy niches requiring a great aerobic capacity. The broncho-alveolar lung and the hypoxia of the Mesozoic may have restricted these mammals from exploiting niches of large body size, where cursorial locomotion can be advantageous, as well as other niches requiring great aerobic capacities, such as those using flapping flight. Furthermore, hypoxia may have exerted positive selection for a parasagittal posture, the diaphragm, and reduced erythrocyte size, innovations that enabled increased rates of ventilation and more rapid rates of diffusion in the lung. ©2015 Int. Union Physiol. Sci./Am. Physiol. Soc.

Pulmonary CCR2+CD4+ T cells are immune regulatory and attenuate lung fibrosis development.

PubMed

Milger, Katrin; Yu, Yingyan; Brudy, Eva; Irmler, Martin; Skapenko, Alla; Mayinger, Michael; Lehmann, Mareike; Beckers, Johannes; Reichenberger, Frank; Behr, Jürgen; Eickelberg, Oliver; Königshoff, Melanie; Krauss-Etschmann, Susanne

2017-11-01

Animal models have suggested that CCR2-dependent signalling contributes to the pathogenesis of pulmonary fibrosis, but global blockade of CCL2 failed to improve the clinical course of patients with lung fibrosis. However, as levels of CCR2 + CD4 + T cells in paediatric lung fibrosis had previously been found to be increased, correlating with clinical symptoms, we hypothesised that distinct CCR2 + cell populations might either increase or decrease disease pathogenesis depending on their subtype. To investigate the role of CCR2 + CD4 + T cells in experimental lung fibrosis and in patients with idiopathic pulmonary fibrosis and other fibrosis. Pulmonary CCR2 + CD4 + T cells were analysed using flow cytometry and mRNA profiling, followed by in silico pathway analysis, in vitro assays and adoptive transfer experiments. Frequencies of CCR2 + CD4 + T cells were increased in experimental fibrosis-specifically the CD62L - CD44 + effector memory T cell phenotype, displaying a distinct chemokine receptor profile. mRNA profiling of isolated CCR2 + CD4 + T cells from fibrotic lungs suggested immune regulatory functions, a finding that was confirmed in vitro using suppressor assays. Importantly, adoptive transfer of CCR2 + CD4 + T cells attenuated fibrosis development. The results were partly corroborated in patients with lung fibrosis, by showing higher percentages of Foxp3 + CD25 + cells within bronchoalveolar lavage fluid CCR2 + CD4 + T cells as compared with CCR2 - CD4 + T cells. Pulmonary CCR2 + CD4 + T cells are immunosuppressive, and could attenuate lung inflammation and fibrosis. Therapeutic strategies completely abrogating CCR2-dependent signalling will therefore also eliminate cell populations with protective roles in fibrotic lung disease. This emphasises the need for a detailed understanding of the functions of immune cell subsets in fibrotic lung disease. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

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

PubMed Central

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

2014-01-01

Rationale: Occupational exposure to indium compounds, including indium–tin oxide, can result in potentially fatal indium lung disease. However, the early effects of exposure on the lungs are not well understood. Objectives: To determine the relationship between short-term occupational exposures to indium compounds and the development of early lung abnormalities. Methods: Among indium–tin oxide production and reclamation facility workers, we measured plasma indium, respiratory symptoms, pulmonary function, chest computed tomography, and serum biomarkers of lung disease. Relationships between plasma indium concentration and health outcome variables were evaluated using restricted cubic spline and linear regression models. Measurements and Main Results: Eighty-seven (93%) of 94 indium–tin oxide facility workers (median tenure, 2 yr; median plasma indium, 1.0 μg/l) participated in the study. Spirometric abnormalities were not increased compared with the general population, and few subjects had radiographic evidence of alveolar proteinosis (n = 0), fibrosis (n = 2), or emphysema (n = 4). However, in internal comparisons, participants with plasma indium concentrations ≥ 1.0 μg/l had more dyspnea, lower mean FEV1 and FVC, and higher median serum Krebs von den Lungen-6 and surfactant protein-D levels. Spline regression demonstrated nonlinear exposure response, with significant differences occurring at plasma indium concentrations as low as 1.0 μg/l compared with the reference. Associations between health outcomes and the natural log of plasma indium concentration were evident in linear regression models. Associations were not explained by age, smoking status, facility tenure, or prior occupational exposures. Conclusions: In indium–tin oxide facility workers with short-term, low-level exposure, plasma indium concentrations lower than previously reported were associated with lung symptoms, decreased spirometric parameters, and increased serum biomarkers of lung disease. PMID:25295756

Genetic variation predicting cisplatin cytotoxicity associated with overall survival in lung cancer patients receiving platinum-based chemotherapy †, ‡

PubMed Central

Tan, Xiang-Lin; Moyer, Ann M.; Fridley, Brooke L.; Schaid, Daniel J.; Niu, Nifang; Batzler, Anthony J.; Jenkins, Gregory D.; Abo, Ryan P.; Li, Liang; Cunningham, Julie M.; Sun, Zhifu; Yang, Ping; Wang, Liewei

2011-01-01

Purpose Inherited variability in the prognosis of lung cancer patients treated with platinum-based chemotherapy has been widely investigated. However, the overall contribution of genetic variation to platinum response is not well established. To identify novel candidate SNPs/genes, we performed a genome-wide association study (GWAS) for cisplatin cytotoxicity using lymphoblastoid cell lines (LCLs), followed by an association study of selected SNPs from the GWAS with overall survival (OS) in lung cancer patients. Experimental Design GWAS for cisplatin were performed with 283 ethnically diverse LCLs. 168 top SNPs were genotyped in 222 small cell and 961 non-small cell lung cancer (SCLC, NSCLC) patients treated with platinum-based therapy. Association of the SNPs with OS was determined using the Cox regression model. Selected candidate genes were functionally validated by siRNA knockdown in human lung cancer cells. Results Among 157 successfully genotyped SNPs, 9 and 10 SNPs were top SNPs associated with OS for patients with NSCLC and SCLC, respectively, although they were not significant after adjusting for multiple testing. Fifteen genes, including 7 located within 200 kb up or downstream of the four top SNPs and 8 genes for which expression was correlated with three SNPs in LCLs were selected for siRNA screening. Knockdown of DAPK3 and METTL6, for which expression levels were correlated with the rs11169748 and rs2440915 SNPs, significantly decreased cisplatin sensitivity in lung cancer cells. Conclusions This series of clinical and complementary laboratory-based functional studies identified several candidate genes/SNPs that might help predict treatment outcomes for platinum-based therapy of lung cancer. PMID:21775533

Evaluation of role of Notch3 signaling pathway in human lung cancer cells.

PubMed

Hassan, Wael Abdo; Yoshida, Ryoji; Kudoh, Shinji; Motooka, Yamato; Ito, Takaaki

2016-05-01

There is still a debate on the extent to which Notch3 signaling is involved in lung carcinogenesis and whether such function is dependent on cancer type or not. To evaluate Notch3 expression in different types of human lung cancer cells. Notch3 was detected in human lung cancer cell lines and in tissues. Then, small interfering RNA (siRNA) was used to down-regulate the expression of Notch3 in H69AR small cell lung carcinoma (SCLC) cells; two non-small cell lung carcinoma (NSCLC) cells; A549 adenocarcinoma (ADC); and H2170 squamous cell carcinoma (SCC). In addition, Notch3 intracellular domain (N3ICD) plasmid was transfected into H1688 human SCLC cells. We observed the effect of deregulating Notch3 signaling on the following cell properties: Notch-related proteins, cell morphology, adhesion, epithelial-mesenchymal transition (EMT), motility, proliferation and neuroendocrine (NE) features of SCLC. Notch3 is mainly expressed in NSCLC, and the expression of Notch1, Hes1 and Jagged1 is affected by Notch3. Notch3 has opposite functions in SCLC and NSCLC, being a tumor suppressor in the former and tumor promoting in the latter, in the context of cell adhesion, EMT and motility. Regarding cell proliferation, we found that inhibiting Notch3 in NSCLC decreases cell proliferation and induces apoptosis in NSCLC. Notch3 has no effect on cell proliferation or NE features of SCLC. Notch3 signaling in lung carcinoma is dependent on cell type. In SCLC, Notch3 behaves as a tumor suppressor pathway, while in NSCLC it acts as a tumor-promoting pathway.

Grape seed extract ameliorates bleomycin-induced mouse pulmonary fibrosis.

PubMed

Liu, Qi; Jiang, Jun-Xia; Liu, Ya-Nan; Ge, Ling-Tian; Guan, Yan; Zhao, Wei; Jia, Yong-Liang; Dong, Xin-Wei; Sun, Yun; Xie, Qiang-Min

2017-05-05

Pulmonary fibrosis is common in a variety of inflammatory lung diseases, such as interstitial pneumonia, chronic obstructive pulmonary disease, and silicosis. There is currently no effective clinical drug treatment. It has been reported that grape seed extracts (GSE) has extensive pharmacological effects with minimal toxicity. Although it has been found that GSE can improve the lung collagen deposition and fibrosis pathology induced by bleomycin in rat, its effects on pulmonary function, inflammation, growth factors, matrix metalloproteinases and epithelial-mesenchymal transition remain to be researched. In the present study, we studied whether GSE provided protection against bleomycin (BLM)-induced mouse pulmonary fibrosis. ICR strain mice were treated with BLM in order to establish pulmonary fibrosis models. GSE was given daily via intragastric administration for three weeks starting at one day after intratracheal instillation. GSE at 50 or 100mg/kg significantly reduced BLM-induced inflammatory cells infiltration, proinflammatory factor protein expression, and hydroxyproline in lung tissues, and improved pulmonary function in mice. Additionally, treatment with GSE also significantly impaired BLM-induced increases in lung fibrotic marker expression (collagen type I alpha 1 and fibronectin 1) and decreases in an anti-fibrotic marker (E-cadherin). Further investigation indicated that the possible molecular targets of GSE are matrix metalloproteinases-9 (MMP-9) and TGF-β1, given that treatment with GSE significantly prevented BLM-induced increases in MMP-9 and TGF-β1 expression in the lungs. Together, these results suggest that supplementation with GSE may improve the quality of life of lung fibrosis patients by inhibiting MMP-9 and TGF-β1 expression in the lungs. Copyright © 2017 Elsevier B.V. All rights reserved.

Assessment of pulmonary structure-function relationships in young children and adolescents with cystic fibrosis by multivolume proton-MRI and CT.

PubMed

Pennati, Francesca; Roach, David J; Clancy, John P; Brody, Alan S; Fleck, Robert J; Aliverti, Andrea; Woods, Jason C

2018-02-19

Lung disease is the most frequent cause of morbidity and mortality in patients with cystic fibrosis (CF), and there is a shortage of sensitive biomarkers able to regionally monitor disease progression and to assess early responses to therapy. To determine the feasibility of noncontrast-enhanced multivolume MRI, which assesses intensity changes between expiratory and inspiratory breath-hold images, to detect and quantify regional ventilation abnormalities in CF lung disease, with a focus on the structure-function relationship. Retrospective. Twenty-nine subjects, including healthy young children (n = 9, 7-37 months), healthy adolescents (n = 4, 14-22 years), young children with CF lung disease (n = 10, 7-47 months), and adolescents with CF lung disease (n = 6, 8-18 years) were studied. 3D spoiled gradient-recalled sequence at 1.5T. Subjects were scanned during breath-hold at functional residual capacity (FRC) and total lung capacity (TLC) through noncontrast-enhanced MRI and CT. Expiratory-inspiratory differences in MR signal-intensity (Δ 1 H-MRI) and CT-density (ΔHU) were computed to estimate regional ventilation. MR and CT images were also evaluated using a CF-specific scoring system. Quadratic regression, Spearman's correlation, one-way analysis of variance (ANOVA). Δ 1 H-MRI maps were sensitive to ventilation heterogeneity related to gravity dependence in healthy lung and to ventilation impairment in CF lung disease. A high correlation was found between MRI and CT ventilation maps (R 2  = 0.79, P < 0.001). Globally, Δ 1 H-MRI and ΔHU decrease with increasing morphological score (respectively, R 2  = 0.56, P < 0.001 and R 2  = 0.31, P < 0.001). Locally, Δ 1 H-MRI was higher in healthy regions (median 15%) compared to regions with bronchiectasis, air trapping, consolidation, and to segments fed by airways with bronchial wall thickening (P < 0.001). Multivolume noncontrast-enhanced MRI, as a nonionizing imaging modality that can be used on nearly any MRI scanner without specialized equipment or gaseous tracers, may be particularly valuable in CF care, providing a new imaging biomarker to detect early alterations in regional lung structure-function. 3 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018. © 2018 International Society for Magnetic Resonance in Medicine.

Correlation between pulmonary function and brain volume in healthy elderly subjects.

PubMed

Taki, Yasuyuki; Kinomura, Shigeo; Ebihara, Satoru; Thyreau, Benjamin; Sato, Kazunori; Goto, Ryoi; Kakizaki, Masako; Tsuji, Ichiro; Kawashima, Ryuta; Fukuda, Hiroshi

2013-06-01

Cigarette smoking decreases brain regional gray matter volume and is related to chronic obstructive lung disease (COPD). COPD leads to decreased pulmonary function, which is represented by forced expiratory volume in one second percentage (FEV1.0 %); however, it is unclear if decreased pulmonary function is directly related to brain gray matter volume decline. Because there is a link between COPD and cognitive decline, revealing a direct relationship between pulmonary function and brain structure is important to better understand how pulmonary function affects brain structure and cognitive function. Therefore, the purpose of this study was to analyze whether there were significant correlations between FEV1.0 % and brain regional gray and white matter volumes using brain magnetic resonance (MR) image data from 109 community-dwelling healthy elderly individuals. Brain MR images were processed with voxel-based morphometry using a custom template by applying diffeomorphic anatomical registration using the exponentiated lie algebra procedure. We found a significant positive correlation between the regional white matter volume of the cerebellum and FEV1.0 % after adjusting for age, sex, and intracranial volume. Our results suggest that elderly individuals who have a lower FEV1.0 % have decreased regional white matter volume in the cerebellum. Therefore, preventing decreased pulmonary function is important for cerebellar white matter volume in the healthy elderly population.

Long-acting muscarinic antagonist use in adults with asthma: real-life prescribing and outcomes of add-on therapy with tiotropium bromide.

PubMed

Price, David; Kaplan, Alan; Jones, Rupert; Freeman, Daryl; Burden, Anne; Gould, Shuna; von Ziegenweidt, Julie; Ali, Muzammil; King, Christine; Thomas, Mike

2015-01-01

Randomized controlled trials indicate that addition of a long-acting muscarinic antagonist (LAMA) such as tiotropium may improve asthma control and reduce exacerbation risk in patients with poorly controlled asthma, but broader clinical studies are needed to investigate the effectiveness of LAMA in real-life asthma care. Medical records of adults with asthma (aged ≥18 years) prescribed tiotropium were obtained from the UK Optimum Patient Care Research Database for the period 2001-2013. Patients diagnosed with chronic obstructive pulmonary disease were excluded, but no other clinical exclusions were applied. Two primary outcomes were compared in the year before (baseline) and the year after (outcome) addition of tiotropium: exacerbations (asthma-related hospital emergency department attendance or inpatient admission, or acute oral corticosteroid course) and acute respiratory events (exacerbation or antibiotic prescription with lower respiratory consultation). Secondary outcomes included lung function test results and short-acting β2 agonist usage. The Wilcoxon signed-rank test was used for variables measured on the interval scale, the marginal homogeneity test for categorized variables, and the paired t-test for lung function indices. Of the 2,042 study patients, 83% were prescribed an inhaled corticosteroid and 68% a long-acting β2 agonist during the baseline year; 67% were prescribed both. Comparing baseline and outcome years, the percentage of patients having at least one exacerbation decreased from 37% to 27% (P<0.001) and the percentage having at least one acute respiratory event decreased from 58% to 47% (P<0.001). There were no significant changes in lung function, and usage of short-acting β2 agonists (in salbutamol/albuterol equivalents) increased from a median (interquartile range) of 274 (110, 548) to 329 (110, 603) μg/day (P=0.01). In this real-life asthma population, addition of LAMA therapy was associated with significant decreases in the incidence of exacerbations and antibiotic prescriptions for lower respiratory tract infections in the following year.

Prevalence of abnormal findings when adopting new national and international Global Lung Function Initiative reference values for spirometry in the Finnish general population

PubMed Central

Kainu, Annette; Lindqvist, Ari; Sovijärvi, Anssi R. A.

2016-01-01

Background New Finnish (Kainu2015) and international Global Lung Function Initiative (GLI2012) reference values for spirometry were recently published. The aim of this study is to compare the interpretative consequences of adopting these new reference values with older, currently used Finnish reference values (Viljanen1982) in the general population of native Finns. Methods Two Finnish general population samples including 1,328 adults (45% males) aged 21–74 years were evaluated. Airway obstruction was defined as a reduced ratio of forced expiratory volume in one second (FEV1)/forced vital capacity (FVC), possible restrictive pattern as reduced FVC, and decreased ventilatory capacity as reduced FEV1 below their respective 2.5th percentiles. The severity gradings of reduced lung function were also compared. Results Using the Kainu2015 reference values, the prevalence of airway obstruction in the population was 5.6%; using GLI2012 it was 4.0% and with Viljanen1982 it was 13.0%. Possible restrictive pattern was found in 4.2% using the Kainu2015 values, in 2.0% with GLI2012, and 7.9% with the Viljanen1982 values. The prevalence of decreased ventilatory capacity was 6.8, 4.0, and 13.3% with the Kainu2015, GLI2012 and Viljanen1982 values, respectively. Conclusions The application of the GLI2012 reference values underestimates the prevalence of abnormal spirometric findings in native Finns. The adoption of the Kainu2015 reference values reduces the prevalences of airways obstruction, decreased ventilatory capacity, and restrictive impairment by approximately 50%. Changing from the 2.5th percentile, the previously used lower limit of normal, to the 5th percentile recommended by the American Thoracic Society/European Respiratory Society will not increase the prevalence of abnormal findings in the implementation of spirometry reference values. PMID:27608270

Dose-response relationships between occupational exposure to potash, diesel exhaust and nitrogen oxides and lung function: cross-sectional and longitudinal study in two salt mines.

PubMed

Lotz, Gabriele; Plitzko, Sabine; Gierke, Erhardt; Tittelbach, Ulrike; Kersten, Norbert; Schneider, W Dietmar

2008-08-01

Several studies have shown that underground salt miners may have an increased incidence of chest symptoms and sometimes decreased lung function. Miners of two salt mines were investigated to evaluate relationships between the lung function and the workplace exposure. The effect of nitrogen monoxide (NO) and nitrogen dioxide (NO(2)) was investigated in view of the recent debate on European occupational exposure limits. A total of 410/463 miners (mine A/mine B) were examined cross-sectional and 75/64% of the first cohort were examined after a 5-year period. Exposure was measured by personal sampling. Personal lifetime exposure doses of salt dust, diesel exhaust, NO(2) and NO were calculated for all miners. Dose-response relationships were calculated by multiple regression analysis. Each exposure component acted as an indicator for the complex exposure. Exposure response relationships were shown in the cross-sectional and longitudinal investigations in both mines. In the 5-year period, the adjusted (age, smoking, etc.) effect of the exposure indicators resulted in a mean decrease of FEV(1) between -18 ml/year (mine A) and -10 ml/year (mine B). The personal concentrations related to this effect were 12.6/7.1 mg/m(3) inhalable dust, 2.4/0.8 mg/m(3) respirable dust, 0.09/0.09 mg/m(3) diesel exhaust, 0.4/0.5 ppm NO(2) and 1.7/1.4 ppm NO (mine A/B). Exposure was related to symptoms of chronic bronchitis only in mine B. The effects found in both mines indicate that the mixed exposure can cause lung function disorders in salt miners exposed over a long time. Because of the high correlation of the concentrations it was not possible to determine the effects of a single exposure component separately or to recommend a specific occupational exposure limit. However, possible maximum effects associated with the mixed exposure can be evaluated in the ranges of concentrations of the individual substances in the mines.

Crackle Pitch Rises Progressively during Inspiration in Pneumonia, CHF, and IPF Patients.

PubMed

Vyshedskiy, Andrey; Murphy, Raymond

2012-01-01

Objective. It is generally accepted that crackles are due to sudden opening of airways and that larger airways produce crackles of lower pitch than smaller airways do. As larger airways are likely to open earlier in inspiration than smaller airways and the reverse is likely to be true in expiration, we studied crackle pitch as a function of crackle timing in inspiration and expiration. Our goal was to see if the measurement of crackle pitch was consistent with this theory. Methods. Patients with a significant number of crackles were examined using a multichannel lung sound analyzer. These patients included 34 with pneumonia, 38 with heart failure, and 28 with interstitial fibrosis. Results. Crackle pitch progressively increased during inspirations in 79% of all patients. In these patients crackle pitch increased by approximately 40 Hz from the early to midinspiration and by another 40 Hz from mid to late-inspiration. In 10% of patients, crackle pitch did not change and in 11% of patients crackle pitch decreased. During expiration crackle pitch progressively decreased in 72% of patients and did not change in 28% of patients. Conclusion. In the majority of patients, we observed progressive crackle pitch increase during inspiration and decrease during expiration. Increased crackle pitch at larger lung volumes is likely a result of recruitment of smaller diameter airways. An alternate explanation is that crackle pitch may be influenced by airway tension that increases at greater lung volume. In any case improved understanding of the mechanism of production of these common lung sounds may help improve our understanding of pathophysiology of these disorders.

Effect of CPAP in a Mouse Model of Hyperoxic Neonatal Lung Injury

PubMed Central

Reyburn, Brent; Fiore, Juliann M. Di; Raffay, Thomas; Martin, Richard J.; Y.S., Prakash; Jafri, Anjum; MacFarlane, Peter M.

2015-01-01

Background Continuous positive airway pressure [CPAP] and supplemental oxygen have become the mainstay of neonatal respiratory support in preterm infants. Although oxygen therapy is associated with respiratory morbidities including bronchopulmonary dysplasia [BPD], the long-term effects of CPAP on lung function are largely unknown. We used a hyperoxia-induced mouse model of BPD to explore the effects of daily CPAP during the first week of life on later respiratory system mechanics. Objective To test the hypothesis that daily CPAP in a newborn mouse model of BPD improves longer term respiratory mechanics. Methods Mouse pups from C57BL/6 pregnant dams were exposed to room air [RA] or hyperoxia [50% O2, 24hrs/day] for the first postnatal week with or without exposure to daily CPAP [6cmH2O, 3hrs/day]. Respiratory system resistance [Rrs] and compliance [Crs] were measured following a subsequent 2 week period of room RA recovery. Additional measurements included radial alveolar counts and macrophage counts. Results Mice exposed to hyperoxia had significantly elevated Rrs, decreased Crs, reduced alveolarization, and increased macrophage counts at three weeks compared to RA treated mice. Daily CPAP treatment significantly improved Rrs, Crs and alveolarization, and decreased lung macrophage infiltration in hyperoxia-exposed pups. Conclusions We have demonstrated that daily CPAP had a longer term benefit on baseline respiratory system mechanics in a neonatal mouse model of BPD. We speculate that this beneficial effect of CPAP was the consequence of a decrease in the inflammatory response and resultant alveolar injury associated with hyperoxic newborn lung injury. PMID:26394387

Impact of the CFTR-potentiator ivacaftor on airway microbiota in cystic fibrosis patients carrying a G551D mutation.

PubMed

Bernarde, Cédric; Keravec, Marlène; Mounier, Jérôme; Gouriou, Stéphanie; Rault, Gilles; Férec, Claude; Barbier, Georges; Héry-Arnaud, Geneviève

2015-01-01

Airway microbiota composition has been clearly correlated with many pulmonary diseases, and notably with cystic fibrosis (CF), an autosomal genetic disorder caused by mutation in the CF transmembrane conductance regulator (CFTR). Recently, a new molecule, ivacaftor, has been shown to re-establish the functionality of the G551D-mutated CFTR, allowing significant improvement in lung function. The purpose of this study was to follow the evolution of the airway microbiota in CF patients treated with ivacaftor, using quantitative PCR and pyrosequencing of 16S rRNA amplicons, in order to identify quantitative and qualitative changes in bacterial communities. Three G551D children were followed up longitudinally over a mean period of more than one year covering several months before and after initiation of ivacaftor treatment. 129 operational taxonomy units (OTUs), representing 64 genera, were identified. There was no significant difference in total bacterial load before and after treatment. Comparison of global community composition found no significant changes in microbiota. Two OTUs, however, showed contrasting dynamics: after initiation of ivacaftor, the relative abundance of the anaerobe Porphyromonas 1 increased (p<0.01) and that of Streptococcus 1 (S. mitis group) decreased (p<0.05), possibly in relation to the anti-Gram-positive properties of ivacaftor. The anaerobe Prevotella 2 correlated positively with the pulmonary function test FEV-1 (r=0.73, p<0.05). The study confirmed the presumed positive role of anaerobes in lung function. Several airway microbiota components, notably anaerobes (obligate or facultative anaerobes), could be valuable biomarkers of lung function improvement under ivacaftor, and could shed light on the pathophysiology of lung disease in CF patients.

Radionuclide injury to the lung.

PubMed Central

Dagle, G E; Sanders, C L

1984-01-01

Radionuclide injury to the lung has been studied in rats, hamsters, dogs, mice and baboons. Exposure of the lung to high dose levels of radionuclides produces a spectrum of progressively more severe functional and morphological changes, ranging from radiation pneumonitis and fibrosis to lung tumors. These changes are somewhat similar for different species. Their severity can be related to the absorbed radiation dose (measured in rads) produced by alpha, beta or gamma radiation emanating from various deposited radionuclides. The chemicophysical forms of radionuclides and spatial-temporal factors are also important variables. As with other forms of injury to the lung, repair attempts are highlighted by fibrosis and proliferation of pulmonary epithelium. Lung tumors are the principal late effect observed in experimental animals following pulmonary deposition of radionuclides at dose levels that do not result in early deaths from radiation pneumonitis or fibrosis. The predominant lung tumors described have been of epithelial origin and have been classified, in decreasing frequency of occurrence, as adenocarcinoma, bronchioloalveolar carcinoma, epidermoid carcinomas and combined epidermoid and adenocarcinoma. Mesothelioma and fibrosarcoma have been observed in rats, but less commonly in other species. Hemangiosarcomas were frequency observed in dogs exposed to beta-gamma emitters, and occasionally in rats exposed to alpha emitters. These morphologic changes in the lungs of experimental animals were reviewed and issues relevant to the prediction of human hazards discussed. PMID:6376095

The Transient Receptor Potential Vanilloid 1 Antagonist Capsazepine Improves the Impaired Lung Mechanics during Endotoxemia.

PubMed

Cabral, Layla D M; Giusti-Paiva, Alexandre

2016-11-01

Acute lung injury (ALI) caused by systemic inflammatory response remains a leading cause of morbidity and mortality in critically ill patients. Management of patients with sepsis is largely limited to supportive therapies, reflecting an incomplete understanding of the underlying pathophysiology. Furthermore, there have been limited advances in the treatments for ALI. In this study, lung function and a histological analysis were performed to evaluate the impact of transient receptor potential vanilloid-1 receptor (TRPV1) antagonist (capsazepine; CPZ) on the lipopolysaccharide (LPS)-induced lung injury in mice. For this, adult mice pre-treated with CPZ or vehicle received intraperitoneal injections of LPS or saline and 24 hr after, the mice were anaesthetized, and lung mechanics was evaluated. The LPS-challenged mice exhibited substantial mechanical impairment, characterized by increases in respiratory system resistance, respiratory system elastance, tissue damping and tissue elastance. The pre-treatment with CPZ prevented the increase in respiratory system resistance and decreased the increase in tissue damping during endotoxemia. In addition, mice pre-treated with CPZ had an attenuated lung injury evidenced by reduction on collapsed area of the lung parenchyma induced by LPS. This suggests that the TRPV1 antagonist capsazepine has a protective effect on lung mechanics in ALI during endotoxemia and that it may be a target for enhanced therapeutic efficacy in ALI. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Bioenergetics of lung tumors: alteration of mitochondrial biogenesis and respiratory capacity.

PubMed

Bellance, N; Benard, G; Furt, F; Begueret, H; Smolková, K; Passerieux, E; Delage, J P; Baste, J M; Moreau, P; Rossignol, R

2009-12-01

Little is known on the metabolic profile of lung tumors and the reminiscence of embryonic features. Herein, we determined the bioenergetic profiles of human fibroblasts taken from lung epidermoid carcinoma (HLF-a) and fetal lung (MRC5). We also analysed human lung tumors and their surrounding healthy tissue from four patients with adenocarcinoma. On these different models, we measured functional parameters (cell growth rates in oxidative and glycolytic media, respiration, ATP synthesis and PDH activity) as well as compositional features (expression level of various energy proteins and upstream transcription factors). The results demonstrate that both the lung fetal and cancer cell lines produced their ATP predominantly by glycolysis, while oxidative phosphorylation was only capable of poor ATP delivery. This was explained by a decreased mitochondrial biogenesis caused by a lowered expression of PGC1alpha (as shown by RT-PCR and Western blot) and mtTFA. Consequently, the relative expression of glycolytic versus OXPHOS markers was high in these cells. Moreover, the re-activation of mitochondrial biogenesis with resveratrol induced cell death specifically in cancer cells. A consistent reduction of mitochondrial biogenesis and the subsequent alteration of respiratory capacity was also observed in lung tumors, associated with a lower expression level of bcl2. Our data give a better characterization of lung cancer cells' metabolic alterations which are essential for growth and survival. They designate mitochondrial biogenesis as a possible target for anti-cancer therapy.

Effect of radon on the immune system: alterations in the cellularity and functions of T cells in lymphoid organs of mouse.

PubMed

Nagarkatti, M; Nagarkatti, P S; Brooks, A

1996-04-19

Exposure to radon and its progeny induces significant damage to the cells of the respiratory tract and causes lung cancer. Whether a similar exposure to radon would alter the functions of the immune system has not been previously investigated. In the current study, we investigated the effect of exposure of C57BL/6 mice to 1000 or 2500 working-level months (WLM) of radon and its progeny by inhalation, on the number and function of T lymphocytes in lymphoid organs. The control mice received uranium ore dust carrier aerosol by inhalation. Exposure to radon induced marked decrease in the total cellularity of most lymphoid organs such as thymus, peripheral lymph nodes (PLN), and lung-associated lymph nodes (LALN), when compared to the controls. The percentage of T cells increased, while that of non-T cells decreased, in all peripheral lymphoid organs at both the doses of radon. In the thymus, particularly at 2500 WLM of radon exposure, there was a marked decrease in CD4+CD8+ T cells and an increase in the immature CD4-CD8- T cells. Such alterations in both the numbers and percentages of lymphocytes and macrophages in radon-exposed mice may have resulted from the cell killing by the alpha particles as the immune cells were migrating through the lungs, or it may have been caused by altered migration of cells, inasmuch as expression of CD44, a molecule involved in migration and homing of immune cells, was significantly altered on cells found in different lymphoid organs. In the LALN, where one would predict the largest number of damaged cells to be present, there was a significant decrease in the T-cell responsiveness to mitogens while the B-cell response was not affected. Such alterations may have resulted from the direct effect of alpha-particle exposure on the migrating lymphocytes, altered percentage of lymphocytes as seen in secondary lymphoid organs, or altered expression of adhesion molecules involved in cell activation such as CD44 and CD3. Interestingly, radon exposure caused and increase in the T- and B-cell responsiveness to mitogens in the spleen and PLN. Since there is little evidence of direct radiation dose from radon in lymphoid organs, our studies demonstrating immunological alterations suggest an indirect effect of radon exposure that may have significant repercussions on the development of hypersensitivity and increased susceptibility to infections and cancer in the lung.

Chest physiotherapy can affect the lung clearance index in cystic fibrosis patients.

PubMed

Grosse-Onnebrink, Joerg; Mellies, Uwe; Olivier, Margarete; Werner, Claudius; Stehling, Florian

2017-05-01

The lung clearance index (LCI) is determined by multiple-breath washout lung function (MBW). It is increasingly used as an endpoint in clinical trials. Chest physiotherapy (CP) is part of routine cystic fibrosis (CF) care. Whether the LCI is useful in detecting short-term treatment effects of CP has not been sufficiently investigated. We assessed the short-term influence of CP with highly standardized high-frequency chest wall oscillation (HFCWO) on the LCI in CF patients. In this randomized controlled study, the LCI was obtained in 20 CF patients (7-34 years) hospitalized for infective pulmonary exacerbation prior to and immediately after a single treatment of HFCWO. Twenty-one control group CF patients (7-51 years) received no treatment. We calculated the coefficient of repeatability (CR) to estimate the clinical relevance of possible treatment effects. HFCWO improved (ie, decreased) the LCI by a median of 0.9 (range -0.45; 3.47; P = 0.002); the LCI decreased in 15 of 20 intervention group patients. In five patients the decrease in LCI exceeded the CR (2.15), indicating a clinically relevant treatment effect; in five patients the LCI increased but did not exceed the CR. The LCI did not change significantly in the control group patients. HFCWO can have a short-term decreasing effect on the LCI, but the treatment response is heterogeneous. In future trials using LCI as an endpoint, the timing of CP in relation to MBW should be considered a possible bias. © 2017 Wiley Periodicals, Inc.

Magnetic resonance assessment of parenchymal elasticity in normal and edematous, ventilator-injured lung.

PubMed

McGee, Kiaran P; Mariappan, Yogesh K; Hubmayr, Rolf D; Carter, Rickey E; Bao, Zhonghao; Levin, David L; Manduca, Armando; Ehman, Richard L

2012-08-15

Magnetic resonance elastography (MRE) is a MR imaging method capable of spatially resolving the intrinsic mechanical properties of normal lung parenchyma. We tested the hypothesis that the mechanical properties of edematous lung exhibit local properties similar to those of a fluid-filled lung at transpulmonary pressures (P(tp)) up to 25 cm H(2)O. Pulmonary edema was induced in anesthetized female adult Sprague-Dawley rats by mechanical ventilation to a pressure of 40 cm H(2)O for ≈ 30 min. Prior to imaging the wet weight of each ex vivo lung set was measured. MRE, high-resolution T(1)-weighted spin echo and T(2)* gradient echo data were acquired at each P(tp) for both normal and injured ex vivo lungs. At P(tp)s of 6 cm H(2)O and greater, the shear stiffness of normal lungs was greater than injured lungs (P ≤ 0.0003). For P(tp)s up to 12 cm H(2)O, shear stiffness was equal to 1.00, 1.07, 1.16, and 1.26 kPa for the injured and 1.31, 1.89, 2.41, and 2.93 kPa for normal lungs at 3, 6, 9, and 12 cm H(2)O, respectively. For injured lungs MRE magnitude signal and shear stiffness within regions of differing degrees of alveolar flooding were calculated as a function of P(tp). Differences in shear stiffness were statistically significant between groups (P < 0.001) with regions of lower magnitude signal being stiffer than those of higher signal. These data demonstrate that when the alveolar space filling material is fluid, MRE-derived parenchymal shear stiffness of the lung decreases, and the lung becomes inherently softer compared with normal lung.

Stem cell conditioned medium improves acute lung injury in mice: in vivo evidence for stem cell paracrine action.

PubMed

Ionescu, Lavinia; Byrne, Roisin N; van Haaften, Tim; Vadivel, Arul; Alphonse, Rajesh S; Rey-Parra, Gloria J; Weissmann, Gaia; Hall, Adam; Eaton, Farah; Thébaud, Bernard

2012-12-01

Mortality and morbidity of acute lung injury and acute respiratory distress syndrome remain high because of the lack of pharmacological therapies to prevent injury or promote repair. Mesenchymal stem cells (MSCs) prevent lung injury in various experimental models, despite a low proportion of donor-derived cell engraftment, suggesting that MSCs exert their beneficial effects via paracrine mechanisms. We hypothesized that soluble factors secreted by MSCs promote the resolution of lung injury in part by modulating alveolar macrophage (AM) function. We tested the therapeutic effect of MSC-derived conditioned medium (CdM) compared with whole MSCs, lung fibroblasts, and fibroblast-CdM. Intratracheal MSCs and MSC-CdM significantly attenuated lipopolysaccharide (LPS)-induced lung neutrophil influx, lung edema, and lung injury as assessed by an established lung injury score. MSC-CdM increased arginase-1 activity and Ym1 expression in LPS-exposed AMs. In vivo, AMs from LPS-MSC and LPS-MSC CdM lungs had enhanced expression of Ym1 and decreased expression of inducible nitric oxide synthase compared with untreated LPS mice. This suggests that MSC-CdM promotes alternative macrophage activation to an M2 "healer" phenotype. Comparative multiplex analysis of MSC- and fibroblast-CdM demonstrated that MSC-CdM contained several factors that may confer therapeutic benefit, including insulin-like growth factor I (IGF-I). Recombinant IGF-I partially reproduced the lung protective effect of MSC-CdM. In summary, MSCs act through a paracrine activity. MSC-CdM promotes the resolution of LPS-induced lung injury by attenuating lung inflammation and promoting a wound healing/anti-inflammatory M2 macrophage phenotype in part via IGF-I.

Stem cell conditioned medium improves acute lung injury in mice: in vivo evidence for stem cell paracrine action

PubMed Central

Ionescu, Lavinia; Byrne, Roisin N.; van Haaften, Tim; Vadivel, Arul; Alphonse, Rajesh S.; Rey-Parra, Gloria J.; Weissmann, Gaia; Hall, Adam; Eaton, Farah

2012-01-01

Mortality and morbidity of acute lung injury and acute respiratory distress syndrome remain high because of the lack of pharmacological therapies to prevent injury or promote repair. Mesenchymal stem cells (MSCs) prevent lung injury in various experimental models, despite a low proportion of donor-derived cell engraftment, suggesting that MSCs exert their beneficial effects via paracrine mechanisms. We hypothesized that soluble factors secreted by MSCs promote the resolution of lung injury in part by modulating alveolar macrophage (AM) function. We tested the therapeutic effect of MSC-derived conditioned medium (CdM) compared with whole MSCs, lung fibroblasts, and fibroblast-CdM. Intratracheal MSCs and MSC-CdM significantly attenuated lipopolysaccharide (LPS)-induced lung neutrophil influx, lung edema, and lung injury as assessed by an established lung injury score. MSC-CdM increased arginase-1 activity and Ym1 expression in LPS-exposed AMs. In vivo, AMs from LPS-MSC and LPS-MSC CdM lungs had enhanced expression of Ym1 and decreased expression of inducible nitric oxide synthase compared with untreated LPS mice. This suggests that MSC-CdM promotes alternative macrophage activation to an M2 “healer” phenotype. Comparative multiplex analysis of MSC- and fibroblast-CdM demonstrated that MSC-CdM contained several factors that may confer therapeutic benefit, including insulin-like growth factor I (IGF-I). Recombinant IGF-I partially reproduced the lung protective effect of MSC-CdM. In summary, MSCs act through a paracrine activity. MSC-CdM promotes the resolution of LPS-induced lung injury by attenuating lung inflammation and promoting a wound healing/anti-inflammatory M2 macrophage phenotype in part via IGF-I. PMID:23023971

Expression of T-box transcription factors 2, 4 and 5 is decreased in the branching airway mesenchyme of nitrofen-induced hypoplastic lungs.

PubMed

Takahashi, Toshiaki; Friedmacher, Florian; Zimmer, Julia; Puri, Prem

2017-02-01

Pulmonary hypoplasia (PH), characterized by smaller lung size and reduced airway branching, remains a major therapeutic challenge in newborns with congenital diaphragmatic hernia (CDH). T-box transcription factors (Tbx) have been identified as key components of the gene network that regulates fetal lung development. Tbx2, Tbx4 and Tbx5 are expressed throughout the mesenchyme of the developing lung, regulating the process of lung branching morphogenesis. Furthermore, lungs of Tbx2-, Tbx4- and Tbx5-deficient mice are hypoplastic and exhibit decreased lung branching, similar to PH in human CDH. We hypothesized that the expression of Tbx2, Tbx4 and Tbx5 is decreased in the branching airway mesenchyme of hypoplastic rat lungs with nitrofen-induced CDH. Time-mated rats received either nitrofen or vehicle on gestational day 9 (D9). Fetuses were killed on D15, D18 and D21, and dissected lungs were divided into control and nitrofen-exposed specimens. Pulmonary gene expression of Tbx2, Tbx4 and Tbx5 was investigated by quantitative real-time polymerase chain reaction. Immunofluorescence double staining for Tbx2, Tbx4 and Tbx5 was combined with the mesenchymal marker Fgf10 to assess protein expression and localization in branching airway tissue. Relative mRNA levels of Tbx2, Tbx4 and Tbx5 were significantly reduced in lungs of nitrofen-exposed fetuses on D15, D18 and D21 compared to controls. Confocal laser scanning microscopy showed markedly diminished immunofluorescence of Tbx2, Tbx4 and Tbx5 in mesenchymal cells surrounding branching airways of nitrofen-exposed fetuses on D15, D18 and D21 compared to controls. Decreased expression of Tbx2, Tbx4 and Tbx5 in the pulmonary mesenchyme during fetal lung development may lead to a decrease or arrest of airway branching, thus contributing to PH in the nitrofen-induced CDH model.

[Effects of sodium aescinate on the apoptosis-related genes in lung injury induced by intestinal ischemia reperfusion in rats].

PubMed

Wang, Yan-Lei; Jing, You-Ling; Cai, Qing-Yan; Cui, Guo-Jin; Zhang, Yi-Bing; Zhang, Feng-Yu

2012-03-01

To investigate the relationship between apoptosis-related genes and lung injury induced by intestinal ischemia reperfusion and to explore the effects and its possible mechanism of sodium aescinate. Rat model of intestinal I/R injury was established with clamping of the superior mesenteric artery for 60 min and then clamping was relieved for 60 min. Twenty-four SD rats were randomly divided into three groups with eight rats in each: sham group, intestinal ischemia/reperfusion group (I/R group) and sodium aescinate group (SA + I/R group). Lung wet/dry weight ratio, lung coefficient and Superoxide dismutase (SOD), malondialdehyde (MDA) in plasma and lung tissue were measured, as well as the expression levels of Bcl-2 and Bax proteins in lung tissue were examined using immunohistochemical method. Compared with sham group, lung wet/dry weight ratio, lung coefficient and MDA in plasma and lung tissue were significantly increased, and while the activity of SOD in plasma and lung tissue were decreased significantly in I/R group. At the same time, the protein expression level of Bcl-2 and Bax were significantly increased. But Bax protein expression was much greater than that of Bcl-2, the ratio of Bcl-2 to Bax was decreased significantly in I/R group than that in sham group. Compared with I/R group, lung wet/dry weight ratio, lung coefficient and MDA in plasma and lung tissue were significantly decreased, and while the activity of SOD in serum and lung tissue were significantly increased in SA + I/R group. At the same time, Bax protein expression was significantly decreased, both Bcl-2 protein expression and the ratio of Bcl-2 to Bax were significantly increased in SA + I/R group than that in I/R group. Lung injury induced by intestinal ischemia reperfusion is correlated with abnormal expression levels of Bcl-2 and Bax protein which is caused by oxidative injury. Sodium aescinate can protect the lung injury induced by intestinal ischemia/reperfusion (I/R), which may be mediated by inhibiting lipid peroxidation, upregulating Bcl-2 gene protein expression, improving the ratio of Bcl-2/ Bax to inhibit lung apoptosis.

Decreased endothelial nitric oxide synthase expression and function contribute to impaired mitochondrial biogenesis and oxidative stress in fetal lambs with persistent pulmonary hypertension.

PubMed

Afolayan, Adeleye J; Eis, Annie; Alexander, Maxwell; Michalkiewicz, Teresa; Teng, Ru-Jeng; Lakshminrusimha, Satyan; Konduri, Girija G

2016-01-01

Impaired vasodilation in persistent pulmonary hypertension of the newborn (PPHN) is characterized by mitochondrial dysfunction. We investigated the hypothesis that a decreased endothelial nitric oxide synthase level leads to impaired mitochondrial biogenesis and function in a lamb model of PPHN induced by prenatal ductus arteriosus constriction. We ventilated PPHN lambs with 100% O2 alone or with inhaled nitric oxide (iNO). We treated pulmonary artery endothelial cells (PAECs) from normal and PPHN lambs with detaNONOate, an NO donor. We observed decreased mitochondrial (mt) DNA copy number, electron transport chain (ETC) complex subunit levels, and ATP levels in PAECs and lung tissue of PPHN fetal lambs at baseline compared with gestation matched controls. Phosphorylation of AMP-activated kinase (AMPK) and levels of peroxisome proliferator-activated receptor-γ coactivator 1-α (PGC-1α) and sirtuin-1, which facilitate mitochondrial biogenesis, were decreased in PPHN. Ventilation with 100% O2 was associated with larger decreases in ETC subunits in the lungs of PPHN lambs compared with unventilated PPHN lambs. iNO administration, which facilitated weaning of FiO2 , partly restored mtDNA copy number, ETC subunit levels, and ATP levels. DetaNONOate increased eNOS phosphorylation and its interaction with heat shock protein 90 (HSP90); increased levels of superoxide dismutase 2 (SOD2) mRNA, protein, and activity; and decreased the mitochondrial superoxide levels in PPHN-PAECs. Knockdown of eNOS decreased ETC protein levels in control PAECs. We conclude that ventilation with 100% O2 amplifies oxidative stress and mitochondrial dysfunction in PPHN, which are partly improved by iNO and weaning of oxygen. Copyright © 2016 the American Physiological Society.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ar Latin-Small-Letter-Dotless-I bas, Bilgin Kadri, E-mail: bilginaribas@hotmail.com; Dingil, Guerbuez; Koeroglu, Mert

The aim of this case study is to present effectiveness of percutaneous drainage as a treatment option of ruptured lung and liver hydatid cysts. A 65-year-old male patient was admitted with complicated liver and lung hydatid cysts. A liver hydatid cyst had ruptured transdiaphragmatically, and a lung hydatid cyst had ruptured both into bronchi and pleural space. The patient could not undergo surgery because of decreased respiratory function. Both cysts were drained percutaneously using oral albendazole. Povidone-iodine was used to treat the liver cyst after closure of the diaphragmatic rupture. The drainage was considered successful, and the patient had nomore » recurrence of signs and symptoms. Clinical, laboratory, and radiologic recovery was observed during 2.5 months of catheterization. The patient was asymptomatic after catheter drainage. No recurrence was detected during 86 months of follow-up. For inoperable patients with ruptured liver and lung hydatid cysts, percutaneous drainage with oral albendazole is an alternative treatment option to surgery. The percutaneous approach can be life-saving in such cases.« less

Vascular Endothelial Cell-Specific Connective Tissue Growth Factor (CTGF) Is Necessary for Development of Chronic Hypoxia-Induced Pulmonary Hypertension.

PubMed

Pi, Liya; Fu, Chunhua; Lu, Yuanquing; Zhou, Junmei; Jorgensen, Marda; Shenoy, Vinayak; Lipson, Kenneth E; Scott, Edward W; Bryant, Andrew J

2018-01-01

Chronic hypoxia frequently complicates the care of patients with interstitial lung disease, contributing to the development of pulmonary hypertension (PH), and premature death. Connective tissue growth factor (CTGF), a matricellular protein of the Cyr61/CTGF/Nov (CCN) family, is known to exacerbate vascular remodeling within the lung. We have previously demonstrated that vascular endothelial-cell specific down-regulation of CTGF is associated with protection against the development of PH associated with hypoxia, though the mechanism for this effect is unknown. In this study, we generated a transgenic mouse line in which the Ctgf gene was floxed and deleted in vascular endothelial cells that expressed Cre recombinase under the control of VE-Cadherin promoter (eCTGF KO mice). Lack of vascular endothelial-derived CTGF protected against the development of PH secondary to chronic hypoxia, as well as in another model of bleomycin-induced pulmonary hypertension. Importantly, attenuation of PH was associated with a decrease in infiltrating inflammatory cells expressing CD11b or integrin α M (ITGAM), a known adhesion receptor for CTGF, in the lungs of hypoxia-exposed eCTGF KO mice. Moreover, these pathological changes were associated with activation of-Rho GTPase family member-cell division control protein 42 homolog (Cdc42) signaling, known to be associated with alteration in endothelial barrier function. These data indicate that endothelial-specific deletion of CTGF results in protection against development of chronic-hypoxia induced PH. This protection is conferred by both a decrease in inflammatory cell recruitment to the lung, and a reduction in lung Cdc42 activity. Based on our studies, CTGF inhibitor treatment should be investigated in patients with PH associated with chronic hypoxia secondary to chronic lung disease.

In Vivo Protective Effects of Nootkatone against Particles-Induced Lung Injury Caused by Diesel Exhaust Is Mediated via the NF-κB Pathway

PubMed Central

Nemmar, Abderrahim; Al-Salam, Suhail; Beegam, Sumaya; Yuvaraju, Priya; Hamadi, Naserddine; Ali, Badreldin H.

2018-01-01

Numerous studies have shown that acute particulate air pollution exposure is linked with pulmonary adverse effects, including alterations of pulmonary function, inflammation, and oxidative stress. Nootkatone, a constituent of grapefruit, has antioxidant and anti-inflammatory effects. However, the effect of nootkatone on lung toxicity has not been reported so far. In this study we evaluated the possible protective effects of nootkatone on diesel exhaust particles (DEP)-induced lung toxicity, and the possible mechanisms underlying these effects. Mice were intratracheally (i.t.) instilled with either DEP (30 µg/mouse) or saline (control). Nootkatone was given to mice by gavage, 1 h before i.t. instillation, with either DEP or saline. Twenty-four hours following DEP exposure, several physiological and biochemical endpoints were assessed. Nootkatone pretreatment significantly prevented the DEP-induced increase in airway resistance in vivo, decreased neutrophil infiltration in bronchoalveolar lavage fluid, and abated macrophage and neutrophil infiltration in the lung interstitium, assessed by histolopathology. Moreover, DEP caused a significant increase in lung concentrations of 8-isoprostane and tumor necrosis factor α, and decreased the reduced glutathione concentration and total nitric oxide activity. These actions were all significantly alleviated by nootkatone pretreatment. Similarly, nootkatone prevented DEP-induced DNA damage and prevented the proteolytic cleavage of caspase-3. Moreover, nootkatone inhibited nuclear factor-kappaB (NF-κB) induced by DEP. We conclude that nootkatone prevented the DEP-induced increase in airway resistance, lung inflammation, oxidative stress, and the subsequent DNA damage and apoptosis through a mechanism involving inhibition of NF-κB activation. Nootkatone could possibly be considered a beneficial protective agent against air pollution-induced respiratory adverse effects. PMID:29495362

Comparison of four software packages for CT lung volumetry in healthy individuals.

PubMed

Nemec, Stefan F; Molinari, Francesco; Dufresne, Valerie; Gosset, Natacha; Silva, Mario; Bankier, Alexander A

2015-06-01

To compare CT lung volumetry (CTLV) measurements provided by different software packages, and to provide normative data for lung densitometric measurements in healthy individuals. This retrospective study included 51 chest CTs of 17 volunteers (eight men and nine women; mean age, 30 ± 6 years), who underwent spirometrically monitored CT at total lung capacity (TLC), functional residual capacity (FRC), and mean inspiratory capacity (MIC). Volumetric differences assessed by four commercial software packages were compared with analysis of variance (ANOVA) for repeated measurements and benchmarked against the threshold for acceptable variability between spirometric measurements. Mean lung density (MLD) and parenchymal heterogeneity (MLD-SD) were also compared with ANOVA. Volumetric differences ranged from 12 to 213 ml (0.20 % to 6.45 %). Although 16/18 comparisons (among four software packages at TLC, MIC, and FRC) were statistically significant (P < 0.001 to P = 0.004), only 3/18 comparisons, one at MIC and two at FRC, exceeded the spirometry variability threshold. MLD and MLD-SD significantly increased with decreasing volumes, and were significantly larger in lower compared to upper lobes (P < 0.001). Lung volumetric differences provided by different software packages are small. These differences should not be interpreted based on statistical significance alone, but together with absolute volumetric differences. • Volumetric differences, assessed by different CTLV software, are small but statistically significant. • Volumetric differences are smaller at TLC than at MIC and FRC. • Volumetric differences rarely exceed spirometric repeatability thresholds at MIC and FRC. • Differences between CTLV measurements should be interpreted based on comparison of absolute differences. • MLD increases with decreasing volumes, and is larger in lower compared to upper lobes.

A prospective study of the impact of diabetes mellitus on restrictive and obstructive lung function impairment: The Saku study.

PubMed

Sonoda, Nao; Morimoto, Akiko; Tatsumi, Yukako; Asayama, Kei; Ohkubo, Takayoshi; Izawa, Satoshi; Ohno, Yuko

2018-05-01

To assess the impact of diabetes on restrictive and obstructive lung function impairment. This 5-year prospective study included 7524 participants aged 40-69years without lung function impairment at baseline who underwent a comprehensive medical check-up between April 2008 and March 2009 at Saku Central Hospital. Diabetes was defined by fasting plasma glucose ≥7.0mmol/l (126mg/dl), HbA1c≥6.5% (48mmol/mol), or a history of diabetes, as determined by interviews conducted by the physicians. Restrictive and obstructive lung function impairment were defined as forced vital capacity (FVC) <80% predicted and forced expiratory volume in 1s (FEV 1 ) to FVC ratio (FEV 1 /FVC) <0.70, respectively. Participants were screened until they developed restrictive or obstructive lung function impairment or until March 2014. During the follow-up period, 171 and 639 individuals developed restrictive and obstructive lung function impairment, respectively. Individuals with diabetes had a 1.6-fold higher risk of restrictive lung function impairment than those without diabetes after adjusting for sex, age, height, abdominal obesity, smoking status, exercise habits, systolic blood pressure, HDL-cholesterol, log-transformed high-sensitivity C-reactive protein, and baseline lung function [multivariable-adjusted HR and 95% CI; 1.57 (1.04-2.36)]. In contrast, individuals with diabetes did not have a significantly higher risk of obstructive lung function impairment [multivariable-adjusted HR and 95% CI; 0.93 (0.72-1.21)]. Diabetes was associated with restrictive lung function impairment but not obstructive lung function impairment. Copyright © 2017. Published by Elsevier Inc.

Augmenting autophagy for prognosis based intervention of COPD-pathophysiology.

PubMed

Bodas, Manish; Vij, Neeraj

2017-05-04

Chronic obstructive pulmonary disease (COPD) is foremost among the non-reversible fatal ailments where exposure to tobacco/biomass-smoke and aging are the major risk factors for the initiation and progression of the obstructive lung disease. The role of smoke-induced inflammatory-oxidative stress, apoptosis and cellular senescence in driving the alveolar damage that mediates the emphysema progression and severe lung function decline is apparent, although the central mechanism that regulates these processes was unknown. To fill in this gap in knowledge, the central role of proteostasis and autophagy in regulating chronic lung disease causing mechanisms has been recently described. Recent studies demonstrate that cigarette/nicotine exposure induces proteostasis/autophagy-impairment that leads to perinuclear accumulation of polyubiquitinated proteins as aggresome-bodies, indicative of emphysema severity. In support of this concept, autophagy inducing FDA-approved anti-oxidant drugs control tobacco-smoke induced inflammatory-oxidative stress, apoptosis, cellular senescence and COPD-emphysema progression in variety of preclinical models. Hence, we propose that precise and early detection of aggresome-pathology can allow the timely assessment of disease severity in COPD-emphysema subjects for prognosis-based intervention. While intervention with autophagy-inducing drugs is anticipated to reduce alveolar damage and lung function decline, resulting in a decrease in the current mortality rates in COPD-emphysema subjects.

Decrease of Airway Allergies After Lung Transplantation Is Associated With Reduced Basophils and Eosinophils.

PubMed

Niedzwiecki, M; Yamada, Y; Inci, I; Weder, W; Jungraithmayr, W

2016-01-01

Allergies are hypersensitive reactions of the immune system on antigen exposure similar to immune reactions after transplantation (Tx). Their activity can change after Tx. The lung as a transplantable organ is challenged two-fold, by antigens from the blood and the air environment. Herein we analyzed if airway allergies change after lung Tx. We systematically reviewed patients' airway allergies before and after lung Tx between 1992 and 2014. The course of lymphocytes, thrombocytes, and leukocytes, among them neutrophils, eosinophils, and basophils, was analyzed in patients in whom airway allergies have changed and in whom they did not change. From 362 lung transplanted patients, 44 patients had suffered from allergies before Tx (12.2%). In 20 of these patients (45.5%), airway allergies disappeared completely within 1 year after lung Tx and were persistently absent thereafter. In these patients, basophils and eosinophils decreased significantly (P < .0012); in contrast, cells did not decrease in patients whose allergies did not disappear. Leukocytes overall, and in particular, neutrophils, decreased significantly in patients whose allergy disappeared (P < .014, P < .012, respectively). Airway allergies disappeared in almost half of cases after lung Tx. Along with this reduction, basophils and eosinophils decreased as potentially responsible cells for this phenomenon. These findings may stimulate intensified research on basophils and eosinophils as major drivers of airway allergies. Copyright © 2016 Elsevier Inc. All rights reserved.

Dietary Apigenin Exerts Immune-Regulatory Activity in Vivo by Reducing NF-κB Activity, Halting Leukocyte Infiltration and Restoring Normal Metabolic Function.

PubMed

Cardenas, Horacio; Arango, Daniel; Nicholas, Courtney; Duarte, Silvia; Nuovo, Gerard J; He, Wei; Voss, Oliver H; Gonzalez-Mejia, M Elba; Guttridge, Denis C; Grotewold, Erich; Doseff, Andrea I

2016-03-01

The increasing prevalence of inflammatory diseases and the adverse effects associated with the long-term use of current anti-inflammatory therapies prompt the identification of alternative approaches to reestablish immune balance. Apigenin, an abundant dietary flavonoid, is emerging as a potential regulator of inflammation. Here, we show that apigenin has immune-regulatory activity in vivo. Apigenin conferred survival to mice treated with a lethal dose of Lipopolysaccharide (LPS) restoring normal cardiac function and heart mitochondrial Complex I activity. Despite the adverse effects associated with high levels of splenocyte apoptosis in septic models, apigenin had no effect on reducing cell death. However, we found that apigenin decreased LPS-induced apoptosis in lungs, infiltration of inflammatory cells and chemotactic factors' accumulation, re-establishing normal lung architecture. Using NF-κB luciferase transgenic mice, we found that apigenin effectively modulated NF-κB activity in the lungs, suggesting the ability of dietary compounds to exert immune-regulatory activity in an organ-specific manner. Collectively, these findings provide novel insights into the underlying immune-regulatory mechanisms of dietary nutraceuticals in vivo.

Reproducibility of tumor motion probability distribution function in stereotactic body radiation therapy of lung cancer.

PubMed

Zhang, Fan; Hu, Jing; Kelsey, Chris R; Yoo, David; Yin, Fang-Fang; Cai, Jing

2012-11-01

To evaluate the reproducibility of tumor motion probability distribution function (PDF) in stereotactic body radiation therapy (SBRT) of lung cancer using cine megavoltage (MV) images. Cine MV images of 20 patients acquired during three-dimensional conformal (6-11 beams) SBRT treatments were retrospectively analyzed to extract tumor motion trajectories. For each patient, tumor motion PDFs were generated per fraction (PDF(n)) using three selected "usable" beams. Patients without at least three usable beams were excluded from the study. Fractional PDF reproducibility (R(n)) was calculated as the Dice similarity coefficient between PDF(n) to a "ground-truth" PDF (PDF(g)), which was generated using the selected beams of all fractions. The mean of R(n), labeled as R(m), was calculated for each patient and correlated to the patient's mean tumor motion rang (A(m)). Change of R(m) during the course of SBRT treatments was also evaluated. Intra- and intersubject coefficient of variation (CV) of R(m) and A(m) were determined. Thirteen patients had at least three usable beams and were analyzed. The mean of R(m) was 0.87 (range, 0.84-0.95). The mean of A(m) was 3.18 mm (range, 0.46-7.80 mm). R(m) was found to decrease as A(m) increases following an equation of R(m) = 0.17e(-0.9Am) + 0.84. R(m) also decreased slightly throughout the course of treatments. Intersubject CV of R(m) (0.05) was comparable to intrasubject CV of R(m) (range, 0.02-0.09); intersubject CV of A(m) (0.73) was significantly greater than intrasubject CV of A(m) (range, 0.09-0.24). Tumor motion PDF can be determined using cine MV images acquired during the treatments. The reproducibility of lung tumor motion PDF decreased exponentially as the tumor motion range increased and decreased slightly throughout the course of the treatments. Copyright © 2012 Elsevier Inc. All rights reserved.

Effects of bronchoscopy on lung function in asthmatics.

PubMed

Bellinger, Christina; Bleecker, Eugene R; Peters, Stephen; Pascual, Rodolfo; Krings, Jeffrey; Smith, Regina; Hastie, Annette T; Moore, Wendy C

2017-10-01

To better understand the changes in pulmonary physiology related to asthma severity following bronchoscopy, we performed scheduled pre- and post-procedure spirometry on subjects undergoing bronchoscopy in our research program. Control subjects and asthma subjects were recruited for bronchoscopy. On the day of bronchoscopy, subjects underwent spirometry pre-bronchoscopy and then up to three sets within 2 hour following the completion of bronchoscopy. A subset of patients had a second bronchoscopy after 2 weeks of treatment with oral prednisolone (40mg daily). A total of 92 subjects had at least one bronchoscopy (12 control subjects, 56 nonsevere asthma (NSA), 24 severe asthma (SA)). The SA and NSA groups had similar decreases in forced expiratory volume in 1 second (FEV1) (-20±13% vs.-19±16%, p = 0.92) and forced vital capacity (FVC) (-20±12% vs.-20±14%, p = 0.80), but no change in FEV1/FVC ratio. The control and NSA group had more rapid recovery of both FEV1 and FVC by 2 hour compared to the SA group (p = 0.01). In the subset of 36 subjects (22 NSA, 14 SA) who underwent a second bronchoscopy following the administration of oral prednisolone for 14 days, steroids resulted in more rapid recovery of lung function (p < 0.04). Following bronchoscopy the lung function of NSA subjects recovered more quickly than SA subjects. Treatment with oral corticosteroids was associated with a quicker recovery of FEV1 which suggests an inflammatory mechanism for these changes in lung compliance.

Respiratory Effects of Fine and Ultrafine Particles from Indoor Sources—A Randomized Sham-Controlled Exposure Study of Healthy Volunteers

PubMed Central

Soppa, Vanessa J.; Schins, Roel P. F.; Hennig, Frauke; Hellack, Bryan; Quass, Ulrich; Kaminski, Heinz; Kuhlbusch, Thomas A. J.; Hoffmann, Barbara; Weinmayr, Gudrun

2014-01-01

Particulate air pollution is linked to impaired respiratory health. We analyzed particle emissions from common indoor sources (candles burning (CB), toasting bread (TB), frying sausages (FS)) and lung function in 55 healthy volunteers (mean age 33.0 years) in a randomized cross-over controlled exposure study. Lung-deposited particle surface area concentration (PSC), size-specific particle number concentration (PNC) up to 10 µm, and particle mass concentration (PMC) of PM1, PM2.5 and PM10 were determined during exposure (2 h). FEV1, FVC and MEF25%–75% was measured before, 4 h and 24 h after exposure. Wilcoxon-rank sum tests (comparing exposure scenarios) and mixed linear regression using particle concentrations and adjusting for personal characteristics, travel time and transportation means before exposure sessions were performed. While no effect was seen comparing the exposure scenarios and in the unadjusted model, inverse associations were found for PMC from CB and FS in relation to FEV1 and MEF25%–75%. with a change in 10 µg/m3 in PM2.5 from CB being associated with a change in FEV1 of −19 mL (95%-confidence interval:−43; 5) after 4 h. PMC from TB and PNC of UFP were not associated with lung function changes, but PSC from CB was. Elevated indoor fine particles from certain sources may be associated with small decreases in lung function in healthy adults. PMID:25000149

Pulmonary Responses in Healthy Young Adults Exposed to Low Concentration of Ozone for 6.6 Hours with Mild Exercise

EPA Science Inventory

Rational: Recent studies have shown small but significant decreases in lung function following a prolonged exposure (6.6 hour) of healthy young adults to levels of ozone (0.08 ppm) near the current 8 hour standard. It is unclear, however, if such effects may be extended to concen...

Reducing Children's Exposure to School Bus Diesel Exhaust in One School District in North Carolina

ERIC Educational Resources Information Center

Mazer, Mary E.; Jacobson Vann, Julie C.; Lamanna, Beth F.; Davison, Jean

2014-01-01

Children who are exposed to diesel exhaust from idling school buses are at increased risk of asthma exacerbation, decreased lung function, immunologic reactions, leukemia, and increased susceptibility to infections. Policies and initiatives that aim to protect school children from the harmful effects of exposure to diesel exhaust range from…

Regional Emphysema Score Predicting Overall Survival, Quality of Life and Pulmonary Function Recovery in Early-stage Lung Cancer Patients

PubMed Central

Dai, Jie; Liu, Ming; Swensen, Stephen J.; Stoddard, Shawn M.; Wampfler, Jason A.; Limper, Andrew H.; Jiang, Gening; Yang, Ping

2017-01-01

Introduction Pulmonary emphysema is a common comorbidity in lung cancer, but its role in tumor prognosis remains obscure. Our aim was to evaluate the impact of the regional emphysema score (RES) on patient’s overall survival, quality of life (QOL), and pulmonary function recovery in stage I–II lung cancer. Methods Between 1997 and 2009, 1,073 patients were identified and divided into two surgical groups (cancer in emphysematous [group 1, n=565] and non-emphysematous [group 2, n=435] region) and one non-surgical group (group 3, n=73). RES was derived from the emphysematous region and categorized into mild (≤5%), moderate (6–24%) and severe (25–60%). Results In group 1, patients with moderate and severe RES experienced slight decreases in postoperative FEV1, but increases in FEV1/FVC, compared to those with mild RES (p<0.01); however, this correlation was not observed in group 2. Post-treatment QOL was lower in patients with greater RES in all groups mainly due to dyspnea (p<0.05). Cox-regression analysis revealed that patients with higher RES had a significantly poorer survival in both surgical groups, with adjusted HRs of 1.41 and 1.43 for moderate RES and 1.63 and 2.04 for severe RES, respectively; however, this association was insignificant in the non-surgical group (adjusted HR of 0.99 for moderate/severe RES). Conclusions In surgically-treated patients with cancer in emphysematous region, RES is associated with postoperative changes in lung function. RES is also predictive of post-treatment QOL related to dyspnea in early-stage lung cancer. In both surgical groups, RES is an independent predictor of survival. PMID:28126539

Postnatal lung mechanics, lung composition, and surfactant synthesis after tracheal occlusion vs prenatal intrapulmonary instillation of perfluorocarbon in fetal rabbits.

PubMed

Muensterer, Oliver J; Flemmer, Andreas W; Bergmann, Florian; Hajek, Kerstin S; Lu, Hui Qi; Simbruner, Georg; Deprest, Jan A; Till, Holger

2005-01-01

Fetal tracheal occlusion (TO) accelerates lung growth but decreases surfactant production. We have previously shown that instillation of perfluorooctylbromide (PFOB) into fetal rabbit lungs leads to lung growth similar to TO. This study compares neonatal lung mechanics and surfactant production after prenatal intrapulmonary PFOB instillation vs TO. In each of 18 pregnant rabbits on gestational day 27, sets of 4 fetuses underwent either (1) intrapulmonary instillation of 1 mL PFOB, (2) TO, (3) instillation of 1 mL 0.9% NaCl (saline), and (4) hysteroamniotomy without fetal manipulation (control). Fetuses were born by cesarean delivery after 48 hours. Fetuses of 12 rabbits were mechanically ventilated for 15 minutes to evaluate lung compliance and airway resistance. Pulmonary surfactant protein B (SP-B) was quantified by immunohistochemistry in fetuses of the remaining 6 rabbits. Compliance was decreased in the TO group after cesarean delivery (0.33 +/- 0.13 mL/cm H2O) compared with PFOB (0.59 +/- 0.12 mL/cm H2O), saline (0.50 +/- 0.12 mL/cm H2O), and control (0.52 +/- 0.10 mL/cm H2O) fetuses. Mean fetal lung to body weight ratio was higher in TO and PFOB fetuses compared with saline and control. Higher water content and lower numbers of surfactant protein B-positive cells were found in the TO-treated fetuses. Both prenatal intrapulmonary instillation of PFOB and TO accelerate lung growth, but TO is associated with decreased postnatal lung compliance, possibly influenced by decreased surfactant production and increased fluid retention. Conversely, instillation of PFOB preserved lung compliance and surfactant synthesis.

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 processes. PMID:25178924

[A rare form of obstructive pulmonary disease].

PubMed

van Loenhout, C J; den Bakker, M A; van Wijsenbeek, M S; Hoek, R A S; van Hal, P Th W

2016-01-01

Lymphangioleiomyomatosis (LAM) is characterised by progressive dyspnoea, spontaneous pneumothorax and cystic pulmonary destruction. The disease may show similarities with emphysema clinically, radiologically and on lung function tests. A 44-year-old woman was referred for lung transplantation because of a 6-year history of dyspnoea and severe obstructive pulmonary function disorder with decreased diffusion capacity. Both her relatively young age and the fact that she had never smoked made us doubt the diagnosis 'COPD'. The pulmonary cysts seen on high-resolution CT (HRCT) suggested LAM. This was confirmed when we revised a pulmonary biopsy that had previously been performed. CT investigation should be carried out in patients with severe obstructive pulmonary disease without a risk profile appropriate for COPD. Diffuse, homogenous cysts on CT scan can indicate LAM, particularly in women. Conflict of interest and financial support: none declared.

Critical role of CXCL4 in the lung pathogenesis of influenza (H1N1) respiratory infection.

PubMed

Guo, L; Feng, K; Wang, Y C; Mei, J J; Ning, R T; Zheng, H W; Wang, J J; Worthen, G S; Wang, X; Song, J; Li, Q H; Liu, L D

2017-11-01

Annual epidemics and unexpected pandemics of influenza are threats to human health. Lung immune and inflammatory responses, such as those induced by respiratory infection influenza virus, determine the outcome of pulmonary pathogenesis. Platelet-derived chemokine (C-X-C motif) ligand 4 (CXCL4) has an immunoregulatory role in inflammatory diseases. Here we show that CXCL4 is associated with pulmonary influenza infection and has a critical role in protecting mice from fatal H1N1 virus respiratory infection. CXCL4 knockout resulted in diminished viral clearance from the lung and decreased lung inflammation during early infection but more severe lung pathology relative to wild-type mice during late infection. Additionally, CXCL4 deficiency decreased leukocyte accumulation in the infected lung with markedly decreased neutrophil infiltration into the lung during early infection and extensive leukocyte, especially lymphocyte accumulation at the late infection stage. Loss of CXCL4 did not affect the activation of adaptive immune T and B lymphocytes during the late stage of lung infection. Further study revealed that CXCL4 deficiency inhibited neutrophil recruitment to the infected mouse lung. Thus the above results identify CXCL4 as a vital immunoregulatory chemokine essential for protecting mice against influenza A virus infection, especially as it affects the development of lung injury and neutrophil mobilization to the inflamed lung.

[Clinical laboratory tests supporting respiratory disease treatment--chairman's introductory remarks].

PubMed

Takai, Daiya

2014-12-01

The symposium consisted of four parts: history of lung function tests, nitric oxide for diagnosis and monitoring of bronchial asthma, radiological and functional changes of the lung in COPD, and combined pulmonary fibrosis and emphysema (CPFE) occasionally showing almost normal results in lung function tests. The history of lung function tests was presented by Dr. Naoko Tojo of the Tokyo Medical and Dental University. Nitric oxide tests in clinical use for diagnosis and monitoring of bronchial asthma were presented by Dr. Hiroyuki Nagase of Teikyo University. Radiological and functional changes of the lung in COPD were presented by Dr. Shigeo Muro of Kyoto University. Clinical features of combined pulmonary fibrosis and emphysema and their associated lung function were presented by Dr. Daiya Takai of the University of Tokyo. I hope that discussing the history of lung function tests until the present was useful for many medical technologists. (Review).

Xeroderma Pigmentosum Group C Deficiency Alters Cigarette Smoke DNA Damage Cell Fate and Accelerates Emphysema Development.

PubMed

Sears, Catherine R; Zhou, Huaxin; Justice, Matthew J; Fisher, Amanda J; Saliba, Jacob; Lamb, Isaac; Wicker, Jessica; Schweitzer, Kelly S; Petrache, Irina

2018-03-01

Cigarette smoke (CS) exposure is a major risk factor for the development of emphysema, a common disease characterized by loss of cells comprising the lung parenchyma. The mechanisms of cell injury leading to emphysema are not completely understood but are thought to involve persistent cytotoxic or mutagenic DNA damage induced by CS. Using complementary cell culture and mouse models of CS exposure, we investigated the role of the DNA repair protein, xeroderma pigmentosum group C (XPC), on CS-induced DNA damage repair and emphysema. Expression of XPC was decreased in mouse lungs after chronic CS exposure and XPC knockdown in cultured human lung epithelial cells decreased their survival after CS exposure due to activation of the intrinsic apoptosis pathway. Similarly, cell autophagy and apoptosis were increased in XPC-deficient mouse lungs and were further increased by CS exposure. XPC deficiency was associated with structural and functional changes characteristic of emphysema, which were worsened by age, similar to levels observed with chronic CS exposure. Taken together, these findings suggest that repair of DNA damage by XPC plays an important and previously unrecognized role in the maintenance of alveolar structures. These findings support that loss of XPC, possibly due to chronic CS exposure, promotes emphysema development and further supports a link between DNA damage, impaired DNA repair, and development of emphysema.

Effects of tiotropium on lung hyperinflation, dyspnoea and exercise tolerance in COPD.

PubMed

O'Donnell, D E; Flüge, T; Gerken, F; Hamilton, A; Webb, K; Aguilaniu, B; Make, B; Magnussen, H

2004-06-01

The aim of this study was to test the hypothesis that use of tiotropium, a new long-acting anticholinergic bronchodilator, would be associated with sustained reduction in lung hyperinflation and, thereby, would improve exertional dyspnoea and exercise performance in patients with chronic obstructive pulmonary disease. A randomised, double-blind, placebo-controlled, parallel-group study was conducted in 187 patients (forced expiratory volume in one second 44 +/- 13% pred): 96 patients received 18 microg tiotropium and 91 patients received placebo once daily for 42 days. Spirometry, plethysmographic lung volumes, cycle exercise endurance and exertional dyspnoea intensity at 75% of each patient's maximal work capacity were compared. On day 42, the use of tiotropium was associated with the following effects at pre-dose and post-dose measurements as compared to placebo: vital capacity and inspiratory capacity (IC) increased, with inverse decreases in residual volume and functional residual capacity. Tiotropium increased post-dose exercise endurance time by 105 +/- 40 s (21%) as compared to placebo on day 42. At a standardised time near end-exercise (isotime), IC, tidal volume and minute ventilation all increased, whilst dyspnoea decreased by 0.9 +/- 0.3 Borg scale units. In conclusion, the use of tiotropium was associated with sustained reductions of lung hyperinflation at rest and during exercise. Resultant increases in inspiratory capacity permitted greater expansion of tidal volume and contributed to improvements in both exertional dyspnoea and exercise endurance.

From the Journal archives: Airway closure and lung volumes in surgical positions.

PubMed

Grocott, Hilary P

2014-04-01

Douglas B. Craig, W.M. Wahba, Hillary Don Can Anaesth Soc J 1971; 18: 92-9. Surgery and anesthesia expose patients to moderate and sometimes extreme positioning changes that are often unphysiological. The purpose of this article is to highlight and contextualize a seminal study from the Journal archives that explores the effect of several commonly utilized surgical positions (supine, Trendelenburg and lithotomy) and age on basic lung volumes as well as the volume at which small airway closure (AC) (also known as closing volume [CV]) occurs. These factors were examined with the aim of determining which patient position variables could be of clinical significance to gas exchange in the perioperative period. This work showed that supine positioning, when compared with the seated position, results in a decrease of all lung volumes and capacities, including functional residual capacity (FRC) and CV. Trendelenburg positioning further decreases FRC, with no further changes induced by lithotomy positioning. Age is a clinically important factor in AC, occurring within the tidal volume range at a lower age when supine as compared with the seated position. The work of Drs. D. Craig et al. published in the Journal more than 40 years ago was seminal to our understanding of how patient positioning has an important influence on lung volumes and on the age-related relationship between FRC and CV.

Overexpression of TMPRSS4 in non-small cell lung cancer is associated with poor prognosis in patients with squamous histology

PubMed Central

Larzabal, L; Nguewa, P A; Pio, R; Blanco, D; Sanchez, B; Rodríguez, M J; Pajares, M J; Catena, R; Montuenga, L M; Calvo, A

2011-01-01

Background: Mortality rates in lung cancer patients have not decreased significantly in recent years, even with the implementation of new therapeutic regimens. One of the main problems is that a large proportion of patients present local or distant metastasis at the time of diagnosis. The need for identification of novel biomarkers and therapeutic targets for a more effective management of lung cancer led us to investigate TMPRSS4, a protease reported to promote tumour growth and metastasis. Material and methods: In all, 34 lung cancer cell lines were used to evaluate the TMPRSS4 expression. Cell migration and clonogenic assays, and an in-vivo lung metastasis model were used for functional analysis of the TMPRSS4 downregulation in H358, H441 and H2170 cell lines. The TMPRSS4 expression analysis in normal and malignant lung tissue samples was performed by qPCR. Five different microarray-based publicly available expression databases were used to validate our results and to study prognosis. Results: The TMPRSS4 knock down in H358, H441 and H2170 cells resulted in a significant reduction in proliferation, clonogenic capacity and invasion. A significant (P<0.05) decrease in the lung colonisation and growth was found when mice were injected with TMPRSS4-depleated H358-derived clones, as compared with controls. Expression of TMPRSS4 showed a >30-fold increase (P<0.001) in tumours in comparison with non-malignant samples. Levels in tumours with squamous cell carcinoma (SCC) histology were found to be significantly higher (P<0.001) than those with adenocarcinoma (AC) histology, which was confirmed in data retrieved from the microarrays. Kaplan–Meier curves demonstrated that high levels of TMPRSS4 were significantly associated (P=0.017) with reduced overall survival in the patients with SCC histology, whereas no correlation was found for the AC histology. Conclusion: Our results demonstrate that TMPRSS4 has a role in the lung cancer development. The potential use of TMPRSS4 as a biomarker for lung cancer detection or as a predictor of patient's outcome warrants further investigation. PMID:22067904

Physiologic Evaluation of Ventilation Perfusion Mismatch and Respiratory Mechanics at Different Positive End-expiratory Pressure in Patients Undergoing Protective One-lung Ventilation.

PubMed

Spadaro, Savino; Grasso, Salvatore; Karbing, Dan Stieper; Fogagnolo, Alberto; Contoli, Marco; Bollini, Giacomo; Ragazzi, Riccardo; Cinnella, Gilda; Verri, Marco; Cavallesco, Narciso Giorgio; Rees, Stephen Edward; Volta, Carlo Alberto

2018-03-01

Arterial oxygenation is often impaired during one-lung ventilation, due to both pulmonary shunt and atelectasis. The use of low tidal volume (VT) (5 ml/kg predicted body weight) in the context of a lung-protective approach exacerbates atelectasis. This study sought to determine the combined physiologic effects of positive end-expiratory pressure and low VT during one-lung ventilation. Data from 41 patients studied during general anesthesia for thoracic surgery were collected and analyzed. Shunt fraction, high V/Q and respiratory mechanics were measured at positive end-expiratory pressure 0 cm H2O during bilateral lung ventilation and one-lung ventilation and, subsequently, during one-lung ventilation at 5 or 10 cm H2O of positive end-expiratory pressure. Shunt fraction and high V/Q were measured using variation of inspired oxygen fraction and measurement of respiratory gas concentration and arterial blood gas. The level of positive end-expiratory pressure was applied in random order and maintained for 15 min before measurements. During one-lung ventilation, increasing positive end-expiratory pressure from 0 cm H2O to 5 cm H2O and 10 cm H2O resulted in a shunt fraction decrease of 5% (0 to 11) and 11% (5 to 16), respectively (P < 0.001). The PaO2/FIO2 ratio increased significantly only at a positive end-expiratory pressure of 10 cm H2O (P < 0.001). Driving pressure decreased from 16 ± 3 cm H2O at a positive end-expiratory pressure of 0 cm H2O to 12 ± 3 cm H2O at a positive end-expiratory pressure of 10 cm H2O (P < 0.001). The high V/Q ratio did not change. During low VT one-lung ventilation, high positive end-expiratory pressure levels improve pulmonary function without increasing high V/Q and reduce driving pressure.

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

2016-07-27

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.

Association between lung function and mental health problems among adults in the United States: findings from the First National Health and Nutrition Examination Survey.

PubMed

Goodwin, Renee D; Chuang, Shirley; Simuro, Nicole; Davies, Mark; Pine, Daniel S

2007-02-15

The objective of this study was to determine the association between lung function and mental health problems among adults in the United States. Data were drawn from the First National Health and Nutrition Examination Survey (1971-1975), with available information on a representative sample of US adults aged 25-74 years. Lung function was assessed by spirometry, and provisional diagnoses of restrictive and obstructive airway disease were assigned based on percentage of expected forced expiratory volume. Mental health problems were assessed with the General Well-Being scales. Restrictive lung function and obstructive lung function, compared with normal lung function, were each associated with a significantly increased likelihood of mental health problems. After adjustment for differences in demographic characteristics, obstructive lung function was associated with significantly lower overall well-being (p = 0.025), and restrictive lung function was associated with significantly lower overall well-being (p < 0.001), general health (p < 0.0001), vitality (p < 0.0001), and self-control (p = 0.001) and with higher depression (p = 0.002) subscale scores compared with no lung function problems. Consistent with previous findings from clinical and community-based studies, these results extend available data by providing evidence of a link between objectively measured lung function and self-reported mental health problems in a representative sample of community adults. Future studies are needed to determine the mechanisms of these associations.

Effect of indoor air pollution on the respiratory system of women using different fuels for cooking in an urban slum of Pondicherry.

PubMed

Dutt, D; Srinivasa, D K; Rotti, S B; Sahai, A; Konar, D

1996-01-01

Some of the highest exposures to air pollutants in developing countries occur inside homes where biofuels are used for daily cooking. Inhalation of these pollutants may cause deleterious effects on health. We studied the effects of exposure to indoor air pollution from the use of cooking fuels on lung functions and respiratory symptoms in women aged 15-60 years. The study was conducted in Kuruchikuppam, an urban slum in Pondicherry. The study participants were 105 women using biofuels, 105 using kerosene and 105 using liquid petroleum gas (LPG), selected from among 1117 women aged 15-60 years, by a stratified random sampling technique. These women were interviewed at home to collect information about exposure to fuel smoke and presence of respiratory symptoms. Lung functions were assessed by measuring forced vital capacity (FVC), forced expiratory volume in the first second (FEV1) and peak expiratory flow rate (PEFR). Occurrence of respiratory symptoms over six months was noted by making monthly follow up visits. Women using biofuels experienced more respiratory symptoms (23%) than those using kerosene (13%;p > 0.05) or LPG (8%; p < 0.05). Lung functions-FVC, FEV1, FEV1% and PEFR-were significantly lower in biofuel users compared with both kerosene (p < 0.01) and LPG users (p < 0.001). Lung functions in kerosene users also were significantly poorer when compared with LPG users (p < 0.01). Predicted pulmonary functions using multiple regression equations, derived from the data set of the present study, indicated that women using biofuels were more liable to have reduced pulmonary functions than women using kerosene or LPG. Women exposed to biofuel smoke suffer more from respiratory illnesses and have decreased pulmonary functions compared with women exposed to kerosene or LPG smoke. To reduce pollutant exposures we recommend the use of smokeless chullas or cleaner fuels such as charcoal, biogas and kerosene.

Polydatin protects the respiratory system from PM2.5 exposure.

PubMed

Yan, Xiao-Dan; Wang, Qi-Ming; Tie, Cai; Jin, Hong-Tao; Han, Yan-Xing; Zhang, Jin-Lan; Yu, Xiao-Ming; Hou, Qi; Zhang, Piao-Piao; Wang, Ai-Ping; Zhang, Pei-Cheng; Gao, Zhonggao; Jiang, Jian-Dong

2017-01-09

Atmospheric particle is one of the risk factors for respiratory disease; however, their injury mechanisms are poorly understood, and prevention methods are highly desirable. We constructed artificial PM 2.5 (aPM 2.5 ) particles according to the size and composition of actual PM 2.5 collected in Beijing. Using these artificial particles, we created an inhalation-injury animal model. These aPM 2.5 particles simulate the physical and chemical characteristics of the actual PM 2.5 , and inhalation of the aPM 2.5 in rat results in a time-dependent change in lung suggesting a declined lung function, injury from oxidative stress and inflammation in lung. Thus, this aPM 2.5 -caused injury animal model may mimic that of the pulmonary injury in human exposed to airborne particles. In addition, polydatin (PD), a resveratrol glucoside that is rich in grapes and red wine, was found to significantly decrease the oxidative potential (OP) of aPM 2.5 in vitro. Treating the model rats with PD prevented the lung function decline caused by aPM 2.5 , and reduced the level of oxidative damage in aPM 2.5 -exposed rats. Moreover, PD inhibited aPM 2.5 -induced inflammation response, as evidenced by downregulation of white blood cells in bronchoalveolar lavage fluid (BALF), inflammation-related lipids and proinflammation cytokines in lung. These results provide a practical means for self-protection against particulate air pollution.

Polydatin protects the respiratory system from PM2.5 exposure

PubMed Central

Yan, Xiao-Dan; Wang, Qi-Ming; Tie, Cai; Jin, Hong-Tao; Han, Yan-Xing; Zhang, Jin-Lan; Yu, Xiao-Ming; Hou, Qi; Zhang, Piao-Piao; Wang, Ai-Ping; Zhang, Pei-Cheng; Gao, Zhonggao; Jiang, Jian-Dong

2017-01-01

Atmospheric particle is one of the risk factors for respiratory disease; however, their injury mechanisms are poorly understood, and prevention methods are highly desirable. We constructed artificial PM2.5 (aPM2.5) particles according to the size and composition of actual PM2.5 collected in Beijing. Using these artificial particles, we created an inhalation-injury animal model. These aPM2.5 particles simulate the physical and chemical characteristics of the actual PM2.5, and inhalation of the aPM2.5 in rat results in a time-dependent change in lung suggesting a declined lung function, injury from oxidative stress and inflammation in lung. Thus, this aPM2.5-caused injury animal model may mimic that of the pulmonary injury in human exposed to airborne particles. In addition, polydatin (PD), a resveratrol glucoside that is rich in grapes and red wine, was found to significantly decrease the oxidative potential (OP) of aPM2.5 in vitro. Treating the model rats with PD prevented the lung function decline caused by aPM2.5, and reduced the level of oxidative damage in aPM2.5-exposed rats. Moreover, PD inhibited aPM2.5-induced inflammation response, as evidenced by downregulation of white blood cells in bronchoalveolar lavage fluid (BALF), inflammation-related lipids and proinflammation cytokines in lung. These results provide a practical means for self-protection against particulate air pollution. PMID:28067267

CCL21 and IP-10 as blood biomarkers for pulmonary involvement in systemic lupus erythematosus patients.

PubMed

Odler, B; Bikov, A; Streizig, J; Balogh, C; Kiss, E; Vincze, K; Barta, I; Horváth, I; Müller, V

2017-05-01

Biomarkers for pulmonary manifestations in systemic lupus erythematosus (SLE) are missing. Plasma samples of nine SLE patients with known pulmonary involvement (SLE pulm ) and nine SLE patients without pulmonary involvement (SLE) were tested by multiplex microarray analysis for various cyto- and chemokines. Significantly decreased lung function paramters for forced vital capacity (FVC), total lung capacity (TLC), diffusion capacity for carbon monoxide (DL CO ) and diffusion of CO corrected on lung volume (KL CO ) were observed in SLE pulm as compared to SLE patients. CC chemokine ligand 21 (CCL21) and interferon gamma-induced protein 10 (IP-10) levels were significantly higher in SLE pulm , than in patients without pulmonary manifestations. CCL21 correlated negatively with DL CO ( r = -0.73; p < 0.01) and KL CO ( r = -0.62; p < 0.01), while IP-10 with FVC and forced expiratory volume one second. Receiver Operating Characteristics (ROC) analysis confirmed high sensitivity and specificity for the separation of SLE patients with and without pulmonary involvement for the chemokines CCL21 (Area Under Curve (AUC): 0.85; sensitivity%: 88.90; specificity%: 75.00; p < 0.01) and IP-10 (AUC: 0.82; sensitivity%: 66.67, specificity%: 100; p < 0.01). Pleuropulmonary manifestations in SLE patients associated with lung functional and DL CO /KL CO changes and were associated with significant increase in CCL21 and IP-10. These chemokines might serve as potential biomarkers of lung involvement in SLE patients.

Prevention of abnormal pulmonary mechanics in the postmortem guinea pig lung.

PubMed

Reynolds, A M; McEvoy, R D

1988-04-01

Severe postmortem bronchoconstriction has been shown previously in guinea pig lungs and linked to pulmonary blood loss during exsanguination (Lai et al., J. Appl. Physiol. 56: 308-314, 1984). To reexamine this phenomenon we measured postmortem airway function in anesthetized open-chest guinea pigs after sudden circulatory arrest. Animals were divided into 4 groups of 10 and ventilated for 15 min postmortem with different gases: 1) room air, 2) conditioned air, 3) dry 5% CO2-21% O2-74% N2, and 4) conditioned 5% CO2-21% O2-74% N2. In room air-ventilated lungs there was a 50% decrease in dynamic compliance (Cdyn) by 15 min and marked gas trapping compared with control lungs. Conditioning the room air did not attenuate these changes, but when 5% CO2 was added to the conditioned postmortem inspirate, gas trapping was eliminated and the fall in Cdyn was almost abolished. Ventilation with a dry 5% CO2 gas mixture at room temperature resulted in a 31% fall in Cdyn at 15 min but no gas trapping. We conclude that marked abnormalities of airway function occur postmortem in room air-ventilated guinea pig lungs in the absence of pulmonary blood loss. The changes are mainly due to airway hypocarbia, a known cause of bronchoconstriction, but a reduction in Cdyn can also occur if there is marked airway cooling and drying. Acute postmortem airway dysfunction can be prevented in the guinea pig by maintaining normal airway gas composition.

Polydatin protects the respiratory system from PM2.5 exposure

NASA Astrophysics Data System (ADS)

Yan, Xiao-Dan; Wang, Qi-Ming; Tie, Cai; Jin, Hong-Tao; Han, Yan-Xing; Zhang, Jin-Lan; Yu, Xiao-Ming; Hou, Qi; Zhang, Piao-Piao; Wang, Ai-Ping; Zhang, Pei-Cheng; Gao, Zhonggao; Jiang, Jian-Dong

2017-01-01

Atmospheric particle is one of the risk factors for respiratory disease; however, their injury mechanisms are poorly understood, and prevention methods are highly desirable. We constructed artificial PM2.5 (aPM2.5) particles according to the size and composition of actual PM2.5 collected in Beijing. Using these artificial particles, we created an inhalation-injury animal model. These aPM2.5 particles simulate the physical and chemical characteristics of the actual PM2.5, and inhalation of the aPM2.5 in rat results in a time-dependent change in lung suggesting a declined lung function, injury from oxidative stress and inflammation in lung. Thus, this aPM2.5-caused injury animal model may mimic that of the pulmonary injury in human exposed to airborne particles. In addition, polydatin (PD), a resveratrol glucoside that is rich in grapes and red wine, was found to significantly decrease the oxidative potential (OP) of aPM2.5 in vitro. Treating the model rats with PD prevented the lung function decline caused by aPM2.5, and reduced the level of oxidative damage in aPM2.5-exposed rats. Moreover, PD inhibited aPM2.5-induced inflammation response, as evidenced by downregulation of white blood cells in bronchoalveolar lavage fluid (BALF), inflammation-related lipids and proinflammation cytokines in lung. These results provide a practical means for self-protection against particulate air pollution.

Screening for Chronic Obstructive Pulmonary Disease (COPD) in an Urban HIV Clinic: A Pilot Study

PubMed Central

Kaner, Robert J.; Glesby, Marshall J.

2015-01-01

Abstract Increased smoking and a detrimental response to tobacco smoke in the lungs of HIV/AIDS patients result in an increased risk for COPD. We aimed to determine the predictive value of a COPD screening strategy validated in the general population and to identify HIV-related factors associated with decreased lung function. Subjects at least 35 years of age at an HIV clinic in New York City completed a COPD screening questionnaire and peak flow measurement. Those with abnormal results and a random one-third of normal screens had spirometry. 235 individuals were included and 89 completed spirometry. Eleven (12%) had undiagnosed airway obstruction and 5 had COPD. A combination of a positive questionnaire and abnormal peak flow yielded a sensitivity of 20% (specificity 93%) for detection of COPD. Peak flow alone had a sensitivity of 80% (specificity 80%). Abnormal peak flow was associated with an AIDS diagnosis (p=0.04), lower nadir (p=0.001), and current CD4 counts (p=0.001). Nadir CD4 remained associated in multivariate analysis (p=0.05). Decreased FEV1 (<80% predicted) was associated with lower CD4 count nadir (p=0.04) and detectable current HIV viral load (p=0.01) in multivariate analysis. Questionnaire and peak flow together had low sensitivity, but abnormal peak flow shows potential as a screening tool for COPD in HIV/AIDS. These data suggest that lung function may be influenced by HIV-related factors. PMID:25723842

Physical activity, black carbon exposure, and DNA methylation in the FOXP3 promoter.

PubMed

Lovinsky-Desir, Stephanie; Jung, Kyung Hwa; Jezioro, Jacqueline R; Torrone, David Z; de Planell-Saguer, Mariangels; Yan, Beizhan; Perera, Frederica P; Rundle, Andrew G; Perzanowski, Matthew S; Chillrud, Steven N; Miller, Rachel L

2017-01-01

Physical activity is associated with improvement in lung function; however, pollution exposure during physical activity can lead to a transient reduction in lung function. This paradoxical relationship may be linked to altered T regulatory (Treg) cell activity, which increases with exercise and suppresses airway inflammation, but decreases in association with exposure to air pollution. To clarify these relationships, we investigated buccal cell DNA methylation of the forkhead box p3 ( FOXP3 ) gene promoter, a proposed biomarker of Treg activity. We hypothesized that active urban children would have lower FOXP3 promoter methylation, associated with better lung function compared to non-active children. We also hypothesized that this relationship would be attenuated by high exposure to the air pollutant black carbon (BC). We performed a cross-sectional study of 135 children ages 9-14 who live in New York City. Activity was measured across 6 days. BC exposure was assessed by personal monitors worn for two 24-h periods, followed by lung function assessment. Buccal swabs were collected for DNA methylation analysis of three regions (six CpG sites) in the FOXP3 promoter. In multivariable regression models, overall, there was no significant relationship between physical activity and FOXP3 promoter methylation ( p  > 0.05). However, in stratified analyses, among children with higher BC exposure (≥1200 ng/m 3 ), physical activity was associated with 2.37% lower methylation in promoter 2 (CpGs -77, -65, and -58) ( β estimate  = -2.37%, p  < 0.01) but not among those with lower BC exposure ( β estimate  = 0.54%, p  > 0.05). Differences across strata were statistically significant ( p interaction  = 0.04). Among all children, after controlling for BC concentration, promoter 2 methylation was associated with reduced FEV 1 /FVC ( β estimate  = -0.40%, p  < 0.01) and reduced FEF 25-75% ( β estimate  = -1.46%, p  < 0.01). Physical activity in urban children appeared associated with lower FOXP3 promoter methylation, a possible indicator of greater Treg function, under conditions of high BC exposure. Reduced FOXP3 promoter methylation was associated with higher lung function. These findings suggest that physical activity may induce immunologic benefits, particularly for urban children with greater risk of impaired lung function due to exposure to higher air pollution. FOXP3 promoter buccal cell methylation may function as a useful biomarker of that benefit.

Respiratory function in healthy ever-smokers is impaired by smoking habits in a dose-dependent manner.

PubMed

Osanai, Shinobu; Ogasa, Toshiyuki; Sumitomo, Kazuhiro; Hasebe, Naoyuki

2018-01-01

There is limited information about the respiratory function of ever-smokers without lung disorders. We sought to assess the effects of smoking habits on respiratory function in subjects without lung disorders. Subjects were recruited from among patients without any evidence of respiratory disorders who visited rural primary care clinics. Each participant was asked to answer a questionnaire that included questions smoking history. Their forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were measured. We analyzed 802 subjects (364 men and 438 women). The means of the lambda-mu-sigma method derived z-score of FEV1 (zFEV1) both in current-smokers and ex-smokers were lower than that in never-smokers. The mean zFEV1 in the ever-smokers with more than 30 pack-years of smoking history were lower than that in the ever-smokers with less smoking history. Univariate analysis showed that there were significant negative correlations between pack-years and zFEV1 both in the ex-smokers and current-smokers. There was no significant correlation between the duration of smoking cessation and zFEV1 in the ex-smokers. Our data suggests that respiratory function in healthy ever-smokers is decreased based on smoking habits in a dose-dependent manner. Even after a long period of smoking cessation, the decreased respiratory function seems to be maintained in ex-smokers. Copyright © 2017 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

Quantification of lung microstructure with hyperpolarized 3He diffusion MRI

PubMed Central

Sukstanskii, Alexander L.; Woods, Jason C.; Gierada, David S.; Quirk, James D.; Hogg, James C.; Cooper, Joel D.; Conradi, Mark S.

2009-01-01

The structure and integrity of pulmonary acinar airways and their changes in different diseases are of great importance and interest to a broad range of physiologists and clinicians. The introduction of hyperpolarized gases has opened a door to in vivo studies of lungs with MRI. In this study we demonstrate that MRI-based measurements of hyperpolarized 3He diffusivity in human lungs yield quantitative information on the value and spatial distribution of lung parenchyma surface-to-volume ratio, number of alveoli per unit lung volume, mean linear intercept, and acinar airway radii—parameters that have been used by lung physiologists for decades and are accepted as gold standards for quantifying emphysema. We validated our MRI-based method in six human lung specimens with different levels of emphysema against direct unbiased stereological measurements. We demonstrate for the first time MRI images of these lung microgeometric parameters in healthy lungs and lungs with different levels of emphysema (mild, moderate, and severe). Our data suggest that decreases in lung surface area per volume at the initial stages of emphysema are due to dramatic decreases in the depth of the alveolar sleeves covering the alveolar ducts and sacs, implying dramatic decreases in the lung's gas exchange capacity. Our novel methods are sufficiently sensitive to allow early detection and diagnosis of emphysema, providing an opportunity to improve patient treatment outcomes, and have the potential to provide safe and noninvasive in vivo biomarkers for monitoring drug efficacy in clinical trials. PMID:19661452

Radiation injury in rat lung: I. Prostacyclin (PGI/sub 2/) production, arterial perfusion, and ultrastructure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ts'ao, C.; Ward, W.F.; Port, C.D.

1983-11-01

Pulmonary prostacyclin (PGI/sub 2/) production, arterial perfusion, and ultrastructure were correlated in rats sacrificed from 1 day to 6 months after a single exposure of 25 Gy of gamma rays to the right hemithorax. PGI/sub 2/ production by the irradiated lung decreased to approximately half the normal value 1 day after irradiation (P < 0.05), then increased steadily throughout the study. By 6 months postirradiation, the right lung produced two to three times as much PGI/sub 2/ as did either shielded left lung or sham-irradiated lungs (P < 0.05). Perfusion scans revealed hyperemia of the right lung from 1 tomore » 14 days after irradiation. From its peak at 14 days postirradiation, however, perfusion of the irradiated lung decreased steadily, then reached a plateau from 3 to 6 months at less than half that in the shielded left lung. Electron micrographs of the right lung revealed perivascular edema from 1 to 30 days after irradiation. The right lung then exhibited changes typical of radiation pneumonitis followed by progressive interstitial fibrosis. Platelet aggregates were not observed at any time. Thus, decreased PGI/sub 2/ production is an immediate but transient response of the lung to radiation injury. Then from 2 to 6 months after irradiation, the fibrotic, hypoperfused lung produces increasing amounts of the potent vasodilator and antithrombotic agent, PGI/sub 2/. Pulmonary PGI/sub 2/ production and arterial perfusion are inversely correlated for at least 6 months after hemithoracic irradiation.« less

Lung respiratory rhythm and pattern generation in the bullfrog: role of neurokinin-1 and mu-opioid receptors.

PubMed

Davies, B L; Brundage, C M; Harris, M B; Taylor, B E

2009-07-01

Location of the lung respiratory rhythm generator (RRG) in the bullfrog brainstem was investigated by examining neurokinin-1 and mu-opioid receptor (NK1R, muOR) colocalization by immunohistochemistry and characterizing the role of these receptors in lung rhythm and episodic pattern generation. NK1R and muOR occurred in brainstems from all developmental stages. In juvenile bullfrogs a distinct area of colocalization was coincident with high-intensity fluorescent labeling of muOR; high-intensity labeling of muOR was not distinctly and consistently localized in tadpole brainstems. NK1R labeling intensity did not change with development. Similarity in colocalization is consistent with similarity in responses to substance P (SP, NK1R agonist) and DAMGO (muOR agonist) when bath applied to bullfrog brainstems of different developmental stages. In early stage tadpoles and juvenile bullfrogs, SP increased and DAMGO decreased lung burst frequency. In juvenile bullfrogs, SP increased lung burst frequency, episode frequency, but decreased number of lung bursts per episode and lung burst duration. In contrast, DAMGO decreased lung burst frequency and burst cycle frequency, episode frequency, and number of lung bursts per episode but increased all other lung burst parameters. Based on these results, we hypothesize that NK1R and muOR colocalization together with a metamorphosis-related increase in muOR intensity marks the location of the lung RRG but not necessarily the lung episodic pattern generator.

Effects of immersion in cool water on lung-exhaled nitric oxide at rest and during exercise

NASA Technical Reports Server (NTRS)

Pendergast, D. R.; Krasney, J. A.; DeRoberts, D.; Farhi, L. E. (Principal Investigator)

1999-01-01

Lung nitric oxide (NO) has been postulated to relax airway and vascular smooth muscle at rest and during exercise. As a cold environment is a common cause of respiratory distress, lung exhaled NO was measured during skin and core body cooling at rest and during a progressive cycle exercise. Ten healthy male subjects were immersed in water at a water temperature (Tw) which was thermal neutral (35 degrees C) at 30 degrees C Tw, at which only skin temperature is decreased; and at 20 degrees C Tw, at which the core temperature is decreased (0.05 degrees C). At rest, V(O), and V(E) increased while exhaled NO concentration [NO] and the rate of expiration of NO (V(NO)) decreased with decreased Tw. V(O2) and ventilation (V(E)) increased with workload (W) and the values at all Tw were not different, whereas, [NO] decreased with W and the values during exercise were progressively less at all Ws as Tw declined. These results indicate that lung NO output is reduced in a graded fashion during body cooling at rest and during exercise. This suggests that lower lung NO may contribute to airway obstruction in cold environments and NO may contribute to regulation of lung heat and water exchange.

Effects of puberty on cystic fibrosis related pulmonary exacerbations in women versus men.

PubMed

Sutton, Shelby; Rosenbluth, Daniel; Raghavan, Deepa; Zheng, Jie; Jain, Raksha

2014-01-01

Epidemiologic data from studies of airway diseases, such as asthma, chronic obstructive pulmonary disease, and cystic fibrosis indicate a gender disparity where women have worse outcomes. The explanation for this is largely unknown. We hypothesize that female sex hormones play a role in this gender disparity, predisposing women to more exacerbations and decreased lung function post-puberty. In Cystic Fibrosis, to determine if puberty marks a point of increasing exacerbations and decreasing lung function in women relative to men. Using the United States Cystic Fibrosis Foundation Patient Registry, we used linear regression to compare lung function and rate of pulmonary exacerbations in men versus women before and after puberty. Of 5,137 subjects who met inclusion criteria, 2,689 were male and 2,448 were female. Average age of puberty was found to be 13.2 ± 2.2 years in men and 11.2 ± 2.0 years of age in women. Percent predicted FEV1 pre- and post-puberty were no different between males versus females (P = 0.44 pre-puberty and P = 0.16 post-puberty). In contrast, women had a significantly higher rate of pulmonary exacerbations post-puberty than men (1.17 ± 1.35 exacerbations per year in women versus 0.95 ± 1.27 in men; P < 0.001) despite controlling for morphometrics, co-morbidities, and microbiologic variables. After puberty, the rate of pulmonary exacerbations increased in adolescent women relative to men with cystic fibrosis, supporting a role for sex hormones in the disease process. Further understanding of the mechanisms that modulate sex hormone receptors in airway disease may serve as future targets for therapy. © 2013 Wiley Periodicals, Inc.

Effects of Puberty on Cystic Fibrosis Related Pulmonary Exacerbations in Women Versus Men

PubMed Central

Sutton, Shelby; Rosenbluth, Daniel; Raghavan, Deepa; Zheng, Jie; Jain, Raksha

2014-01-01

Summary Background Epidemiologic data from studies of airway diseases, such as asthma, chronic obstructive pulmonary disease, and cystic fibrosis indicate a gender disparity where women have worse outcomes. The explanation for this is largely unknown. We hypothesize that female sex hormones play a role in this gender disparity, predisposing women to more exacerbations and decreased lung function post-puberty. Objective In Cystic Fibrosis, to determine if puberty marks a point of increasing exacerbations and decreasing lung function in women relative to men. Methods Using the United States Cystic Fibrosis Foundation Patient Registry, we used linear regression to compare lung function and rate of pulmonary exacerbations in men versus women before and after puberty. Results Of 5,137 subjects who met inclusion criteria, 2,689 were male and 2,448 were female. Average age of puberty was found to be 13.2 ± 2.2 years in men and 11.2 ± 2.0 years of age in women. Percent predicted FEV1 pre-and post-puberty were no different between males versus females (P = 0.44 pre-puberty and P = 0.16 post-puberty). In contrast, women had a significantly higher rate of pulmonary exacerbations post-puberty than men (1.17 ± 1.35 exacerbations per year in women versus 0.95 ± 1.27 in men; P < 0.001) despite controlling for morphometrics, co-morbidities, and microbiologic variables. Conclusion After puberty, the rate of pulmonary exacerbations increased in adolescent women relative to men with cystic fibrosis, supporting a role for sex hormones in the disease process. Further understanding of the mechanisms that modulate sex hormone receptors in airway disease may serve as future targets for therapy. PMID:23460461

MiR-153 inhibits migration and invasion of human non-small-cell lung cancer by targeting ADAM19

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shan, Nianxi; Institute of Medical Sciences, Xiangya Hospital, Central South University, Changsha, Hunan 410008; Shen, Liangfang

Highlights: • Decreased miR-153 and up-regulated ADAM19 are correlated with NSCLC pathology. • MiR-153 inhibits the proliferation and migration and invasion of NSCLC cells in vitro. • ADAM19 is a direct target of miR-153. • ADAM19 is involved in miR-153-suppressed migration and invasion of NSCLC cells. - Abstract: MiR-153 was reported to be dysregulated in some human cancers. However, the function and mechanism of miR-153 in lung cancer cells remains unknown. In this study, we investigated the role of miR-153 in human non-small-cell lung cancer (NSCLC). Using qRT-PCR, we demonstrated that miR-153 was significantly decreased in clinical NSCLC tissues andmore » cell lines, and downregulation of miR-153 was significantly correlated with lymph node status. We further found that ectopic expression of miR-153 significantly inhibited the proliferation and migration and invasion of NSCLC cells in vitro, suggesting that miR-153 may be a novel tumor suppressor in NSCLC. Further integrated analysis revealed that ADAM19 is as a direct and functional target of miR-153. Luciferase reporter assay demonstrated that miR-153 directly targeted 3′UTR of ADAM19, and correlation analysis revealed an inverse correlation between miR-153 and ADAM19 mRNA levels in clinical NSCLC tissues. Knockdown of ADAM19 inhibited migration and invasion of NSCLC cells which was similar with effects of overexpression of miR-153, while overexpression of ADAM19 attenuated the function of miR-153 in NSCLC cells. Taken together, our results highlight the significance of miR-153 and ADAM19 in the development and progression of NSCLC.« less

Recovery from welding-fume-exposure-induced lung fibrosis and pulmonary function changes in sprague dawley rats.

PubMed

Sung, Jae Hyuck; Choi, Byung-Gil; Maeng, Seung-Hee; Kim, Soo-Jin; Chung, Yong Hyun; Han, Jeong Hee; Song, Kyung Seuk; Lee, Yong Hwan; Cho, Yong Bong; Cho, Myung-Haing; Kim, Kwang Jong; Hyun, Jin Suk; Yu, Il Je

2004-12-01

Welder's pneumoconiosis has generally been determined as benign based on the absence of pulmonary function abnormalities in welders with marked radiographic abnormalities. Yet, there have also been several reports on welders with respiratory symptoms, indicating lung function impairment, X-ray abnormalities, and extensive fibrosis. Accordingly, this study attempted to investigate the inflammatory responses and pulmonary function changes in rats during a 60-day welding-fume-inhalation exposure period to elucidate the process of fibrosis. The rats were exposed to manual metal-arc stainless-steel welding fumes (MMA-SS) with total suspended particulate concentrations of 64.8 +/- 0.9 (low dose) and 107.8 +/- 2.6 mg/m3 (high dose) for 2 h per day in an inhalation chamber for 60 days. Animals were sacrificed after the initial 2-h exposure and after 15, 30, and 60 days, and the pulmonary function was also measured every week after the daily exposure. Elevated cellular differential counts were also measured in the acellular bronchoalveolar lavage fluid of the rats exposed to the MMA-SS fumes for 60 days. Among the pulmonary function test parameters, only the tidal volume showed a statistically significant and dose-dependent decrease after 35 to 60 days of MMA-SS welding-fume exposure. When the rats exposed to the welding fumes were left for 60 days to recover their lung function and cellular differentiation, recovery was observed in both the high and low-dose rats exposed up to 30 days, resulting in the disappearance of inflammatory cells and restoration of the tidal volume. The rats exposed for 60 days at the low dose also recovered from the inflammation and tidal volume loss, yet the rats exposed for 60 days at the high dose did not fully recover even after a 60-day recovery period. Therefore, when taken together, the results of the current study suggest that a decrease in the tidal volume could be used as an early indicator of pulmonary fibrosis induced by welding-fume exposure in Sprague Dawley rats, and fibrosis would seem to be preventable if the exposure is short-term and moderate.

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.

Comparison between effects of pressure support and pressure-controlled ventilation on lung and diaphragmatic damage in experimental emphysema.

PubMed

Padilha, Gisele de A; Horta, Lucas F B; Moraes, Lillian; Braga, Cassia L; Oliveira, Milena V; Santos, Cíntia L; Ramos, Isalira P; Morales, Marcelo M; Capelozzi, Vera Luiza; Goldenberg, Regina C S; de Abreu, Marcelo Gama; Pelosi, Paolo; Silva, Pedro L; Rocco, Patricia R M

2016-12-01

In patients with emphysema, invasive mechanical ventilation settings should be adjusted to minimize hyperinflation while reducing respiratory effort and providing adequate gas exchange. We evaluated the impact of pressure-controlled ventilation (PCV) and pressure support ventilation (PSV) on pulmonary and diaphragmatic damage, as well as cardiac function, in experimental emphysema. Emphysema was induced by intratracheal instillation of porcine pancreatic elastase in Wistar rats, once weekly for 4 weeks. Control animals received saline under the same protocol. Eight weeks after first instillation, control and emphysema rats were randomly assigned to PCV (n = 6/each) or PSV (n = 6/each) under protective tidal volume (6 ml/kg) for 4 h. Non-ventilated control and emphysema animals (n = 6/group) were used to characterize the model and for molecular biology analysis. Cardiorespiratory function, lung histology, diaphragm ultrastructure alterations, extracellular matrix organization, diaphragmatic proteolysis, and biological markers associated with pulmonary inflammation, alveolar stretch, and epithelial and endothelial cell damage were assessed. Emphysema animals exhibited cardiorespiratory changes that resemble human emphysema, such as increased areas of lung hyperinflation, pulmonary amphiregulin expression, and diaphragmatic injury. In emphysema animals, PSV compared to PCV yielded: no changes in gas exchange; decreased mean transpulmonary pressure (Pmean,L), ratio between inspiratory and total time (Ti/Ttot), lung hyperinflation, and amphiregulin expression in lung; increased ratio of pulmonary artery acceleration time to pulmonary artery ejection time, suggesting reduced right ventricular afterload; and increased ultrastructural damage to the diaphragm. Amphiregulin correlated with Pmean,L (r = 0.99, p < 0.0001) and hyperinflation (r = 0.70, p = 0.043), whereas Ti/Ttot correlated with hyperinflation (r = 0.81, p = 0.002) and Pmean,L (r = 0.60, p = 0.04). In the model of elastase-induced emphysema used herein, PSV reduced lung damage and improved cardiac function when compared to PCV, but worsened diaphragmatic injury.

Regional Emphysema Score Predicting Overall Survival, Quality of Life, and Pulmonary Function Recovery in Early-Stage Lung Cancer Patients.

PubMed

Dai, Jie; Liu, Ming; Swensen, Stephen J; Stoddard, Shawn M; Wampfler, Jason A; Limper, Andrew H; Jiang, Gening; Yang, Ping

2017-05-01

Pulmonary emphysema is a frequent comorbidity in lung cancer, but its role in tumor prognosis remains obscure. Our aim was to evaluate the impact of the regional emphysema score (RES) on a patient's overall survival, quality of life (QOL), and recovery of pulmonary function in stage I to II lung cancer. Between 1997 and 2009, a total of 1073 patients were identified and divided into two surgical groups-cancer in the emphysematous (group 1 [n = 565]) and nonemphysematous (group 2 [n = 435]) regions-and one nonsurgical group (group 3 [n = 73]). RES was derived from the emphysematous region and categorized as mild (≤5%), moderate (6%-24%), or severe (25%-60%). In group 1, patients with a moderate or severe RES experienced slight decreases in postoperative forced expiratory volume in 1 second, but increases in the ratio of forced expiratory volume in 1 second to forced vital capacity compared with those with a mild RES (p < 0.01); however, this correlation was not observed in group 2. Posttreatment QOL was lower in patients with higher RESs in all groups, mainly owing to dyspnea (p < 0.05). Cox regression analysis revealed that patients with a higher RES had significantly poorer survival in both surgical groups, with adjusted hazard ratios of 1.41 and 1.43 for a moderate RES and 1.63 and 2.04 for a severe RES, respectively; however, this association was insignificant in the nonsurgical group (adjusted hazard ratio of 0.99 for a moderate or severe RES). In surgically treated patients with cancer in the emphysematous region, RES is associated with postoperative changes in lung function. RES is also predictive of posttreatment QOL related to dyspnea in early-stage lung cancer. In both surgical groups, RES is an independent predictor of survival. Copyright © 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Partial pneumonectomy of telomerase null mice carrying shortened telomeres initiates cell growth arrest resulting in a limited compensatory growth response

PubMed Central

Jackson, Sha-Ron; Lee, Jooeun; Reddy, Raghava; Williams, Genevieve N.; Kikuchi, Alexander; Freiberg, Yael; Warburton, David

2011-01-01

Telomerase mutations and significantly shortened chromosomal telomeres have recently been implicated in human lung pathologies. Natural telomere shortening is an inevitable consequence of aging, which is also a risk factor for development of lung disease. However, the impact of shortened telomeres and telomerase dysfunction on the ability of lung cells to respond to significant challenge is still largely unknown. We have previously shown that lungs of late generation, telomerase null B6.Cg-Terctm1Rdp mice feature alveolar simplification and chronic stress signaling at baseline, a phenocopy of aged lung. To determine the role telomerase plays when the lung is challenged, B6.Cg-Terctm1Rdp mice carrying shortened telomeres and wild-type controls were subjected to partial pneumonectomy. We found that telomerase activity was strongly induced in alveolar epithelial type 2 cells (AEC2) of the remaining lung immediately following surgery. Eighty-six percent of wild-type animals survived the procedure and exhibited a burst of early compensatory growth marked by upregulation of proliferation, stress response, and DNA repair pathways in AEC2. In B6.Cg-Terctm1Rdp mice carrying shortened telomeres, response to pneumonectomy was characterized by decreased survival, diminished compensatory lung growth, attenuated distal lung progenitor cell response, persistent DNA damage, and cell growth arrest. Overall, survival correlated strongly with telomere length. We conclude that functional telomerase and properly maintained telomeres play key roles in both long-term survival and the early phase of compensatory lung growth following partial pneumonectomy. PMID:21460122

Biomarkers for Radiation Pneumonitis Using Noninvasive Molecular Imaging.

PubMed

Medhora, Meetha; Haworth, Steven; Liu, Yu; Narayanan, Jayashree; Gao, Feng; Zhao, Ming; Audi, Said; Jacobs, Elizabeth R; Fish, Brian L; Clough, Anne V

2016-08-01

Our goal is to develop minimally invasive biomarkers for predicting radiation-induced lung injury before symptoms develop. Currently, there are no biomarkers that can predict radiation pneumonitis. Radiation damage to the whole lung is a serious risk in nuclear accidents or in radiologic terrorism. Our previous studies have shown that a single dose of 15 Gy of x-rays to the thorax causes severe pneumonitis in rats by 6-8 wk. We have also developed a mitigator for radiation pneumonitis and fibrosis that can be started as late as 5 wk after radiation. We used 2 functional SPECT probes in vivo in irradiated rat lungs. Regional pulmonary perfusion was measured by injection of (99m)Tc-macroaggregated albumin. Perfused volume was determined by comparing the volume of distribution of (99m)Tc-macroaggregated albumin to the anatomic lung volume obtained by small-animal CT. A second probe, (99m)Tc-labeled Duramycin, which binds to apoptotic cells, was used to measure pulmonary cell death in the same rat model. The perfused volume of lung was decreased by about 25% at 1, 2, and 3 wk after receipt of 15 Gy, and (99m)Tc-Duramycin uptake was more than doubled at 2 and 3 wk. There was no change in body weight, breathing rate, or lung histology between irradiated and nonirradiated rats at these times. Pulmonary vascular resistance and vascular permeability measured in isolated perfused lungs ex vivo increased at 2 wk after 15 Gy of irradiation. Our results suggest that SPECT biomarkers have the potential to predict radiation injury to the lungs before substantial functional or histologic damage is observed. Early prediction of radiation pneumonitis in time to initiate mitigation will benefit those exposed to radiation in the context of therapy, accidents, or terrorism. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

miR-130b-3p Modulates Epithelial-Mesenchymal Crosstalk in Lung Fibrosis by Targeting IGF-1.

PubMed

Li, Shuhong; Geng, Jing; Xu, Xuefeng; Huang, Xiaoxi; Leng, Dong; Jiang, Dingyuan; Liang, Jiurong; Wang, Chen; Jiang, Dianhua; Dai, Huaping

2016-01-01

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and usually lethal fibrotic lung disease with largely unknown etiology and pathogenesis. Evidence suggests microRNAs (miRNA) contribute to pathogenesis of IPF. In this study, we sought to identify miRNA expression signatures and determine the role of miR-130b-3p in lung fibrosis. The miRNA expression profile of the lungs from patients with IPF and normal donors was determined by Affymetrix microarray, and transcriptome with Affymetrix array. The functions and signal pathways as well as miRNA-mRNA networks were established by bioinformatics analysis. Luciferase assays and ELISA were used to confirm the miRNA target gene. The effect of miRNA-transfected epithelium on fibroblast activities was assessed using a co-culture system. The fibroblast activities were determined by qRT-PCR, western blotting, Transwell and BrdU assays. Seven miRNAs were significantly decreased in IPF lungs, with miR-130b-3p being the highest in the miRNA-mRNA network. Insulin-like growth factor (IGF-1) was a target gene of miR-130b-3p in the epithelium. miR-130b-3p inhibition in the epithelium induced collagen I expression and enhanced the proliferation and migration ability of fibroblast in co-culture systems, which mimicked the functions of exogenous IGF-1 on fibroblasts. Neutralizing IGF-1 with an antibody significantly reduced the modulatory effects of miR-130b-3p inhibitor-transfected epithelium on the activation of fibroblasts. Our results show that miR-130b-3p was downregulated in IPF lungs. miR-130b-3p downregulation contributed to the activation of fibroblasts and the dysregulated epithelial-mesenchymal crosstalk by promoting IGF-1 secretion from lung epithelium, suggesting a key regulatory role for this miRNA in preventing lung fibrosis.

Lack of species-specific difference in pulmonary function when using mouse versus human plasma in a mouse model of hemorrhagic shock.

PubMed

Peng, Zhanglong; Pati, Shibani; Fontaine, Magali J; Hall, Kelly; Herrera, Anthony V; Kozar, Rosemary A

2016-11-01

Clinical studies have demonstrated that the early and empiric use of plasma improves survival after hemorrhagic shock. We have demonstrated in rodent models of hemorrhagic shock that resuscitation with plasma is protective to the lungs compared with lactated Ringer's solution. As our long-term objective is to determine the molecular mechanisms that modulate plasma's protective effects in injured bleeding patients, we have used human plasma in a mouse model of hemorrhagic shock. The goal of the current experiments is to determine if there are significant adverse effects on lung injury when using human versus mouse plasma in an established murine model of hemorrhagic shock and laparotomy. Mice underwent laparotomy and 90 minutes of hemorrhagic shock to a mean arterial pressure (MAP) of 35 ± 5 mm Hg followed by resuscitation at 1× shed blood using either mouse fresh frozen plasma (FFP), human FFP, or human lyophilized plasma. Mean arterial pressure was recorded during shock and for the first 30 minutes of resuscitation. After 3 hours, animals were killed, and lungs collected for analysis. There was a significant increase in early MAP when mouse FFP was used to resuscitate animals compared with human FFP or human lyophilized plasma. However, despite these differences, analysis of the mouse lungs revealed no significant differences in pulmonary histopathology, lung permeability, or lung edema between all three plasma groups. Analysis of neutrophil infiltration in the lungs revealed that mouse FFP decreased neutrophil influx as measured by neutrophil staining; however, myeloperoxidase immunostaining revealed no significant differences in between groups. The study of human plasma in a mouse model of hemorrhagic shock is feasible but does reveal some differences compared with mouse plasma-based resuscitation in physiologic measures such as MAP postresuscitation. Measures of end organ function such as lung injury appear to be comparable in this acute model of hemorrhagic shock and resuscitation.

Variation in Cilia Protein Genes and Progression of Lung Disease in Cystic Fibrosis.

PubMed

Blue, Elizabeth; Louie, Tin L; Chong, Jessica X; Hebbring, Scott J; Barnes, Kathleen C; Rafaels, Nicholas M; Knowles, Michael R; Gibson, Ronald L; Bamshad, Michael J; Emond, Mary J

2018-04-01

Cystic fibrosis, like primary ciliary dyskinesia, is an autosomal recessive disorder characterized by abnormal mucociliary clearance and obstructive lung disease. We hypothesized that genes underlying the development or function of cilia may modify lung disease severity in persons with cystic fibrosis. To test this hypothesis, we compared variants in 93 candidate genes in both upper and lower tertiles of lung function in a large cohort of children and adults with cystic fibrosis with those of a population control dataset. Variants within candidate genes were tested for association using the SKAT-O test, comparing cystic fibrosis cases defined by poor (n = 127) or preserved (n = 127) lung function with population controls (n = 3,269 or 3,148, respectively). Associated variants were then tested for association with related phenotypes in independent datasets. Variants in DNAH14 and DNAAF3 were associated with poor lung function in cystic fibrosis, whereas variants in DNAH14 and DNAH6 were associated with preserved lung function in cystic fibrosis. Associations between DNAH14 and lung function were replicated in disease-related phenotypes characterized by obstructive lung disease in adults. Genetic variants within DNAH6, DNAH14, and DNAAF3 are associated with variation in lung function among persons with cystic fibrosis.

Simvastatin attenuates stroke-induced splenic atrophy and lung susceptibility to spontaneous bacterial infection in mice

PubMed Central

Jin, Rong; Zhu, Xiaolei; Liu, Lin; Nanda, Anil; Granger, D Neil; Li, Guohong

2013-01-01

Background and Purpose Statins are widely used in the primary and secondary prevention of ischemic stroke, but their effects on stroke-induced immunodeppression and post-stroke infections are elusive. We investigated effects of simvastatin treatment on stroke-induced splenic atrophy and lung susceptibility to bacterial infection in acute experimental stroke in mice. Methods Ischemic stroke was induced by transient occlusion of middle cerebral artery (MCAO) followed by reperfusion. In some experiments, splenectomies were performed 2 weeks prior to MCAO. Animals were randomly assigned to sham and MCAO groups treated subcutaneously with vehicle or simvastatin (20 mg/kg/day). Brain infarction, neurological function, brain interferon-γ expression, splenic atrophy and apoptosis, and lung infection were examined. Results Simvastatin reduced stroke-induced spleen atrophy and splenic apoptosis via increased mitochrondrial anti-apoptotic Bcl-2 expression and decreased pro-apoptotic Bax translocation from cytosol into mitochondria. Splenectomy reduced brain interferon-γ (3d) and infarct size (5d) after stroke and these effects were reversed by adoptive transfer of splenocytes. Simvastatin inhibited brain interferon-γ (3d) and reduced infarct volume and neurological deficits (5d) after stroke, and these protective effects were observed not only in naïve stroke mice but also in splenectomied stroke mice adoptively transferred with splenocytes. Simvastatin also decreased the stroke-associated lung susceptibility to spontaneous bacterial infection. Conclusions Results provide the first direct experimental evidence that simvastatin ameliorates stroke-induced peripheral immunodepression by attenuating spleen atrophy and lung bacterial infection. These findings contribute to a better understanding of beneficial effects of statins in the treatment of stroke. PMID:23391769

Budesonide inhalation ameliorates endotoxin-induced lung injury in rabbits

PubMed Central

Gao, Wei

2015-01-01

Acute respiratory distress syndrome (ARDS) is a serious clinical problem that has a 30–50% mortality rate. Budesonide has been used to reduce lung injury. This study aims to investigate the effects of nebulized budesonide on endotoxin-induced ARDS in a rabbit model. Twenty-four rabbits were randomized into three groups. Rabbits in the control and budesonide groups were injected with endotoxin. Thereafter, budesonide or saline was instilled, ventilated for four hours, and recovered spontaneous respiratory. Peak pressure, compliance, and PaO2/FiO2 were monitored for 4 h. After seven days, PaO2/FiO2 ratios were measured. Wet-to-dry weight ratios, total protein, neutrophil elastase, white blood cells, and percentage of neutrophils in BALF were evaluated. TNF-α, IL-1β, IL-8, and IL-10 in BALF were detected. Lung histopathologic injury and seven-day survival rate of the three groups were recorded. Peak pressure was downregulated, but compliance and PaO2/FiO2 were upregulated by budesonide. PaO2/FiO2 ratios significantly increased due to budesonide. Wet-to-dry weight ratios, total protein, neutrophil elastase, white blood cells and percentage of neutrophils in BALF decreased in the budesonide group. TNF-α, IL-1β, and IL-8 levels decreased in BALF, while IL-10 levels increased in the budesonide group. Lung injuries were reduced and survival rate was upregulated by budesonide. Budesonide effectively ameliorated respiratory function, attenuated endotoxin-induced lung injury, and improved the seven-day survival rate. PMID:25956681

Budesonide inhalation ameliorates endotoxin-induced lung injury in rabbits.

PubMed

Gao, Wei; Ju, Nanying

2015-12-01

Acute respiratory distress syndrome (ARDS) is a serious clinical problem that has a 30-50% mortality rate. Budesonide has been used to reduce lung injury. This study aims to investigate the effects of nebulized budesonide on endotoxin-induced ARDS in a rabbit model. Twenty-four rabbits were randomized into three groups. Rabbits in the control and budesonide groups were injected with endotoxin. Thereafter, budesonide or saline was instilled, ventilated for four hours, and recovered spontaneous respiratory. Peak pressure, compliance, and PaO2/FiO2 were monitored for 4 h. After seven days, PaO2/FiO2 ratios were measured. Wet-to-dry weight ratios, total protein, neutrophil elastase, white blood cells, and percentage of neutrophils in BALF were evaluated. TNF-α, IL-1β, IL-8, and IL-10 in BALF were detected. Lung histopathologic injury and seven-day survival rate of the three groups were recorded. Peak pressure was downregulated, but compliance and PaO2/FiO2 were upregulated by budesonide. PaO2/FiO2 ratios significantly increased due to budesonide. Wet-to-dry weight ratios, total protein, neutrophil elastase, white blood cells and percentage of neutrophils in BALF decreased in the budesonide group. TNF-α, IL-1β, and IL-8 levels decreased in BALF, while IL-10 levels increased in the budesonide group. Lung injuries were reduced and survival rate was upregulated by budesonide. Budesonide effectively ameliorated respiratory function, attenuated endotoxin-induced lung injury, and improved the seven-day survival rate. © 2015 by the Society for Experimental Biology and Medicine.

Schistosoma mansoni infection causes oxidative stress and alters receptor for advanced glycation endproduct (RAGE) and tau levels in multiple organs in mice.

PubMed

de Oliveira, Ramatis Birnfeld; Senger, Mario Roberto; Vasques, Laura Milan; Gasparotto, Juciano; dos Santos, João Paulo Almeida; Pasquali, Matheus Augusto de Bittencourt; Moreira, José Claudio Fonseca; Silva, Floriano Paes; Gelain, Daniel Pens

2013-04-01

Schistosomiasis is a parasitic disease caused by trematode worms from the Schistosoma genus and is characterized by high rates of morbidity. The main organs affected in this pathology, such as liver, kidneys and spleen, are shifted to a pro-oxidant state in the course of the infection. Here, we compared oxidative stress parameters of liver, kidney and spleen with other organs affected by schistosomiasis - heart, brain cortex and lungs. The results demonstrated that mice infected with Schistosoma mansoni had altered non-enzymatic antioxidant status in lungs and brain, increased carbonyl levels in lungs, and a moderate level of oxidative stress in heart. A severe redox imbalance in liver and kidneys and decreased non-enzymatic antioxidant capacity in spleen were also observed. Superoxide dismutase and catalase activities were differently modulated in liver, kidney and heart, and we found that differences in Superoxide dismutase 2 and catalase protein content may be responsible for these differences. Lungs had decreased receptor for advanced glycation endproduct expression and the brain cortex presented altered tau expression and phosphorylation levels, suggesting important molecular changes in these tissues, as homeostasis of these proteins is widely associated with the normal function of their respective organs. We believe that these results demonstrate for the first time that changes in the redox profile and expression of tissue-specific proteins of organs such as heart, lungs and brain are observed in early stages of S. mansoni infection. Copyright © 2013 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

Conservation of small-airway function by tacrolimus/cyclosporine conversion in the management of bronchiolitis obliterans following lung transplantation.

PubMed

Revell, M P; Lewis, M E; Llewellyn-Jones, C G; Wilson, I C; Bonser, R S

2000-12-01

We studied serial lung function in 11 patients with bronchiolitis obliterans syndrome who were treated with tacrolimus conversion following lung or heart-lung transplantation. Our results show that tacrolimus conversion slows the decline of lung function in bronchiolitis obliterans syndrome. The attenuation continues for at least 1 year following conversion.