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Sample records for airway assessment factors

  1. Trefoil factor-2 reverses airway remodeling changes in allergic airways disease.

    PubMed

    Royce, Simon G; Lim, Clarice; Muljadi, Ruth C; Samuel, Chrishan S; Ververis, Katherine; Karagiannis, Tom C; Giraud, Andrew S; Tang, Mimi L K

    2013-01-01

    Trefoil factor 2 (TFF2) is a small peptide with an important role in mucosal repair. TFF2 is up-regulated in asthma, suggesting a role in asthma pathogenesis. Given its known biological role in promoting epithelial repair, TFF2 might be expected to exert a protective function in limiting the progression of airway remodeling in asthma. The contribution of TFF2 to airway remodeling in asthma was investigated by examining the expression of TFF2 in the airway and lung, and evaluating the effects of recombinant TFF2 treatment on established airway remodeling in a murine model of chronic allergic airways disease (AAD). BALB/c mice were sensitized and challenged with ovalbumin (OVA) or saline for 9 weeks, whereas mice with established OVA-induced AAD were treated with TFF2 or vehicle control (intranasally for 14 d). Effects on airway remodeling, airway inflammation, and airway hyperresponsiveness were then assessed, whereas TFF2 expression was determined by immunohistochemistry. TFF2 expression was significantly increased in the airways of mice with AAD, compared with expression levels in control mice. TFF2 treatment resulted in reduced epithelial thickening, subepithelial collagen deposition, goblet-cell metaplasia, bronchial epithelium apoptosis, and airway hyperresponsiveness (all P < 0.05, versus vehicle control), but TFF2 treatment did not influence airway inflammation. The increased expression of endogenous TFF2 in response to chronic allergic inflammation is insufficient to prevent the progression of airway inflammation and remodeling in a murine model of chronic AAD. However, exogenous TFF2 treatment is effective in reversing aspects of established airway remodeling. TFF2 has potential as a novel treatment for airway remodeling in asthma. PMID:22652198

  2. Methods of airway resistance assessment.

    PubMed

    Urbankowski, Tomasz; Przybyłowski, Tadeusz

    2016-01-01

    Airway resistance is the ratio of driving pressure to the rate of the airflow in the airways. The most frequent methods used to measure airway resistance are whole-body plethysmography, the interrupter technique and the forced oscillation technique. All these methods allow to measure resistance during respiration at the level close to tidal volume, they do not require forced breathing manoeuvres or deep breathing during measurement. The most popular method for measuring airway resistance is whole-body plethysmography. The results of plethysmography include among others the following parameters: airway resistance (Raw), airway conductance (Gaw), specific airway resistance (sRaw) and specific airway conductance (sGaw). The interrupter technique is based on the assumption that at the moment of airway occlusion, air pressure in the mouth is equal to the alveolar pressure . In the forced oscillation technique (FOT), airway resistance is calculated basing on the changes in pressure and flow caused by air vibration. The methods for measurement of airway resistance that are described in the present paper seem to be a useful alternative to the most common lung function test - spirometry. The target group in which these methods may be widely used are particularly the patients who are unable to perform spirometry. PMID:27238174

  3. Airway Assessment for Office Sedation/Anesthesia.

    PubMed

    Rosenberg, Morton B; Phero, James C

    2015-01-01

    Whenever a patient is about to receive sedation or general anesthesia, no matter what the technique, the preoperative assessment of the airway is one of the most important steps in ensuring patient safety and positive outcomes. This article, Part III in the series on airway management, is directed at the ambulatory office practice and focuses on predicting the success of advanced airway rescue techniques. PMID:26061578

  4. Cephalometric Assessment of Upper Airway Effects on Craniofacial Morphology.

    PubMed

    Ardehali, Mojtaba Mohamadi; Zarch, Varasteh Vakili; Joibari, Mohammad-Esmaeil; Kouhi, Ali

    2016-03-01

    To investigate craniofacial growth deformities in children with upper airway obstruction, this controlled study was performed. Cephalometry is used as a screening test for anatomic abnormalities in patients with obstructive sleep apnea syndrome. Therefore, the current work selected this method to investigate the effect of upper airway obstruction on craniofacial morphology.Patients with upper airway obstruction (104) were compared with 71 controls. Patients with upper airway compromise had mandibular hypoplasia, mandibular retrognathism, and higher hard palates in comparison with controls with no history of airway obstruction. The difference was higher in the older age group.Airway obstruction has significant correlation craniofacial morphology. Our findings support the idea of early assessment and thorough management of mouth breathing in children. PMID:26967073

  5. The use of Google Glass for airway assessment and management.

    PubMed

    Spencer, Rebecca J; Chang, Philip H; Guimaraes, Alexander R; Firth, Paul G

    2014-09-01

    Currently, information about airway assessment and tracheal intubation is communicated verbally or in writing. Google Glass can record this information in real time with minimal disruption to work flow, using standard operating room lighting. PMID:25039494

  6. Delivered dose estimate to standardize airway hyperresponsiveness assessment in mice.

    PubMed

    Robichaud, Annette; Fereydoonzad, Liah; Schuessler, Thomas F

    2015-04-15

    Airway hyperresponsiveness often constitutes a primary outcome in respiratory studies in mice. The procedure commonly employs aerosolized challenges, and results are typically reported in terms of bronchoconstrictor concentrations loaded into the nebulizer. Yet, because protocols frequently differ across studies, especially in terms of aerosol generation and delivery, direct study comparisons are difficult. We hypothesized that protocol variations could lead to differences in aerosol delivery efficiency and, consequently, in the dose delivered to the subject, as well as in the response. Thirteen nebulization patterns containing common protocol variations (nebulization time, duty cycle, particle size spectrum, air humidity, and/or ventilation profile) and using increasing concentrations of methacholine and broadband forced oscillations (flexiVent, SCIREQ, Montreal, Qc, Canada) were created, characterized, and studied in anesthetized naïve A/J mice. A delivered dose estimate calculated from nebulizer-, ventilator-, and subject-specific characteristics was introduced and used to account for protocol variations. Results showed that nebulization protocol variations significantly affected the fraction of aerosol reaching the subject site and the delivered dose, as well as methacholine reactivity and sensitivity in mice. From the protocol variants studied, addition of a slow deep ventilation profile during nebulization was identified as a key factor for optimization of the technique. The study also highlighted sensitivity differences within the lung, as well as the possibility that airway responses could be selectively enhanced by adequate control of nebulizer and ventilator settings. Reporting results in terms of delivered doses represents an important standardizing element for assessment of airway hyperresponsiveness in mice. PMID:25637610

  7. Techniques of assessing small airways dysfunction

    PubMed Central

    McNulty, William; Usmani, Omar S.

    2014-01-01

    The small airways are defined as those less than 2 mm in diameter. They are a major site of pathology in many lung diseases, not least chronic obstructive pulmonary disease (COPD) and asthma. The small airways are frequently involved early in the course of these diseases, with significant pathology demonstrable often before the onset of symptoms or changes in spirometry and imaging. Despite their importance, they have proven relatively difficult to study. This is in part due to their relative inaccessibility to biopsy and their small size which makes their imaging difficult. Traditional lung function tests may only become abnormal once there is a significant burden of disease within them. This has led to the term ‘the quiet zone’ of the lung. In recent years, more specialised tests have been developed which may detect these changes earlier, perhaps offering the possibility of earlier diagnosis and intervention. These tests are now moving from the realms of clinical research laboratories into routine clinical practice and are increasingly useful in the diagnosis and monitoring of respiratory diseases. This article gives an overview of small airways physiology and some of the routine and more advanced tests of airway function. PMID:26557240

  8. Epidermal growth factor system regulates mucin production in airways

    PubMed Central

    Takeyama, Kiyoshi; Dabbagh, Karim; Lee, Heung-Man; Agustí, Carlos; Lausier, James A.; Ueki, Iris F.; Grattan, Kathleen M.; Nadel, Jay A.

    1999-01-01

    Goblet-cell hyperplasia is a critical pathological feature in hypersecretory diseases of airways. However, the underlying mechanisms are unknown, and no effective therapy exists. Here we show that stimulation of epidermal growth factor receptors (EGF-R) by its ligands, EGF and transforming growth factor α (TGFα), causes MUC5AC expression in airway epithelial cells both in in vitro and in vivo. We found that a MUC5AC-inducing epithelial cell line, NCI-H292, expresses EGF-R constitutively; EGF-R gene expression was stimulated further by tumor necrosis factor α (TNFα). EGF-R ligands increased the expression of MUC5AC at both gene and protein levels, and this effect was potentiated by TNFα. Selective EGF-R tyrosine kinase inhibitors blocked MUC5AC expression induced by EGF-R ligands. Pathogen-free rats expressed little EGF-R protein in airway epithelial cells; intratracheal instillation of TNFα induced EGF-R in airway epithelial cells, and subsequent instillation of EGF-R ligands increased the number of goblet cells, Alcian blue–periodic acid–Schiff staining (reflecting mucous glycoconjugates), and MUC5AC gene expression, whereas TNFα, EGF, or TGFα alone was without effect. In sensitized rats, three intratracheal instillations of ovalbumin resulted in EGF-R expression and goblet-cell production in airway epithelium. Pretreatment with EGF-R tyrosine kinase inhibitor, BIBX1522, prevented goblet-cell production both in rats stimulated by TNFα-EGF-R ligands and in an asthma model. These findings suggest potential roles for inhibitors of the EGF-R cascade in hypersecretory diseases of airways. PMID:10077640

  9. Tissue factor pathway inhibitor prevents airway obstruction, respiratory failure and death due to sulfur mustard analog inhalation

    SciTech Connect

    Rancourt, Raymond C. Veress, Livia A. Ahmad, Aftab Hendry-Hofer, Tara B. Rioux, Jacqueline S. Garlick, Rhonda B. White, Carl W.

    2013-10-01

    Sulfur mustard (SM) inhalation causes airway injury, with enhanced vascular permeability, coagulation, and airway obstruction. The objective of this study was to determine whether recombinant tissue factor pathway inhibitor (TFPI) could inhibit this pathogenic sequence. Methods: Rats were exposed to the SM analog 2-chloroethyl ethyl sulfide (CEES) via nose-only aerosol inhalation. One hour later, TFPI (1.5 mg/kg) in vehicle, or vehicle alone, was instilled into the trachea. Arterial O{sub 2} saturation was monitored using pulse oximetry. Twelve hours after exposure, animals were euthanized and bronchoalveolar lavage fluid (BALF) and plasma were analyzed for prothrombin, thrombin–antithrombin complex (TAT), active plasminogen activator inhibitor-1 (PAI-1) levels, and fluid fibrinolytic capacity. Lung steady-state PAI-1 mRNA was measured by RT-PCR analysis. Airway-capillary leak was estimated by BALF protein and IgM, and by pleural fluid measurement. In additional animals, airway cast formation was assessed by microdissection and immunohistochemical detection of airway fibrin. Results: Airway obstruction in the form of fibrin-containing casts was evident in central conducting airways of rats receiving CEES. TFPI decreased cast formation, and limited severe hypoxemia. Findings of reduced prothrombin consumption, and lower TAT complexes in BALF, demonstrated that TFPI acted to limit thrombin activation in airways. TFPI, however, did not appreciably affect CEES-induced airway protein leak, PAI-1 mRNA induction, or inhibition of the fibrinolytic activity present in airway surface liquid. Conclusions: Intratracheal administration of TFPI limits airway obstruction, improves gas exchange, and prevents mortality in rats with sulfur mustard-analog-induced acute lung injury. - Highlights: • TFPI administration to rats after mustard inhalation reduces airway cast formation. • Inhibition of thrombin activation is the likely mechanism for limiting casts. • Rats given TFPI

  10. Tissue factor pathway inhibitor prevents airway obstruction, respiratory failure and death due to sulfur mustard analog inhalation

    PubMed Central

    Rancourt, Raymond C.; Veress, Livia A.; Ahmad, Aftab; Hendry-Hofer, Tara B.; Rioux, Jacqueline S.; Garlick, Rhonda B.; White, Carl W.

    2013-01-01

    Sulfur mustard (SM) inhalation causes airway injury, with enhanced vascular permeability, coagulation, and airway obstruction. The objective of this study was to determine whether recombinant tissue factor pathway inhibitor (TFPI) could inhibit this pathogenic sequence. Methods Rats were exposed to the SM analog 2-chloroethyl ethyl sulfide (CEES) via nose-only aerosol inhalation. One hour later, TFPI (1.5 mg/kg) in vehicle, or vehicle alone, were instilled into the trachea. Arterial O2 saturation was monitored using pulse oximetry. Twelve hours after exposure, animals were euthanized and bronchoalveolar lavage fluid (BALF) and plasma analyzed for prothrombin, thrombin-antithrombin complex (TAT), active plasminogen activator inhibitor-1 (PAI-1) levels, and fluid fibrinolytic capacity. Lung steady-state PAI-1 mRNA was measured by RT-PCR analysis. Airway-capillary leak was estimated by BALF protein and IgM, and by pleural fluid measurement. In additional animals, airway cast formation was assessed by microdissection and immunohistochemical detection of airway fibrin. Results Airway obstruction in the form of fibrin-containing casts were evident in central conducting airways of rats receiving CEES. TFPI decreased cast formation, and limited severe hypoxemia. Findings of reduced prothrombin consumption, and lower TAT complexes in BALF, demonstrated that TFPI acted to limit thrombin activation in airways. TFPI, however, did not appreciably affect CEES-induced airway protein leak, PAI-1 mRNA induction, or inhibition of the fibrinolytic activity present in airway surface liquid. Conclusions Intratracheal administration of TFPI limits airway obstruction, improves gas exchange, and prevents mortality in rats with sulfur mustard-analog-induced acute lung injury. PMID:23727623

  11. Risk assessment of pre-hospital trauma airway management by anaesthesiologists using the predictive Bayesian approach

    PubMed Central

    2010-01-01

    Introduction Endotracheal intubation (ETI) has been considered an essential part of pre-hospital advanced life support. Pre-hospital ETI, however, is a complex intervention also for airway specialist like anaesthesiologists working as pre-hospital emergency physicians. We therefore wanted to investigate the quality of pre-hospital airway management by anaesthesiologists in severely traumatised patients and identify possible areas for improvement. Method We performed a risk assessment according to the predictive Bayesian approach, in a typical anaesthesiologist-manned Norwegian helicopter emergency medical service (HEMS). The main focus of the risk assessment was the event where a patient arrives in the emergency department without ETI despite a pre-hospital indication for it. Results In the risk assessment, we assigned a high probability (29%) for the event assessed, that a patient arrives without ETI despite a pre-hospital indication. However, several uncertainty factors in the risk assessment were identified related to data quality, indications for use of ETI, patient outcome and need for special training of ETI providers. Conclusion Our risk assessment indicated a high probability for trauma patients with an indication for pre-hospital ETI not receiving it in the studied HEMS. The uncertainty factors identified in the assessment should be further investigated to better understand the problem assessed and consequences for the patients. Better quality of pre-hospital airway management data could contribute to a reduction of these uncertainties. PMID:20409306

  12. Airway Count and Emphysema Assessed by Chest CT Imaging Predicts Clinical Outcome in Smokers

    PubMed Central

    Valim, Clarissa; Yamashiro, Tsuneo; Estépar, Raúl San José; Ross, James C.; Matsuoka, Shin; Bartholmai, Brian; Hatabu, Hiroto; Silverman, Edwin K.; Washko, George R.

    2010-01-01

    Background: Recently, it has been shown that emphysematous destruction of the lung is associated with a decrease in the total number of terminal bronchioles. It is unknown whether a similar decrease is visible in the more proximal airways. We aimed to assess the relationships between proximal airway count, CT imaging measures of emphysema, and clinical prognostic factors in smokers, and to determine whether airway count predicts the BMI, airflow obstruction, dyspnea, and exercise capacity (BODE) index. Methods: In 50 smokers, emphysema was measured on CT scans and airway branches from the third to eighth generations of the right upper lobe apical bronchus were counted manually. The sum of airway branches from the sixth to eighth generations represented the total airway count (TAC). For each subject, the BODE index was determined. We used logistic regression to assess the ability of TAC to predict a high BODE index (≥ 7 points). Results: TAC was inversely associated with emphysema (r = −0.54, P < .0001). TAC correlated with the modified Medical Research Council dyspnea score (r = −0.42, P = .004), FEV1% predicted (r = 0.52, P = .0003), 6-min walk distance (r = 0.36, P = .012), and BODE index (r = −0.55, P < .0001). The C-statistics, which correspond to the area under the receiver operating characteristic curve, for the ability of TAC alone and TAC, emphysema, and age to predict a high BODE index were 0.84 and 0.92, respectively. Conclusions: TAC is lower in subjects with greater emphysematous destruction and is a predictor of a high BODE index. These results suggest that CT imaging-based TAC may be a unique COPD-related phenotype in smokers. PMID:20558554

  13. Sex Steroids Influence Brain-Derived Neurotropic Factor Secretion From Human Airway Smooth Muscle Cells.

    PubMed

    Wang, Sheng-Yu; Freeman, Michelle R; Sathish, Venkatachalem; Thompson, Michael A; Pabelick, Christina M; Prakash, Y S

    2016-07-01

    Brain derived neurotropic factor (BDNF) is emerging as an important player in airway inflammation, remodeling, and hyperreactivity. Separately, there is increasing evidence that sex hormones contribute to pathophysiology in the lung. BDNF and sex steroid signaling are thought to be intricately linked in the brain. There is currently little information on BDNF and sex steroid interactions in the airway but is relevant to understanding growth factor signaling in the context of asthma in men versus women. In this study, we assessed the effect of sex steroids on BDNF expression and secretion in human airway smooth muscle (ASM). Human ASM was treated with estrogen (E2 ) or testosterone (T, 10 nM each) and intracellular BDNF and secreted BDNF measured. E2 and T significantly reduced secretion of BDNF; effects prevented by estrogen and androgen receptor inhibitor, ICI 182,780 (1 μM), and flutamide (10 μM), respectively. Interestingly, no significant changes were observed in intracellular BDNF mRNA or protein expression. High affinity BDNF receptor, TrkB, was not altered by E2 or T. E2 (but not T) significantly increased intracellular cyclic AMP levels. Notably, Epac1 and Epac2 expression were significantly reduced by E2 and T. Furthermore, SNARE complex protein SNAP25 was decreased. Overall, these novel data suggest that physiologically relevant concentrations of E2 or T inhibit BDNF secretion in human ASM, suggesting a potential interaction of sex steroids with BDNF in the airway that is different from brain. The relevance of sex steroid-BDNF interactions may lie in their overall contribution to airway diseases such as asthma. J. Cell. Physiol. 231: 1586-1592, 2016. © 2015 Wiley Periodicals, Inc. PMID:26566264

  14. Lung clearance index in the assessment of airways disease.

    PubMed

    Horsley, Alex

    2009-06-01

    In the last few years there has been a growing interest in lung clearance index (LCI), a measure of lung physiology derived from multiple breath washout tests. This resurgence of interest was initially driven by the recognition that such assessments were capable of detecting early airways disease in children, and are more sensitive and easier to perform in this population than conventional lung function tests [Aurora P, Kozlowska W, Stocks J. Gas mixing efficiency from birth to adulthood measured by multiple-breath washout. Respir Physiol Neurobiol, 2005;148(1-2):125-39]. With an appreciation of the importance of earlier identification of airways dysfunction, and prevention of irreversible structural airway changes, methods of following airways disease in these "silent years" are especially important. LCI has now been reported in studies involving all age groups, from infants to adults [Lum S, Gustafsson P, Ljungberg H, Hulskamp G, Bush A, Carr SB, et al. Early detection of cystic fibrosis lung disease: multiple-breath washout versus raised volume tests. Thorax, 2007;62(4):341-7; Horsley AR, Gustafsson PM, Macleod K, Saunders CJ, Greening AP, Porteous D, et al. Lung clearance index is a sensitive, repeatable and practical measure of airways disease in adults with cystic fibrosis. Thorax, 2008;63:135-40], and has a narrow range of normal over this wide age range, making it especially suitable for long-term follow-up studies. In cystic fibrosis (CF) particularly, there is a pressing need for sensitive and repeatable clinical endpoints for therapeutic interventions [Rosenfeld M. An overview of endpoints for cystic fibrosis clinical trials: one size does not fit all. Proc Am Thorac Soc, 2007;4(4):299-301], and LCI has been proposed as an outcome measure in future CF gene therapy studies [Davies JC, Cunningham S, Alton EW, Innes JA. Lung clearance index in CF: a sensitive marker of lung disease severity. Thorax, 2008;63(2):96-7]. This review will consider how LCI is

  15. Preoperative airway assessment - experience gained from a multicentre cluster randomised trial and the Danish Anaesthesia Database.

    PubMed

    Nørskov, Anders Kehlet

    2016-05-01

    Difficulties with airway management in relation to general anaesthesia have been a challenge for the anaesthesiologist since the birth of anaesthesia. Massive landmark improvements have been made and general anaesthesia is now regarded as a safe procedure. However, rare, difficult airway management still occurs and it prompts increased risk of morbidity and mortality - especially when not anticipated. Several preoperative risk factors for airway difficulties have been identified, yet none have convincing diagnostic accuracy as stand alone tests. Combining several risk factors increase the predictive value of the test and multivariable risk models have been developed. The Simplified Airway Risk Index (SARI) is a predictive model developed for anticipation of a difficult direct laryngoscopy. However, neither the diagnostic accuracy of the SARI nor of any other model has been tested prospectively and compared with existing practice for airway assessment in a randomised trial setting. The first objective of this thesis was to quantify the proportion of unanticipated difficult intubation and difficult mask ventilation in Denmark. The second objective was to design a cluster randomised trial, using state of the art methodology, in order to test the clinical impact of using the SARI for preoperative airway assessment compared with a clinical judgement based on usual practice for airway assessment. Finally, to test if implementation of the SARI would reduce the proportion of unanticipated difficult intubation compared with usual care for airway assessment. This thesis is based on data from the Danish Anaesthesia Database (DAD). Paper 1 presents an observational cohort study on 188,064 patients who underwent tracheal intubation from 2008 to 2011. Data on the anaesthesiologists' preoperative anticipations of airway difficulties was compared with actual airway management conditions, thus enabling an estimation of the proportion of unanticipated difficulties with intubation

  16. Evaluation of Airway Reactivity and Immune Characteristics as Risk Factors for Wheezing Early in Life

    PubMed Central

    Yao, Weiguo; Barbé-Tuana, Florencia M.; Llapur, Conrado J.; Jones, Marcus H.; Tiller, Christina; Kimmel, Risa; Kisling, Jeffrey; Nguyen, Evelyn T.; Nguyen, James; Yu, Zhangsheng; Kaplan, Mark H.; Tepper, Robert S.

    2010-01-01

    Background Childhood asthma is most often characterized by recurrent wheezing, airway hyper-reactivity, and atopy; however, our understanding of these relationships from early in life remains unclear. Respiratory illnesses and atopic sensitization early in life may produce an interaction between innate and acquired immune responses leading to airway inflammation and heightened airway reactivity. Objective We hypothesized that pre-morbid airway reactivity and immunologic characteristics of infants without prior episodes of wheezing would be associated with subsequent wheezing during 1-year follow-up. Methods 116 infants with chronic dermatitis were enrolled prior to episodes of wheezing. Airway reactivity, allergen-specific IgE, cytokine production by stimulated peripheral blood mononuclear cells (PBMCs), and percentages of dendritic cells were measured upon entry and airway reactivity was reassessed at 1-year follow-up. Linear regression models were used to evaluate predictor’s effect on continuous outcomes. Results milk and/or egg sensitization was associated with heightened airway reactivity prior to wheezing and after the onset of wheezing; however, these factors were not associated with an increased risk of wheezing. There was an interaction between initial airway reactivity and wheezing as a determinant of airway reactivity at follow-up. In addition, cytokine production by stimulated PBMCs was a risk factor for wheezing, while increased percentages of conventional dendritic cells were protective for wheezing. Conclusion Our data in a selected cohort of infants support a model with multiple risk factors for subsequent wheezing that are independent of initial airway reactivity; however, the etiologic factors that produce wheezing very early in life may contribute to heightened airway reactivity. PMID:20816184

  17. Assessment of Airway Microbiota and Inflammation in Cystic Fibrosis Using Multiple Sampling Methods

    PubMed Central

    Wagner, Brandie D.; Robertson, Charles E.; Stevens, Mark J.; Szefler, Stanley J.; Accurso, Frank J.; Sagel, Scott D.; Harris, J. Kirk

    2015-01-01

    Rationale: Oropharyngeal (OP) swabs and induced sputum (IS) are used for airway bacteria surveillance in nonexpectorating children with cystic fibrosis (CF). Molecular analyses of these airway samples detect complex microbial communities. However, the optimal noninvasive sampling approach for microbiota analyses and the clinical relevance of microbiota, particularly its relationship to airway inflammation, is not well characterized. Objectives: The goals of this study were to compare molecular analyses of concurrently collected saliva, OP swabs, IS, and expectorated sputum (ES) from children with CF and to determine the association between microbiota, lung function, and airway inflammation. Methods: Saliva, OP swabs, IS, and ES were collected from 16 children with CF. Spirometry was performed. Measurements and Main Results: Respiratory and saliva samples (n = 61) were sequenced for bacterial microbial communities, and total and CF-specific bacterial quantitative PCR assays were performed. Airway samples underwent conventional culture for CF-specific pathogens. Neutrophil elastase, IL-1β, IL-1ra, IL-6, Il-8, TNF-α, and vascular endothelial growth factor were measured in ES and IS. Sequencing results from individual subjects were similar across samples, with greater between-subject than within-subject variation. However, Pseudomonas and Staphylococcus were detected in higher relative abundance from lower airways (ES and IS) compared with paired upper airway samples (OP and saliva). Pseudomonas, Staphylococcus, and Enterobacteriaceae correlated with increased airway inflammation. Divergence between microbiota in upper airway compared with lower airway samples, indicating greater differences between communities, was associated with increased sputum neutrophil elastase. Conclusions: Bacteria detected in IS samples resemble ES samples, whereas OP samples may underrepresent bacteria associated with airway inflammation. Divergence of lower airway communities from

  18. Role of Insulin-like Growth Factor Binding Protein-3 in Allergic Airway Remodeling

    PubMed Central

    Veraldi, Kristen L.; Gibson, Bethany T.; Yasuoka, Hidekata; Myerburg, Michael M.; Kelly, Elizabeth A.; Balzar, Silvana; Jarjour, Nizar N.; Pilewski, Joseph M.; Wenzel, Sally E.; Feghali-Bostwick, Carol A.

    2009-01-01

    Rationale: The hallmarks of allergic asthma are airway inflammation, obstruction, and remodeling. Airway remodeling may lead to irreversible airflow obstruction with increased morbidity and mortality. Despite advances in the treatment of asthma, the mechanisms underlying airway remodeling are still poorly understood. We reported that insulin-like growth factor (IGF) binding proteins (IGFBPs) contribute to extracellular matrix deposition in idiopathic pulmonary fibrosis; however, their contribution to airway remodeling in asthma has not been established. Objectives: We hypothesized that IGFBP-3 is overexpressed in asthma and contributes to airway remodeling. Methods: We evaluated levels of IGFBP-3 in tissues and bronchoalveolar lavage fluid from patients with asthma at baseline and 48 hours after allergen challenge, in reparative epithelium in an in vitro wounding assay, and in conditioned media from cytokine- and growth factor–stimulated primary epithelial cells. Measurements and Main Results: IGFBP-3 levels and distribution were evaluated by Western blot, ELISA, and immunofluorescence. IGFBP-3 is increased in vivo in the airway epithelium of patients with asthma compared with normal control subjects. The concentration of IGFBP-3 is increased in the bronchoalveolar lavage fluid of patients with asthma after allergen challenge, its levels are increased in reparative epithelium in an in vitro wounding assay and in the conditioned medium of primary airway epithelial cell cultures stimulated with IGF-I. Conclusions: Our results suggest that one mechanism of allergic airway remodeling is through the secretion of the profibrotic IGFBP-3 from IGF-I–stimulated airway epithelial cells during allergic inflammation. PMID:19608721

  19. Synergistic and additive killing by antimicrobial factors found in human airway surface liquid.

    PubMed

    Singh, P K; Tack, B F; McCray, P B; Welsh, M J

    2000-11-01

    Airway surface liquid contains multiple factors thought to provide a first line of defense against bacteria deposited in the airways. Although the antimicrobial action of individual factors has been studied, less is known about how they work in combination. We examined the combined action of six antimicrobial peptides found in airway surface liquid. The paired combinations of lysozyme-lactoferrin, lysozyme-secretory leukocyte protease inhibitor (SLPI), and lactoferrin-SLPI were synergistic. The triple combination of lysozyme, lactoferrin, and SLPI showed even greater synergy. Other combinations involving the human beta-defensins, LL-37, and tobramycin (often administered to cystic fibrosis patients by inhalation) were additive. Because the airway surface liquid salt concentration may be elevated in cystic fibrosis patients, we examined the effect of salt on the synergistic combinations. As the ionic strength increased, synergistic interactions were lost. Our data suggest that the antibacterial potency of airway surface liquid may be significantly increased by synergistic and additive interactions between antimicrobial factors. These results also suggest that increased salt concentrations that may exist in cystic fibrosis could inhibit airway defenses by diminishing these synergistic interactions. PMID:11053013

  20. Assessment of major airway obstruction using image analysis of digital CT information

    NASA Astrophysics Data System (ADS)

    McLennan, Geoffrey; Shamsolkottabi, Susanne; Hoffman, Eric A.

    1996-04-01

    Major airway obstruction (trachea, right and left main bronchi) is an important cause of morbidity and mortality. Management requires adequate assessment of the position, extent and severity of the obstructing or stenotic segment. The objective of this study was to evaluate 3D reconstruction of the major airways using volumetric image display and analysis (VIDA), in subjects with major airflow obstruction. We have evaluated five subjects with major airway obstruction using Electron Beam Computed Tomography (EBCT) with a contiguous 3 mm slice thickness at total lung capacity. The digital information was transferred to a Sun Workstation (SPARC 5) for data analysis using VIDA. From this data set, the airway dimensions were calculated using a method for airway centerline determination and slice reformatting so as to section the airway perpendicular to its local long axis. Once appropriately sectioned, a number of different methods were used in edge finding. The airways were also presented as a surface rendered 3D image in either still or movie format. Finally, all subjects underwent flexible bronchoscopy to assess the abnormalities by direct visualization, with results of the bronchoscopic assessment being compared to the VIDA measurements. In all subjects, the volumetric image display and analysis gave anatomically correct and detailed images, which could be accurately measured. This information enabled appropriate pre-planning of operative corrective procedures, that included laser therapy, stent placement and balloon bronchoplasty. We conclude that the volumetric image display and analysis provides useful and reliable information for the management of major airflow obstruction.

  1. Candida spp. airway colonization: A potential risk factor for Acinetobacter baumannii ventilator-associated pneumonia.

    PubMed

    Tan, Xiaojiang; Zhu, Song; Yan, Dongxing; Chen, Weiping; Chen, Ruilan; Zou, Jian; Yan, Jingdong; Zhang, Xiangdong; Farmakiotis, Dimitrios; Mylonakis, Eleftherios

    2016-08-01

    This retrospective study was conducted to identify potential risk factors for Acinetobacter baumannii (A. baumannii) ventilator-associated pneumonia (VAP) and evaluate the association between Candida spp. airway colonization and A. baumannii VAP. Intensive care unit (ICU) patients who were on mechanical ventilation (MV) for ≥48 hours were divided into the following groups: patients with and without Candida spp. airway colonization; colonized patients receiving antifungal treatment or not; patients with A. baumannii VAP and those without VAP. Logistic regression analysis and propensity score matching were used to identify factors independently associated with A. baumannii VAP. Among 618 eligible patients, 264 (43%) had Candida spp. airway colonization and 114 (18%) developed A. baumannii VAP. Along with MV for ≥7 days (adjusted odds ratio [aOR] 8.9, 95% confidence intervals [95% CI] 4.9-15.8) and presence of a central venous catheter (aOR 3.2, 95% CI 1.1-9), Candida spp. airway colonization (aOR 2.6, 95% CI 1.6-4.3) was identified as an independent risk factor for A. baumannii VAP. Patients with Candida spp. airway colonization were more likely to develop A. baumannii VAP than non-colonized patients (23% vs 15%, P=.01 and 34% vs. 15%, P<.001 in propensity score-matched subgroups). Administration of antifungal agents was not associated with A. baumannii VAP (29% vs. 21%, P=.153) but with higher in-hospital mortality (53% vs. 39%, P=.037). Candida spp. airway colonization (43%) and A. baumannii VAP (18%) were common in ICU patients who were on mechanical ventilation for at least 48 hours. Candida spp. airway colonization was an independent risk factor for subsequent A. baumannii VAP. PMID:27001670

  2. Assessment of Airway Bronchodilation by Spirometry Compared to Airway Obstruction in Young Children with Asthma

    PubMed Central

    Vilozni, Daphna; Livnat, Galit; Bar-Yoseph, Ronen

    2016-01-01

    A reversibility test by an increase of greater than 12% in FEV1 can support a diagnosis of asthma and alter a patient's treatment plan but may not be applicable to the young ages. We retrospectively gathered spirometric data from 85/271 asthmatic children having mild obstruction (FEV1 > 80% predicted), age 2.6–6.9 years. Spirometry was performed before and 20 min after inhalation of 200 mcg Albuterol. We defined a deviation below −1.64 z scores from control as obstruction and an increased above 1.64 scores from control as a positive response to bronchodilators. Sensitivity of the index was considered significant if it captured >68% of the participants. The sensitivity of detecting airway obstruction in these children by FEV1 was 15.3% and 62.4% by FEF25–75. A positive response to Albuterol was an increase of 9.2% for FEV1 (12% for adults) and 18.5% for FEF25–75. The sensitivity for detecting a response to Albuterol in mild asthma was 64.7% by FEV1 and 91.8% by FEF25–75. Young children having normal spirometry can demonstrate airway reversibility. The response of spirometry parameters to bronchodilators may be more sensitive than obstruction detection and may help to support the diagnosis of asthma and adjust treatment plan. PMID:27445548

  3. Intracellular insulin-like growth factor-1 induces Bcl-2 expression in airway epithelial cells.

    PubMed

    Chand, Hitendra S; Harris, Jennifer Foster; Mebratu, Yohannes; Chen, Yangde; Wright, Paul S; Randell, Scott H; Tesfaigzi, Yohannes

    2012-05-01

    Bcl-2, a prosurvival protein, regulates programmed cell death during development and repair processes, and it can be oncogenic when cell proliferation is deregulated. The present study investigated what factors modulate Bcl-2 expression in airway epithelial cells and identified the pathways involved. Microarray analysis of mRNA from airway epithelial cells captured by laser microdissection showed that increased expression of IL-1β and insulin-like growth factor-1 (IGF-1) coincided with induced Bcl-2 expression compared with controls. Treatment of cultured airway epithelial cells with IL-1β and IGF-1 induced Bcl-2 expression by increasing Bcl-2 mRNA stability with no discernible changes in promoter activity. Silencing the IGF-1 expression using short hairpin RNA showed that intracellular IGF-1 (IC-IGF-1) was increasing Bcl-2 expression. Blocking epidermal growth factor receptor or IGF-1R activation also suppressed IC-IGF-1 and abolished the Bcl-2 induction. Induced expression and colocalization of IC-IGF-1 and Bcl-2 were observed in airway epithelial cells of mice exposed to LPS or cigarette smoke and of patients with cystic fibrosis and chronic bronchitis but not in the respective controls. These studies demonstrate that IC-IGF-1 induces Bcl-2 expression in epithelial cells via IGF-1R and epidermal growth factor receptor pathways, and targeting IC-IGF-1 could be beneficial to treat chronic airway diseases. PMID:22461702

  4. Assessing mucus and airway morphology in response to a segmental allergen challenge using OCT (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Adams, David C.; Miller, Alyssa J.; Holz, Jasmin A.; Szabari, Margit V.; Hariri, Lida P.; Harris, R. Scott; Cho, Jocelyn L.; Hamilos, Daniel L.; Luster, Andrew D.; Medoff, Benjamin D.; Suter, Melissa J.

    2016-03-01

    Asthma affects hundreds of millions of people worldwide, and the prevalence of the disease appears to be increasing. One of the most important aspects of asthma is the excessive bronchoconstriction that results in many of the symptoms experienced by asthma sufferers, but the relationship between bronchoconstriction and airway morphology is not clearly established. We present the imaging results of a study involving a segmental allergen challenge given to both allergic asthmatic (n = 12) and allergic non-asthmatic (n = 19) human volunteers. Using OCT, we have imaged and assessed baseline morphology in a right upper lobe (RUL) airway, serving as the control, and a right middle lobe (RML) airway, in which the allergen was to be administered. After a period of 24 hours had elapsed following the administration of the allergen, both airways were again imaged and the response morphology assessed. A number of airway parameters were measured and compared, including epithelial thickness, mucosal thickness and buckling, lumen area, and mucus content. We found that at baseline epithelial thickness, mucosal thickness, and mucosal buckling were greater in AAs than ANAs. We also observed statistically significant increases in these values 24 hours after the allergen had been administered for both the ANA and AA sets. In comparison, the control airway which received a diluent showed no statistically significant change.

  5. Temporal and Spatial Expression of Transforming Growth Factor-β after Airway Remodeling to Tobacco Smoke in Rats.

    PubMed

    Hoang, Laura L; Nguyen, Yen P; Aspeé, Rayza; Bolton, Sarah J; Shen, Yi-Hsin; Wang, Lei; Kenyon, Nicholas J; Smiley-Jewell, Suzette; Pinkerton, Kent E

    2016-06-01

    Airway remodeling is strongly correlated with the progression of chronic obstructive pulmonary disease (COPD). In this study, our goal was to characterize progressive structural changes in site-specific airways, along with the temporal and spatial expression of transforming growth factor (TGF)-β in the lungs of male spontaneously hypertensive rats exposed to tobacco smoke (TS). Our studies demonstrated that TS-induced changes of the airways is dependent on airway generation and exposure duration for proximal, midlevel, and distal airways. Stratified squamous epithelial cell metaplasia was evident in the most proximal airways after 4 and 12 weeks but with minimal levels of TGF-β-positive epithelial cells after only 4 weeks of exposure. In contrast, epithelial cells in midlevel and distal airways were strongly TGF-β positive at both 4 and 12 weeks of TS exposure. Airway smooth muscle volume increased significantly at 4 and 12 weeks in midlevel airways. Immunohistochemistry of TGF-β was also found to be significantly increased at 4 and 12 weeks in lymphoid tissues and alveolar macrophages. ELISA of whole-lung homogenate demonstrated that TGF-β2 was increased after 4 and 12 weeks of TS exposure, whereas TGF-β1 was decreased at 12 weeks of TS exposure. Airway levels of messenger RNA for TGF-β2, as well as platelet-derived growth factor-A, granulocyte-macrophage colony-stimulating factor, and vascular endothelial growth factor-α, growth factors regulated by TGF-β, were significantly decreased in animals after 12 weeks of TS exposure. Our data indicate that TS increases TGF-β in epithelial and inflammatory cells in connection with airway remodeling, although the specific role of each TGF-β isoform remains to be defined in TS-induced airway injury and disease. PMID:26637070

  6. Risk assessment of sleeping disorder breathing based on upper airway centerline evaluation

    NASA Astrophysics Data System (ADS)

    Alsufyani, Noura; Shen, Rui; Cheng, Irene; Major, Paul

    2013-02-01

    One of the most important breathing disorders in childhood is obstructive sleep apnea syndrome which affects 2-3% of children, and the reported failure rate of surgical treatment was as high as 54%. A possible reason in respiratory complications is having reduced dimensions of the upper airway which are further compressed when muscle tone is decreased during sleep. In this study, we use Cone-beam computed tomography (CBCT) to assess the location or cause of the airway obstruction. To date, all studies analyzing the upper airway in subjects with Sleeping Disorder Breathing were based on linear, area, or volumetric measurements, which are global computations and can easily ignore local significance. Skeletonization was initially introduced as a 3D modeling technique by which representative medial points of a model are extracted to generate centerlines for evaluations. Although centerlines have been commonly used in guiding surgical procedures, our novelty lies in comparing its geometric properties before and after surgeries. We apply 3D data refinement, registration and projection steps to quantify and localize the geometric deviation in target airway regions. Through cross validation with corresponding subjects' therapy data, we expect to quantify the tolerance threshold beyond which reduced dimensions of the upper airway are not clinically significant. The ultimate goal is to utilize this threshold to identify patients at risk of complications. Outcome from this research will also help establish a predictive model for training and to estimate treatment success based on airway measurements prior to intervention. Preliminary results demonstrate the feasibility of our approach.

  7. Bronchoscopic assessment of airway retention time of aerosolized xylitol

    PubMed Central

    Durairaj, Lakshmi; Neelakantan, Srividya; Launspach, Janice; Watt, Janet L; Allaman, Margaret M; Kearney, William R; Veng-Pedersen, Peter; Zabner, Joseph

    2006-01-01

    Background Human airway surface liquid (ASL) has abundant antimicrobial peptides whose potency increases as the salt concentration decreases. Xylitol is a 5-carbon sugar that has the ability to lower ASL salt concentration, potentially enhancing innate immunity. Xylitol was detected for 8 hours in the ASL after application in airway epithelium in vitro. We tested the airway retention time of aerosolized iso-osmotic xylitol in healthy volunteers. Methods After a screening spirometry, volunteers received 10 ml of nebulized 5% xylitol. Bronchoscopy was done at 20 minutes (n = 6), 90 minutes (n = 6), and 3 hours (n = 5) after nebulization and ASL was collected using microsampling probes, followed by bronchoalveolar lavage (BAL). Xylitol concentration was measured by nuclear magnetic resonance spectroscopy and corrected for dilution using urea concentration. Results All subjects tolerated nebulization and bronchoscopy well. Mean ASL volume recovered from the probes was 49 ± 23 μl. The mean ASL xylitol concentration at 20, 90, and 180 minutes was 1.6 ± 1.9 μg/μl, 0.6 ± 0.6 μg/μl, and 0.1 ± 0.1 μg/μl, respectively. Corresponding BAL concentration corrected for dilution was consistently lower at all time points. The terminal half-life of aerosolized xylitol obtained by the probes was 45 minutes with a mean residence time of 65 minutes in ASL. Corresponding BAL values were 36 and 50 minutes, respectively. Conclusion After a single dose nebulization, xylitol was detected in ASL for 3 hours, which was shorter than our in vitro measurement. The microsampling probe performed superior to BAL when sampling bronchial ASL. PMID:16483382

  8. Involvement of Toll-like receptor 2 and epidermal growth factor receptor signaling in epithelial expression of airway remodeling factors.

    PubMed

    Homma, Tetsuya; Kato, Atsushi; Sakashita, Masafumi; Norton, James E; Suh, Lydia A; Carter, Roderick G; Schleimer, Robert P

    2015-04-01

    Staphylococcus aureus (SA) colonization and infection is common, and may promote allergic or inflammatory airway diseases, such as asthma, cystic fibrosis, and chronic rhinosinusitis by interacting with airway epithelial cells. Airway epithelial cells not only comprise a physical barrier, but also play key roles in immune, inflammatory, repair, and remodeling responses upon encounters with pathogens. To elucidate the impact of SA on epithelial-mediated remodeling of allergic airways, we tested the hypothesis that SA can enhance the remodeling process. Normal human bronchial epithelial (NHBE) cells were stimulated with heat-killed SA (HKSA) or transforming growth factor (TGF) α. Cell extracts were collected to measure mRNA (real-time RT-PCR) and signaling molecules (Western blot); supernatants were collected to measure protein (ELISA) after 24 hours of stimulation. Epidermal growth factor receptor (EGFR) signaling inhibition experiments were performed using a specific EGFR kinase inhibitor (AG1478) and TGF-α was blocked with an anti-TGF-α antibody. HKSA induced both mRNA and protein for TGF-α and matrix metalloproteinase (MMP) 1 from NHBE cells by a Toll-like receptor 2-dependent mechanism. Recombinant human TGF-α also induced mRNA and protein for MMP-1 from NHBE cells; anti-TGF-α antibody inhibited HKSA-induced MMP-1, suggesting that endogenous TGF-α mediates the MMP-1 induction by HKSA. HKSA-induced MMP-1 expression was suppressed when a specific EGFR kinase inhibitor was added, suggesting that EGFR signaling was mediating the HKSA-induced MMP-1 release. Exposure or colonization by SA in the airway may enhance the remodeling of tissue through a TGF-α-dependent induction of MMP-1 expression, and may thereby promote remodeling in airway diseases in which SA is implicated, such as asthma and chronic rhinosinusitis. PMID:25180535

  9. Involvement of Toll-Like Receptor 2 and Epidermal Growth Factor Receptor Signaling in Epithelial Expression of Airway Remodeling Factors

    PubMed Central

    Kato, Atsushi; Sakashita, Masafumi; Norton, James E.; Suh, Lydia A.; Carter, Roderick G.; Schleimer, Robert P.

    2015-01-01

    Staphylococcus aureus (SA) colonization and infection is common, and may promote allergic or inflammatory airway diseases, such as asthma, cystic fibrosis, and chronic rhinosinusitis by interacting with airway epithelial cells. Airway epithelial cells not only comprise a physical barrier, but also play key roles in immune, inflammatory, repair, and remodeling responses upon encounters with pathogens. To elucidate the impact of SA on epithelial-mediated remodeling of allergic airways, we tested the hypothesis that SA can enhance the remodeling process. Normal human bronchial epithelial (NHBE) cells were stimulated with heat-killed SA (HKSA) or transforming growth factor (TGF) α. Cell extracts were collected to measure mRNA (real-time RT-PCR) and signaling molecules (Western blot); supernatants were collected to measure protein (ELISA) after 24 hours of stimulation. Epidermal growth factor receptor (EGFR) signaling inhibition experiments were performed using a specific EGFR kinase inhibitor (AG1478) and TGF-α was blocked with an anti–TGF-α antibody. HKSA induced both mRNA and protein for TGF-α and matrix metalloproteinase (MMP) 1 from NHBE cells by a Toll-like receptor 2–dependent mechanism. Recombinant human TGF-α also induced mRNA and protein for MMP-1 from NHBE cells; anti–TGF-α antibody inhibited HKSA-induced MMP-1, suggesting that endogenous TGF-α mediates the MMP-1 induction by HKSA. HKSA-induced MMP-1 expression was suppressed when a specific EGFR kinase inhibitor was added, suggesting that EGFR signaling was mediating the HKSA-induced MMP-1 release. Exposure or colonization by SA in the airway may enhance the remodeling of tissue through a TGF-α–dependent induction of MMP-1 expression, and may thereby promote remodeling in airway diseases in which SA is implicated, such as asthma and chronic rhinosinusitis. PMID:25180535

  10. Airway assessment based on a three column model of direct laryngoscopy.

    PubMed

    Greenland, K B

    2010-01-01

    Airway assessment has remained a problematic area, largely due to the low sensitivities, specificities and/or positive predictive values of most bedside tests. In this paper a structured overview of the common preoperative airway assessment tests is presented, based on a model for direct laryngoscopy that has been previously described. This model is composed of three columns: anterior middle and posterior The anterior column tests are classified into the assessment of volume and compliance of the submandibular space, the range of movement of the temporomandibular joints and the flexibility of the stylohyoid ligament. Reductions in volume of the anterior column may be absolute or relative. An absolute reduction may occur with shortening of either the incisor-hyoid distance, the temporomandibular joint-incisor distance or the temporomandibular joint-temporomandibular joint distance. A relative reduction may be seen with either prominent upper front incisors or large tongues. Testing of the middle column includes a history and physical examination of the upper respiratory system, imaging of the airway (such as X-ray, computed tomography scans and/or magnetic resonance imaging scans) and nasopharyngoscopy. The posterior column may be assessed by the range of movement of the neck, especially the range of extension of the occipito-atlanto-axial complex. By integrating common tests of the anterior middle and posterior columns within this three-column model, the practitioner may be better positioned to understand the complexity of direct laryngoscopy in both normal and difficult airway scenarios. PMID:20191771

  11. Dendritic cell-derived tumor necrosis factor α modifies airway epithelial cell responses.

    PubMed

    Lutfi, R; Ledford, J R; Zhou, P; Lewkowich, I P; Page, K

    2012-01-01

    Mucosal dendritic cells (DC) are intimately associated with the airway epithelium and thus are ideally situated to be first responders to pathogens. We hypothesize that DC drive innate immune responses through early release of tumor necrosis factor (TNF) α, which drives airway epithelial cell responses. In a mouse model, TNFα release was significantly increased following a single exposure to German cockroach (GC) frass, an event independent of neutrophil recruitment into the airways. While lung epithelial cells and alveolar macrophages failed to release TNFα following GC frass exposure, bone marrow-derived DC (BMDC) produced substantial amounts of TNFα suggesting their importance as early responding cells. This was confirmed by flow cytometry of pulmonary myeloid DC. Addition of GC frass-pulsed BMDC or conditioned media from GC frass-pulsed BMDC to primary mouse tracheal epithelial cells (MTEC) or MLE-15 cells induced chemokine (C-C) motif ligand (CCL) 20 and granulocyte macrophage (GM) colony-stimulating factor (CSF), both of which are important for DC recruitment, survival and differentiation. Importantly, DC do not produce CCL20 or GM-CSF following allergen exposure. Blocking TNFα receptor 1 (TNFR1) completely abolished chemokine production, suggesting that BMDC-derived TNFα induced airway epithelial cell activation and enhancement of the innate immune response. Lastly, blocking TNFR1 in vivo resulted in significantly decreased CCL20 and GM-CSF production in the lungs of mice. Together, our data strongly suggest that DC-derived TNFα plays a crucial role in the initiation of innate immune responses through the modification of airway epithelial cell responses. PMID:22517116

  12. Airway shape assessment with visual feed-back in asthma and obstructive diseases

    NASA Astrophysics Data System (ADS)

    Fetita, Catalin; Ortner, Margarete; Brillet, Pierre-Yves; Ould Hmeidi, Yahya; Pr"teux, Françoise

    2010-02-01

    Airway remodeling in asthma patients has been studied in vivo by means of endobronchial biopsies allowing to assess structural and inflammatory changes. However, this technique remains relatively invasive and difficult to use in longitudinal trials. The development of alternative non-invasive tests, namely exploiting high-resolution imaging modalities such as MSCT, is gaining interest in the medical community. This paper develops a fullyautomated airway shape assessment approach based on the 3D segmentation of the airway lumen from MSCT data. The objective is to easily notify the radiologist on bronchus shape variations (stenoses, bronchiectasis) along the airway tree during a simple visual investigation. The visual feed-back is provided by means of a volumerendered color coding of the airway calibers which are robustly defined and computed, based on a specific 3D discrete distance function able to deal with small size structures. The color volume rendering (CVR) information is further on reinforced by the definition and computation of a shape variation index along the airway medial axis enabling to detect specific configurations of stenoses. Such cases often occur near bifurcations (bronchial spurs) and they are either missed in the CVR or difficult to spot due to occlusions by other segments. Consequently, all detected shape variations (stenoses, dilations and thickened spurs) can be additionally displayed on the medial axis and investigated together with the CVR information. The proposed approach was evaluated on a MSCT database including twelve patients with severe or moderate persistent asthma, or severe COPD, by analyzing segmental and subsegmental bronchi of the right lung. The only CVR information provided for a limited number of views allowed to detect 78% of stenoses and bronchial spurs in these patients, whereas the inclusion of the shape variation index enabled to complement the missing information.

  13. Assessment of Risk in Chronic Airways Disease Evaluation (ARCADE): Protocol and preliminary data.

    PubMed

    Gale, Nichola S; Albarrati, Ali M; Munnery, Margaret M; Munnery, Iain C; Irfan, Mujammil; Bolton, Charlotte E; Rambaran, Curtis N; Singer, Ruth M Tal; Cockcroft, John R; Shale, Dennis J

    2014-11-01

    Chronic obstructive pulmonary disease (COPD) is a multisystem disease. Established comorbidities include cardiovascular disease, osteoporosis, loss of muscle mass and function, depression, and impaired quality of life. The natural history is not well understood. The Assessment of Risk in Chronic Airways Disease Evaluation (ARCADE) is a longitudinal study of comorbidities in COPD. The primary aims are to delineate the progression and interrelationships of cardiovascular disease and associated comorbidities. Each year ARCADE aims to recruit 250 patients diagnosed with COPD and 50 comparators (free from respiratory disease). Assessments include spirometry, body composition, blood pressure, aortic stiffness (pulse wave velocity (PWV)), noninvasive measures of cardiac output, systemic inflammatory mediators, blood and urine biochemistry, and physical and health outcomes. These will be repeated at 2 and 5 years. In the first year of recruitment, 350 patients and 100 comparators were recruited. The reproducibility of aortic PWV, cardiac output, stroke volume, and cardiac index was evaluated and accepted in 30 patients free from overt cardiovascular disease. The preliminary data from ARCADE have demonstrated acceptable reproducibility of hemodynamic outcome measures. Further longitudinal data collection will increase knowledge of the progression and interactions between cardiovascular risk factors and other comorbidities in COPD. PMID:25159833

  14. Impact of Continuous Positive Airway Pressure on Cardiovascular Risk Factors in High-Risk Patients.

    PubMed

    Zhao, Ying Y; Redline, Susan

    2015-11-01

    Cardiovascular disease remains the leading cause of morbidity and mortality in developed countries. Obstructive sleep apnea is a highly prevalent condition characterized by repetitive upper airway collapse during sleep. A large body of evidence suggests that obstructive sleep apnea is associated with the development of cardiovascular disease and increased cardiovascular morbidity and mortality. Continuous positive airway pressure (CPAP) is the current gold standard for the treatment of obstructive sleep apnea. CPAP devices maintain upper airway patency using a pneumatic splint, thereby ameliorating the repetitive deoxygenation and reoxygenation characteristic of sleep in obstructive sleep apnea patients. Accumulating evidence suggests that CPAP treatment may lead to a reduction in blood pressure. Limited evidence also suggests that CPAP therapy may modulate glucose metabolism, serum cholesterol levels, and inflammatory biomarkers. Thus, CPAP treatment may be associated with cardiovascular risk factor modification in patients with obstructive sleep apnea, who are often obese and at an increased risk of developing cardiovascular disease. This review updates the knowledge on the effects of CPAP on cardiovascular risk factors from recently published randomized trials. PMID:26370408

  15. Keratinocyte growth factor accelerates wound closure in airway epithelium during cyclic mechanical strain.

    PubMed

    Waters, C M; Savla, U

    1999-12-01

    The airway epithelium may be damaged by inhalation of noxious agents, in response to pathogens, or during endotracheal intubation and mechanical ventilation. Maintenance of an intact epithelium is important for lung fluid balance, and the loss of epithelium may stimulate inflammatory responses. Epithelial repair in the airways following injury must occur on a substrate that undergoes cyclic elongation and compression during respiration. We have previously shown that cyclic mechanical strain inhibits wound closure in the airway epithelium (Savla and Waters, 1998b). In this study, we investigated the stimulation of epithelial wound closure by keratinocyte growth factor (KGF) in vitro and the mechanisms by which KGF overcomes the inhibition due to mechanical strain. Primary cultures of normal human bronchial epithelial cells (NHBE) and a cell line of human airway epithelial cells, Calu 3, were grown on Silastic membranes, and a wound was scraped across the well. The wells were then exposed to cyclic strain using the Flexercell Strain Unit, and wound closure was measured. While cyclic elongation (20% maximum) and cyclic compression (approximately 2%) both inhibited wound closure in untreated wells, treatment with KGF (50 ng/ml) significantly accelerated wound closure and overcame the inhibition due to cyclic strain. Since wound closure involves cell spreading, migration, and proliferation, we investigated the effect of cyclic strain on cell area, cell-cell distance, and cell velocity at the wound edge. While the cell area increased in unstretched monolayers, the cell area of monolayers in compressed regions decreased significantly. Treatment with KGF increased the cell area in both cyclically elongated and compressed cells. Also, when cells were treated with KGF, cell velocity was significantly increased in both static and cyclically strained monolayers, and cyclic strain did not inhibit cell migration. These results suggest that KGF is an important factor in

  16. Myeloid Differentiation Factor 88–Dependent Signaling Is Critical for Acute Organic Dust–Induced Airway Inflammation in Mice

    PubMed Central

    Bauer, Christopher; Kielian, Tammy; Wyatt, Todd A.; Romberger, Debra J.; West, William W.; Gleason, Angela M.

    2013-01-01

    Organic dust exposure within agricultural environments results in airway diseases. Toll-like receptor 2 (TLR2) and TLR4 only partly account for the innate response to these complex dust exposures. To determine the central pathway in mediating complex organic dust–induced airway inflammation, this study targeted the common adaptor protein, myeloid differentiation factor 88 (MyD88), and investigated the relative contributions of receptors upstream from this adaptor. Wild-type, MyD88, TLR9, TLR4, IL-1 receptor I (RI), and IL-18R knockout (KO) mice were challenged intranasally with organic dust extract (ODE) or saline, according to an established protocol. Airway hyperresponsiveness (AHR) was assessed by invasive pulmonary measurements. Bronchoalveolar lavage fluid was collected to quantitate leukocyte influx and cytokine/chemokine (TNF-α, IL-6, chemokine [C-X-C motif] ligands [CXCL1 and CXCL2]) concentrations. Lung tissue was collected for histopathology. Lung cell apoptosis was determined by a terminal deoxynucleotidyl transferase dUTP nick-end labeling assay, and lymphocyte influx and intercellular adhesion molecule–1 (ICAM-1) expression were assessed by immunohistochemistry. ODE-induced AHR was significantly attenuated in MyD88 KO mice, and neutrophil influx and cytokine/chemokine production were nearly absent in MyD88 KO animals after ODE challenges. Despite a near-absent airspace inflammatory response, lung parenchymal inflammation was increased in MyD88 KO mice after repeated ODE exposures. ODE-induced epithelial-cell ICAM-1 expression was diminished in MyD88 KO mice. No difference was evident in the small degree of ODE-induced lung-cell apoptosis. Mice deficient in TLR9, TLR4, and IL-18R, but not IL-1IR, demonstrated partial protection against ODE-induced neutrophil influx and cytokine/chemokine production. Collectively, the acute organic dust–induced airway inflammatory response is highly dependent on MyD88 signaling, and is dictated, in part, by

  17. Pediatric cardiac catheterization procedure with dexmedetomidine sedation: Radiographic airway patency assessment

    PubMed Central

    Thimmarayappa, Ashwini; Chandrasekaran, Nivash; Jagadeesh, A. M.; Joshi, Shreedhar S.

    2015-01-01

    Aims: The aim of the study was to measure airway patency objectively during dexmedetomidine sedation under radiographic guidance in spontaneously breathing pediatric patients scheduled for cardiac catheterization procedures. Subjects and Methods: Thirty-five patients in the age group 5–10 years scheduled for cardiac catheterization procedures were enrolled. All study patients were given loading dose of dexmedetomidine at 1 μg/kg/min for 10 min and then maintenance dose of 1.5 μg/kg/h. Radiographic airway patency was assessed at the start of infusion (0 min) and after 30 min. Antero-posterior (AP) diameters were measured manually at the nasopharyngeal and retroglossal levels. Dynamic change in airway between inspiration and expiration was considered a measure of airway collapsibility. Patients were monitored for hemodynamics, recovery time and complications. Statistical Analysis: Student paired t-test was used for data analysis. P < 0.05 was considered significant. Results: Minimum and maximum AP diameters were compared at 0 and 30 min. Nasopharyngeal level showed significant reduction in the minimum (6.27 ± 1.09 vs. 4.26 ± 1.03, P < 0.0001) and maximum (6.51 ± 1.14 vs. 5.99 ± 1.03, P < 0.0001) diameters. Similarly retroglossal level showed significant reduction in the minimum (6.98 ± 1.09 vs. 5.27 ± 1.15, P < 0.0001) and maximum (7.49 ± 1.22 vs. 6.92 ± 1.12, P < 0.0003) diameters. The degree of collapsibility was greater at 30 min than baseline (P < 0.0001). There was a significant decrease in heart rate (P < 0.0001), and the average recovery time was 39.86 ± 12.22 min. Conclusion: Even though airway patency was maintained in all children sedated with dexmedetomidine, there were significant reductions in the upper airway dimensions measured, so all precautions to manage the airway failure should be taken. PMID:25566708

  18. Assessment of Airway Resistance in Normal Trained and Fat Untrained Adolescent Boys Influenced by Exercise Experiences

    PubMed Central

    Ghanbarzadeh, Mohsen; Habibi, Abdolhamid; Shakeriyan, Said

    2013-01-01

    Background Overweight and obese children are at increased risk of a wide range of health conditions including respiratory diseases. In addition, inactivity can decrease pulmonary function. This study assessed the effect of obesity and inactivity on pulmonary function impairment in adolescents. Materials and Methods This study was conducted on 80 adolescents. Subjects were divided into two groups. Group I included 40 untrained (VO2max= 29.30±4.20) fat adolescents (UO). Group II included 40 healthy trained (VO2max= 58.11±2.23) normal weight adolescents (TN). Body mass index (BMI), body fat percentage and waist to hip ratio (WHR) were calculated and pulmonary function tests were carried out according to the standard protocols. Data were analyzed using student's “t” test and Pearson's correlation coefficient. Results UO had significantly lower pulmonary function values than the TN group. They also showed lower FEV1/FVC ratio when compared to TN group (P < 0.05). In UO group, BMI, body fat percentage and WHR had a significant negative correlation with pulmonary function whereas in TN group only BMI had significant negative correlation with pulmonary function. A significant decrease in FEV1 was observed in the two groups, which led to a decrease in FEV1/FVC% after the exercise compared to before. Thus, exercise test induced airway resistance in both groups. Conclusion untrained obese adolescents have more respiratory symptoms than their normal weight trained peers, and these factors are recommended to be used as a predictor of pulmonary function in assessment of obese children in epidemiological studies. In addition, obesity and inactivity can surcharge pulmonary function abnormalities in adolescents. PMID:25191449

  19. Assessing Airway Microbiota in Cystic Fibrosis: What More Should Be Done?

    PubMed

    LiPuma, John J

    2015-07-01

    The use of culture-independent methods has deepened our appreciation of the complexity of the bacterial communities that typically reside in the airways of persons with cystic fibrosis (CF). New insights into how changes in the structure of these communities relate to lung disease progression will likely raise expectations for more in-depth microbiologic analysis of CF respiratory specimens. An article in this issue of the Journal of Clinical Microbiology (W. G. Flight, A. Smith, C. Paisey, J. R. Marchesi, M. J. Bull, P. J. Norville, K. J. Mutton, A. K. Webb, R. J. Bright-Thomas, A. M. Jones, and E. Mahenthiralingam, J Clin Microbiol 53:2022-2029, 2015, http://dx.doi.org/10.1128/JCM.00432-15) describes the application of a culture-independent approach to the assessment of CF airway microbiota. PMID:25972422

  20. Assessment of the Airway Characteristics in Children with Cleft Lip and Palate using Cone Beam Computed Tomography

    PubMed Central

    Marwah, Nikhil

    2016-01-01

    ABSTRACT Objective: The aim of our study is to use cone beam computed tomography (CBCT) to assess the dimensional changes in the nasopharyngeal soft-tissue characteristics in children of Indian origin with repaired cleft lip and palate (CLP) and to compare the results with patients with ideal occlusion. Materials and methods: A sample of 20 children (10 girls, 10 boys) with repaired CLP was selected. Cone beam computed tomography scans were taken to measure the nasopharyngeal airway changes in terms of linear measurements and sagittal cross-sectional areas. Error analysis was performed to prevent systematic or random errors. Independent means t-tests and Pearson correlation analysis were used to evaluate sex differences and the correlations among the variables. Results: Nasopharyngeal soft-tissue characteristics were different in the control and the study groups. Subjects with repaired CLP had lesser lower aerial width, lower adenoidal width and lower airway width. The upper airway width was also significantly lesser. The retropalatal and the total airway area were significantly greater in the control group. Conclusion: The narrow pharyngeal airway in patients with CLP might result in functional impairment of breathing in patients. Further investigations are necessary to clarify the relationship between pharyngeal structure and airway function in patients with CLP. How to cite this article: Agarwal A, Marwah N. Assessment of the Airway Characteristics in Children with Cleft Lip and Palate using Cone Beam Computed Tomography. Int J Clin Pediatr Dent 2016;9(1):5-9. PMID:27274147

  1. The Assessment of Airway Maneuvers and Interventions in University Canadian Football, Ice Hockey, and Soccer Players

    PubMed Central

    Delaney, J. Scott; Al-Kashmiri, Ammar; Baylis, Penny-Jane; Troutman, Tracy; Aljufaili, Mahmood; Correa, José A.

    2011-01-01

    Abstract Context: Managing an airway in an unconscious athlete is a lifesaving skill that may be made more difficult by the recent changes in protective equipment. Different airway maneuvers and techniques may be required to help ventilate an unconscious athlete who is wearing full protective equipment. Objective: To assess the effectiveness of different airway maneuvers with football, ice hockey, and soccer players wearing full protective equipment. Design: Crossover study. Setting: University sports medicine clinic. Patients or Other Participants: A total of 146 university varsity athletes, consisting of 62 football, 45 ice hockey, and 39 soccer players. Intervention(s): Athletes were assessed for different airway and physical characteristics. Three investigators then evaluated the effectiveness of different bag-valve-mask (BVM) ventilation techniques in supine athletes who were wearing protective equipment while inline cervical spine immobilization was maintained. Main Outcome Measure(s): The effectiveness of 1-person BVM ventilation (1-BVM), 2-person BVM ventilation (2-BVM), and inline immobilization and ventilation (IIV) was judged by each investigator for each athlete using a 4-point rating scale. Results: All forms of ventilation were least difficult in soccer players and most difficult in football players. When compared with 1-BVM, both 2-BVM and IIV were deemed more effective by all investigators for all athletes. Interference from the helmet and stabilizer were common reasons for difficult ventilation in football and ice hockey players. Conclusions: Sports medicine professionals should practice and be comfortable with different ventilation techniques for athletes wearing full equipment. The use of a new ventilation technique, termed inline immobilization and ventilation, may be beneficial, especially when the number of responders is limited. PMID:21391796

  2. Mitotic Asynchrony Induces Transforming Growth Factor-β1 Secretion from Airway Epithelium

    PubMed Central

    Alcala, Sarah E.; Benton, Angela S.; Watson, Alan M.; Kureshi, Suraiya; Reeves, Erica M. K.; Damsker, Jesse; Wang, Zuyi; Nagaraju, Kanneboyina; Anderson, Julia; Williams, Aaron M.; Lee, Amber J. Y.; Hayes, Kathleen; Rose, Mary C.; Hoffman, Eric P.

    2014-01-01

    We recently proposed that mitotic asynchrony in repairing tissue may underlie chronic inflammation and fibrosis, where immune cell infiltration is secondary to proinflammatory cross-talk among asynchronously repairing adjacent tissues. Building on our previous finding that mitotic asynchrony is associated with proinflammatory/fibrotic cytokine secretion (e.g., transforming growth factor [TGF]-β1), here we provide evidence supporting cause-and-effect. Under normal conditions, primary airway epithelial basal cell populations undergo mitosis synchronously and do not secrete proinflammatory or profibrotic cytokines. However, when pairs of nonasthmatic cultures were mitotically synchronized at 12 hours off-set and then combined, the mixed cell populations secreted elevated levels of TGF-β1. This shows that mitotic asynchrony is not only associated with but is also causative of TGF-β1 secretion. The secreted cytokines and other mediators from asthmatic cells were not the cause of asynchronous regeneration; synchronously mitotic nonasthmatic epithelia exposed to conditioned media from asthmatic cells did not show changes in mitotic synchrony. We also tested if resynchronization of regenerating asthmatic airway epithelia reduces TGF-β1 secretion and found that pulse-dosed dexamethasone, simvastatin, and aphidicolin were all effective. We therefore propose a new model for chronic inflammatory and fibrotic conditions where an underlying factor is mitotic asynchrony. PMID:24669775

  3. The Homeobox Transcription Factor Cut Coordinates Patterning and Growth During Drosophila Airway Remodeling

    PubMed Central

    Pitsouli, Chrysoula; Perrimon, Norbert

    2014-01-01

    A fundamental question in developmental biology is how tissue growth and patterning are coordinately regulated to generate complex organs with characteristic shapes and sizes. We showed that in the developing primordium that produces the Drosophila adult trachea, the homeobox transcription factor Cut regulates both growth and patterning, and its effects depend on its abundance. Quantification of the abundance of Cut in the developing airway progenitors during late larval stage 3 revealed that the cells of the developing trachea had different amounts of Cut, with the most proliferative region having an intermediate amount of Cut and the region lacking Cut exhibiting differentiation. By manipulating Cut abundance, we showed that Cut functioned in different regions to regulate proliferation or patterning. Transcriptional profiling of progenitor populations with different amounts of Cut revealed the Wingless (known as Wnt in vertebrates) and Notch signaling pathways as positive and negative regulators of cut expression, respectively. Furthermore, we identified the gene encoding the receptor Breathless (Btl, known as fibroblast growth factor receptor in vertebrates) as a transcriptional target of Cut. Cut inhibited btl expression and tracheal differentiation to maintain the developing airway cells in a progenitor state. Thus, Cut functions in the integration of patterning and growth in a developing epithelial tissue. PMID:23423438

  4. Foxm1 Transcription Factor Is Critical for Proliferation and Differentiation of Clara Cells during Development of Conducting Airways

    PubMed Central

    Ustiyan, Vladimir; Wert, Susan E.; Ikegami, Machiko; Wang, I-Ching; Kalin, Tanya V.; Whitsett, Jeffrey A.; Kalinichenko, Kalinichenko

    2012-01-01

    SUMMARY Respiratory epithelial cells are derived from cell progenitors in the foregut endoderm that subsequently differentiate into the distinct cell types lining the conducting and alveolar regions of the lung. To identify transcriptional mechanisms regulating differentiation and maintenance of respiratory epithelial cells, we conditionally deleted Foxm1 transcription factor from the conducting airways of the developing mouse lung. Conditional deletion of Foxm1 from Clara cells, controlled by the Scgb1a1 promoter, dramatically altered airway structure and caused peribronchial fibrosis, resulting in airway hyperreactivity in adult mice. Deletion of Foxm1 inhibited proliferation of Clara cells and disrupted the normal patterning of epithelial cell differentiation in the bronchioles, causing squamous and goblet cell metaplasia, and the loss of Clara and ciliated cells. Surprisingly, conducting airways of Foxm1-deficient mice contained highly differentiated cuboidal type II epithelial cells that are normally restricted to the alveoli. Lineage tracing studies showed that the ectopic alveolar type II cells in Foxm1-deficient airways were derived from Clara cells. Deletion of Foxm1 inhibited Sox2 and Scgb1a1, both of which are critical for differentiation and function of Clara cells. In co-transfection experiments, Foxm1 directly bound to and induced transcriptional activity of Scgb1a1 and Sox2 promoters. Foxm1 is required for differentiation and maintenance of epithelial cells lining conducting airways. PMID:22885335

  5. Side-stream tobacco smoke-induced airway hyperresponsiveness in early postnatal period is involved nerve growth factor.

    PubMed

    Wu, Z-X; Hunter, D D; Batchelor, T P; Dey, R D

    2016-03-01

    Epidemiological studies have shown that children are more susceptible to adverse respiratory effects of passive smoking than adults. The goal of this study is to elucidate the possible neural mechanism induced by exposure to passive smoking during early life. Postnatal day (PD) 2 and PD 21 mice were exposed to side-stream tobacco smoke (SS), a surrogate to secondhand smoke, or filtered air (FA) for 10 consecutive days. Pulmonary function, substance P (SP) airway innervation, neurotrophin gene expression in lung and nerve growth factor (NGF) release in bronchoalveolar lavage (BAL) fluid were measured at different times after the last SS or FA exposure. Exposure to SS significantly altered pulmonary function in PD2, accompanied with an enhanced SP innervation in airway. However, exposure to SS during the later developmental period (PD21) did not appear to affect pulmonary function and SP innervation of the airways. Interestingly, SS exposure in PD2 group significantly induced an increased gene expression on NGF, and decreased NGF receptor P75 in lung; parallel with high levels of NGF protein in BAL. Furthermore, pretreatment with NGF antibody significantly diminished SS-induced airway hyperresponsivenss and the increased SP airway innervation in the PD2 group. These findings suggest that enhanced NGF released in the lung contributes to SS-enhanced SP tracheal innervation and airway responsiveness in early life. PMID:26638730

  6. Unidirectional Expiratory Valve Method to Assess Maximal Inspiratory Pressure in Individuals without Artificial Airway

    PubMed Central

    Grams, Samantha Torres; Kimoto, Karen Yumi Mota; Azevedo, Elen Moda de Oliveira; Lança, Marina; de Albuquerque, André Luis Pereira; de Brito, Christina May Moran; Yamaguti, Wellington Pereira

    2015-01-01

    Introduction Maximal Inspiratory Pressure (MIP) is considered an effective method to estimate strength of inspiratory muscles, but still leads to false positive diagnosis. Although MIP assessment with unidirectional expiratory valve method has been used in patients undergoing mechanical ventilation, no previous studies investigated the application of this method in subjects without artificial airway. Objectives This study aimed to compare the MIP values assessed by standard method (MIPsta) and by unidirectional expiratory valve method (MIPuni) in subjects with spontaneous breathing without artificial airway. MIPuni reproducibility was also evaluated. Methods This was a crossover design study, and 31 subjects performed MIPsta and MIPuni in a random order. MIPsta measured MIP maintaining negative pressure for at least one second after forceful expiration. MIPuni evaluated MIP using a unidirectional expiratory valve attached to a face mask and was conducted by two evaluators (A and B) at two moments (Tests 1 and 2) to determine interobserver and intraobserver reproducibility of MIP values. Intraclass correlation coefficient (ICC[2,1]) was used to determine intraobserver and interobserver reproducibility. Results The mean values for MIPuni were 14.3% higher (-117.3 ± 24.8 cmH2O) than the mean values for MIPsta (-102.5 ± 23.9 cmH2O) (p<0.001). Interobserver reproducibility assessment showed very high correlation for Test 1 (ICC[2,1] = 0.91), and high correlation for Test 2 (ICC[2,1] = 0.88). The assessment of the intraobserver reproducibility showed high correlation for evaluator A (ICC[2,1] = 0.86) and evaluator B (ICC[2,1] = 0.77). Conclusions MIPuni presented higher values when compared with MIPsta and proved to be reproducible in subjects with spontaneous breathing without artificial airway. PMID:26360255

  7. Hazard of CO₂ laser-induced airway fire in laryngeal surgery: experimental data of contributing factors.

    PubMed

    Stuermer, Konrad Johannes; Ayachi, Stefan; Gostian, Antoniu-O; Beutner, Dirk; Hüttenbrink, Karl-Bernd

    2013-09-01

    In carbon dioxide (CO2) laser surgery of the larynx, the potentially dangerous combination of laser-induced heat in an oxygen-enriched atmosphere typically occurs when jet ventilation is used or due to an insufficiently blocked endotracheal tube. Until now, no limitations for safe oxygen concentrations or laser intervals have been established. The aim of this study was to investigate and quantify the factors that may contribute to an airway fire in laryngeal laser surgery. Fat, muscle and cartilage were irradiated with a CO2 laser at 2, 4, 6 and 8 W in five different oxygen concentrations with and without smoke exhaustion. The time to ignition was recorded for each different experimental setup. Fat burnt fastest, followed by cartilage and muscle. The elevation of laser energy or oxygen concentration reduced the time to inflammation of any tissue. The elevation of oxygen by 10 % increases the risk of inflammation more than the elevation of laser power by 2 W. Under smoke exhaustion, inflammation and burning occurred delayed or were even inhibited at lower oxygen concentrations. Lasing in more than 50 % oxygen is comparatively dangerous and can cause airway fire in less than 5 s, especially when laser energies of more than 5 W are applied. In equal or lower than 50 % oxygen, an irradiation interval of 5 s can be considered a comparatively safe time limit to prevent inflammation in laryngeal laser surgery. Smoke exhaustion should always be applied. PMID:23636479

  8. Anatomic Optical Coherence Tomography of Upper Airways

    NASA Astrophysics Data System (ADS)

    Chin Loy, Anthony; Jing, Joseph; Zhang, Jun; Wang, Yong; Elghobashi, Said; Chen, Zhongping; Wong, Brian J. F.

    The upper airway is a complex and intricate system responsible for respiration, phonation, and deglutition. Obstruction of the upper airways afflicts an estimated 12-18 million Americans. Pharyngeal size and shape are important factors in the pathogenesis of airway obstructions. In addition, nocturnal loss in pharyngeal muscular tone combined with high pharyngeal resistance can lead to collapse of the airway and periodic partial or complete upper airway obstruction. Anatomical optical coherence tomography (OCT) has the potential to provide high-speed three-dimensional tomographic images of the airway lumen without the use of ionizing radiation. In this chapter we describe the methods behind endoscopic OCT imaging and processing to generate full three dimensional anatomical models of the human airway which can be used in conjunction with numerical simulation methods to assess areas of airway obstruction. Combining this structural information with flow dynamic simulations, we can better estimate the site and causes of airway obstruction and better select and design surgery for patients with obstructive sleep apnea.

  9. Assessment of upper airways measurements in patients with mandibular skeletal Class II malocclusion

    PubMed Central

    Silva, Nayanna Nadja e; Lacerda, Rosa Helena Wanderley; Silva, Alexandre Wellos Cunha; Ramos, Tania Braga

    2015-01-01

    Objective: Mandibular Class II malocclusions seem to interfere in upper airways measurements. The aim of this study was to assess the upper airways measurements of patients with skeletal Class II malocclusion in order to investigate the association between these measurements and the position and length of the mandible as well as mandibular growth trend, comparing the Class II group with a Class I one. Methods: A total of 80 lateral cephalograms from 80 individuals aged between 10 and 17 years old were assessed. Forty radiographs of Class I malocclusion individuals were matched by age with forty radiographs of individuals with mandibular Class II malocclusion. McNamara Jr., Ricketts, Downs and Jarabak's measurements were used for cephalometric evaluation. Data were submitted to descriptive and inferential statistical analysis by means of SPSS 20.0 statistical package. Student's t-test, Pearson correlation and intraclass correlation coefficient were used. A 95% confidence interval and 5% significance level were adopted to interpret the results. Results: There were differences between groups. Oropharynx and nasopharynx sizes as well as mandibular position and length were found to be reduced in Class II individuals. There was a statistically significant positive correlation between the size of the oropharynx and Xi-Pm, Co-Gn and SNB measurements. In addition, the size of the nasopharynx was found to be correlated with Xi-Pm, Co-Gn, facial depth, SNB, facial axis and FMA. Conclusion: Individuals with mandibular Class II malocclusion were shown to have upper airways measurements diminished. There was a correlation between mandibular length and position and the size of oropharynx and nasopharynx. PMID:26560826

  10. ISO-1, a macrophage migration inhibitory factor antagonist, inhibits airway remodeling in a murine model of chronic asthma.

    PubMed

    Chen, Pei-Fen; Luo, Ya-ling; Wang, Wei; Wang, Jiang-xin; Lai, Wen-yan; Hu, Si-ming; Cheng, Kai Fan; Al-Abed, Yousef

    2010-01-01

    Airway remodeling is the process of airway structural change that occurs in patients with asthma in response to persistent inflammation and leads to increasing disease severity. Drugs that decrease this persistent inflammation play a crucial role in managing asthma episodes. Mice sensitized (by intraperitoneal administration) and then challenged (by inhalation) with ovalbumin (OVA) develop an extensive eosinophilic inflammatory response, goblet cell hyperplasia, collagen deposition, airway smooth muscle thickening, and airway wall area increase, similar to pathologies observed in human asthma. We used OVA-sensitized/challenged mice as a murine model of chronic allergic airway inflammation with subepithelial fibrosis (i.e., asthma). In this OVA mouse model, mRNA and protein of macrophage migration inhibitory factor (MIF) are upregulated, a response similar to what has been observed in the pathogenesis of acute inflammation in human asthma. We hypothesized that MIF induces transforming growth factor-β1 (TGF-β1) synthesis, which has been shown to play an important role in asthma and airway remodeling. To explore the role of MIF in the development of airway remodeling, we evaluated the effects of an MIF small-molecule antagonist, (S,R)3-(4-hy-droxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester (ISO-1), on pathologies associated with the airway-remodeling process in the OVA mouse model. We found that administration of ISO-1 significantly mitigated all symptoms caused by OVA treatment. In addition, the treatment of OVA-sensitized mice with the MIF antagonist ISO-1 significantly reduced TGF-β1 mRNA levels in pulmonary tissue and its protein level in bronchial alveolar lavage fluid supernatants. We believe the repression of MIF in the ISO-1 treatment group led to the significant suppression observed in the inflammatory responses associated with the allergen-induced lung inflammation and fibrosis in our murine asthma (OVA) model. Our results implicate a

  11. The effect of platelet activating factor antagonist on ozone-induced airway inflammation and bronchial hyperresponsiveness in guinea pigs

    SciTech Connect

    Tan, W.C.; Bethel, R.A. )

    1992-10-01

    We investigated the role of platelet-activating factor (PAF) in ozone-induced airway responses by examining the effects of L659,989, a potent PAF antagonist, on bronchial hyperresponsiveness and airway inflammation. Twenty-four male guinea pigs were studied in four equal groups. Total lung resistance (RL) in intubated and spontaneously breathing animals was measured in a constant-volume body plethysmograph. Dose-response curves to methacholine were determined in all animals at the start of the experiment. These were repeated on a separate day after the following types of treatments: air exposure in Group 1, intraperitoneally administered alcohol and air exposure in Group 2; intraperitoneally administered alcohol and ozone exposure in Group 3, and intraperitoneally administered L659,989 (a specific PAF antagonist), 5 mg/kg dissolved in alcohol, and ozone exposure in Group 4. Bronchoalveolar lavage (BAL) was performed after the second methacholine challenge, and the bronchial mucosa was also examined for inflammatory cells. Exposure to 3 ppm ozone for 2 h resulted in a three-doubling concentration increase in bronchial responsiveness, which was not significantly inhibited by prior treatment with L659,989. Ozone induced a 1.8-fold increase in BAL total cell count, increased eosinophilic influx into the airways, and increased eosinophilic infiltration in the bronchial mucosa, which were all not inhibited by L659,989 pretreatment. The results suggest that PAF may not have an essential role in ozone-induced airway hyperresponsiveness and nonallergic airway inflammation.

  12. Assessment of Mini-dose Succinylcholine Effect on FacilitatingLaryngeal Mask Airway Insertion

    PubMed Central

    Aghamohammadi, Dawood; Eydi, Mahmood; Hosseinzadeh, Hamzeh; Amiri Rahimi, Maryam; EJ Golzari, Samad

    2013-01-01

    Introduction: Laryngeal Mask Airway (LMA) has gained wide acceptance for routine airway management and with increasing emphasis on day care surgery it is widely used. The aim of this study was to assess the effects of mini dose succinylcholine (0.1mg/kg) with semi-inflated cuff on facilitation of laryngeal mask airway insertion in order to achieve more satisfaction yet less complications . Methods: In a randomized double-blinded study, sixty ASA 1, 2 and 3 patients aged 20-60 years scheduled for urologic surgical procedures were included. Thirty patients received succinylcholine (Group S), and thirty received 0.9% sodium choride as a placebo (Group C). Results: Coughing occured in 33.3% of patients in the control group and there was no incidence in succ group (P=0.002). Head or limb movement occurred in 70% of the patients in the control group vs. 10% in succ group (P<0.001). Laryngospasm occurred in 36.6 % of the patients in the control group but there was no incidence in succ group (P=0.004). Additional propofol was required in 53% of the patients in control group vs. 10% for succ group (P=0.001). Ease of insertion and first successfull attempt of LMA were achieved in 93.3% and 90% of the patients respectively in group S (P<0.05). Myalgia and sore throat occurred in 66.7 % of patients in the group C in comparison with 33.3% in group S (P=0.06).Conclusion: The combination of propofol with mini dose succinylcholine, provided a significantly better method for LMA insertion, while reduced propofol doses were needed and number of attempts decreased. PMID:24251004

  13. Assessment of upper airway dynamics in awake patients with sleep apnea using phrenic nerve stimulation.

    PubMed

    Sériès, F; Straus, C; Demoule, A; Attali, V; Arnulf, I; Derenne, J P; Similowski, T

    2000-09-01

    Phrenic nerve stimulation can reproduce during wakefulness the dissociation between upper airway and inspiratory muscles that is associated with obstructive sleep-related breathing disorders. This could provide a useful management tool in the study of passive upper airway (UA) dynamics during wakefulness in patients with the obstructive sleep apnea-hypopnea syndrome (OSAHS). To assess the feasibility of the technique in this setting, we studied the dynamics of diaphragm twitch-associated inspiratory flow in eight patients with OSAHS. Cervical magnetic stimulation (CMS) and bilateral anterior magnetic phrenic stimulation (BAMPS) were applied at end-expiration during exclusive nasal breathing. Electrical phrenic nerve stimulation (ES) proved not feasible. The driving pressure and the respiratory resistance at peak twitch esophageal pressure obtained at maximal stimulation intensity were significantly higher with BAMPS than with CMS. A twitch-flow limitation pattern was observed in seven of eight subjects; VI(max) values of flow-limited twitches obtained at 100% stimulation intensity was 0.81 +/- 0.5 L/s with BAMPS and 0.87 +/- 0.5 L/s with CMS (p = 0.4). The number of flow-limited BAMPS twitches dropped from an average 77.5% to 18.4% with nasal continuous positive airway pressure (CPAP) levels corresponding to the patient's home treatment. We conclude that (1) BAMPS is potentially a useful tool to evaluate the dynamics of flow through the passive UA in awake OSAHS patients, (2) BAMPS may be superior to CMS in evaluating UA properties in OSAHS. PMID:10988085

  14. Influence of radiation dose and reconstruction algorithm in MDCT assessment of airway wall thickness: A phantom study

    SciTech Connect

    Gomez-Cardona, Daniel; Nagle, Scott K.; Li, Ke; Chen, Guang-Hong; Robinson, Terry E.

    2015-10-15

    Purpose: Wall thickness (WT) is an airway feature of great interest for the assessment of morphological changes in the lung parenchyma. Multidetector computed tomography (MDCT) has recently been used to evaluate airway WT, but the potential risk of radiation-induced carcinogenesis—particularly in younger patients—might limit a wider use of this imaging method in clinical practice. The recent commercial implementation of the statistical model-based iterative reconstruction (MBIR) algorithm, instead of the conventional filtered back projection (FBP) algorithm, has enabled considerable radiation dose reduction in many other clinical applications of MDCT. The purpose of this work was to study the impact of radiation dose and MBIR in the MDCT assessment of airway WT. Methods: An airway phantom was scanned using a clinical MDCT system (Discovery CT750 HD, GE Healthcare) at 4 kV levels and 5 mAs levels. Both FBP and a commercial implementation of MBIR (Veo{sup TM}, GE Healthcare) were used to reconstruct CT images of the airways. For each kV–mAs combination and each reconstruction algorithm, the contrast-to-noise ratio (CNR) of the airways was measured, and the WT of each airway was measured and compared with the nominal value; the relative bias and the angular standard deviation in the measured WT were calculated. For each airway and reconstruction algorithm, the overall performance of WT quantification across all of the 20 kV–mAs combinations was quantified by the sum of squares (SSQs) of the difference between the measured and nominal WT values. Finally, the particular kV–mAs combination and reconstruction algorithm that minimized radiation dose while still achieving a reference WT quantification accuracy level was chosen as the optimal acquisition and reconstruction settings. Results: The wall thicknesses of seven airways of different sizes were analyzed in the study. Compared with FBP, MBIR improved the CNR of the airways, particularly at low radiation dose

  15. The Oligo Fucoidan Inhibits Platelet-Derived Growth Factor-Stimulated Proliferation of Airway Smooth Muscle Cells

    PubMed Central

    Yang, Chao-Huei; Tsao, Chiung-Fang; Ko, Wang-Sheng; Chiou, Ya-Ling

    2016-01-01

    In the pathogenesis of asthma, the proliferation of airway smooth muscle cells (ASMCs) is a key factor in airway remodeling and causes airway narrowing. In addition, ASMCs are also the effector cells of airway inflammation. Fucoidan extracted from marine brown algae polysaccharides has antiviral, antioxidant, antimicrobial, anticlotting, and anticancer properties; however, its effectiveness for asthma has not been elucidated thus far. Platelet-derived growth factor (PDGF)-treated primary ASMCs were cultured with or without oligo-fucoidan (100, 500, or 1000 µg/mL) to evaluate its effects on cell proliferation, cell cycle, apoptosis, and Akt, ERK1/2 signaling pathway. We found that PDGF (40 ng/mL) increased the proliferation of ASMCs by 2.5-fold after 48 h (p < 0.05). Oligo-fucoidan reduced the proliferation of PDGF-stimulated ASMCs by 75%–99% after 48 h (p < 0.05) and induced G1/G0 cell cycle arrest, but did not induce apoptosis. Further, oligo-fucoidan supplementation reduced PDGF-stimulated extracellular signal-regulated kinase (ERK1/2), Akt, and nuclear factor (NF)-κB phosphorylation. Taken together, oligo-fucoidan supplementation might reduce proliferation of PDGF-treated ASMCs through the suppression of ERK1/2 and Akt phosphorylation and NF-κB activation. The results provide basis for future animal experiments and human trials. PMID:26761017

  16. The transcription factor PU.1 promotes alternative macrophage polarization and asthmatic airway inflammation.

    PubMed

    Qian, Feng; Deng, Jing; Lee, Yong Gyu; Zhu, Jimmy; Karpurapu, Manjula; Chung, Sangwoon; Zheng, Jun-Nian; Xiao, Lei; Park, Gye Young; Christman, John W

    2015-12-01

    The transcription factor PU.1 is involved in regulation of macrophage differentiation and maturation. However, the role of PU.1 in alternatively activated macrophage (AAM) and asthmatic inflammation has yet been investigated. Here we report that PU.1 serves as a critical regulator of AAM polarization and promotes the pathological progress of asthmatic airway inflammation. In response to the challenge of DRA (dust mite, ragweed, and Aspergillus) allergens, conditional PU.1-deficient (PU/ER(T)(+/-)) mice displayed attenuated allergic airway inflammation, including decreased alveolar eosinophil infiltration and reduced production of IgE, which were associated with decreased mucous glands and goblet cell hyperplasia. The reduced asthmatic inflammation in PU/ER(T)(+/-) mice was restored by adoptive transfer of IL-4-induced wild-type (WT) macrophages. Moreover, after treating PU/ER(T)(+/-) mice with tamoxifen to rescue PU.1 function, the allergic asthmatic inflammation was significantly restored. In vitro studies demonstrate that treatment of PU.1-deficient macrophages with IL-4 attenuated the expression of chitinase 3-like 3 (Ym-1) and resistin-like molecule alpha 1 (Fizz-1), two specific markers of AAM polarization. In addition, PU.1 expression in macrophages was inducible in response to IL-4 challenge, which was associated with phosphorylation of signal transducer and activator of transcription 6 (STAT6). Furthermore, DRA challenge in sensitized mice almost abrogated gene expression of Ym-1 and Fizz-1 in lung tissues of PU/ER(T)(+/-) mice compared with WT mice. These data, all together, indicate that PU.1 plays a critical role in AAM polarization and asthmatic inflammation. PMID:26101328

  17. Effect of ozone treatment on airway reactivity and epithelium-derived relaxing factor in guinea pigs.

    PubMed

    Fedan, J S; Millecchia, L L; Johnston, R A; Rengasamy, A; Hubbs, A; Dey, R D; Yuan, L X; Watson, D; Goldsmith, W T; Reynolds, J S; Orsini, L; Dortch-Carnes, J; Cutler, D; Frazer, D G

    2000-06-01

    Ozone (O(3)) is toxic to respiratory epithelium and causes airway inflammation and hyperreactivity. To evaluate the role of the epithelium in the development of hyperreactivity, we examined in guinea pigs the effects of inhaled O(3) (3 ppm for 1 h; 0-24 h after exposure) on 1) reactivity to inhaled methacholine (MCh), 2) reactivity of the isolated, perfused trachea (IPT) to MCh, 3) epithelium-derived relaxing factor (EpDRF)-mediated relaxations of IPT induced by mucosal hyperosmolar solutions, 4) neurogenic contraction and relaxation responses, 5) transepithelial potential difference, and 6) microscopic analysis of nitrotyrosine immunofluorescence, substance P fiber density, and tracheal morphology. At 0 h, O(3) caused hyperreactivity to inhaled MCh and mucosally but not serosally applied MCh in IPT (only in the presence of the epithelium) and a decrease in transepithelial potential difference. Inhibition of EpDRF-induced relaxation responses occurred at 2 h. All of these changes returned to control by 12 to 18 h. O(3) had no effect on neurogenic responses. Nitrotyrosine immunofluorescence appeared in the trachea at 0 h in detached epithelial cell ghosts and in intrapulmonary airways by 6 h. Substance P fiber density was elevated in smooth muscle at 0 and 18 h but not in epithelium or lamina propria of intrapulmonary and extrapulmonary bronchi. Loss of cilia and mucosubstances in the mucosa occurred at 0 h; the epithelium became markedly attenuated over 12 to 24 h. A reversible increase in epithelial permeability and a decrease in EpDRF production may contribute to O(3)-induced hyperreactivity to MCh. PMID:10869370

  18. Airway compromise in the fetus and neonate: Prenatal assessment and perinatal management.

    PubMed

    Ryan, Greg; Somme, Stig; Crombleholme, Timothy M

    2016-08-01

    The fetus with a potentially obstructed airway can be identified on routine antenatal imaging. These cases should be referred to fetal care centers, which have the necessary expertise to fully evaluate and manage these fetuses and neonates appropriately. Complete airway obstruction may result in fetal hydrops and intrauterine demise. If a newborn infant has a compromised airway at delivery, the inability to secure its airway quickly may result in a hypoxic cerebral insult or death. In the most severely affected cases, prenatal, perinatal, or postnatal surgical intervention may be necessary. The timing of such an intervention will depend on the exact cause of the airway obstruction, other associated findings and the anticipated difficulty in establishing an airway at delivery. Fetal ultrasound and magnetic resonance imaging can differentiate between intrinsic and extrinsic airway obstruction, which allows for the optimal planning and management of the delivery and neonatal resuscitation. PMID:27084444

  19. Risk Factor Assessment Branch (RFAB)

    Cancer.gov

    The Risk Factor Assessment Branch (RFAB) focuses on the development, evaluation, and dissemination of high-quality risk factor metrics, methods, tools, technologies, and resources for use across the cancer research continuum, and the assessment of cancer-related risk factors in the population.

  20. Ets homologous factor regulates pathways controlling response to injury in airway epithelial cells.

    PubMed

    Fossum, Sara L; Mutolo, Michael J; Yang, Rui; Dang, Hong; O'Neal, Wanda K; Knowles, Michael R; Leir, Shih-Hsing; Harris, Ann

    2014-12-16

    Ets homologous factor (EHF) is an Ets family transcription factor expressed in many epithelial cell types including those lining the respiratory system. Disruption of the airway epithelium is central to many lung diseases, and a network of transcription factors coordinates its normal function. EHF can act as a transcriptional activator or a repressor, though its targets in lung epithelial cells are largely uncharacterized. Chromatin immunoprecipitation followed by deep sequencing (ChIP-seq), showed that the majority of EHF binding sites in lung epithelial cells are intergenic or intronic and coincide with putative enhancers, marked by specific histone modifications. EHF occupies many genomic sites that are close to genes involved in intercellular and cell-matrix adhesion. RNA-seq after EHF depletion or overexpression showed significant alterations in the expression of genes involved in response to wounding. EHF knockdown also targeted genes in pathways of epithelial development and differentiation and locomotory behavior. These changes in gene expression coincided with alterations in cellular phenotype including slowed wound closure and increased transepithelial resistance. Our data suggest that EHF regulates gene pathways critical for epithelial response to injury, including those involved in maintenance of barrier function, inflammation and efficient wound repair. PMID:25414352

  1. NEU1 Sialidase Expressed in Human Airway Epithelia Regulates Epidermal Growth Factor Receptor (EGFR) and MUC1 Protein Signaling*

    PubMed Central

    Lillehoj, Erik P.; Hyun, Sang Won; Feng, Chiguang; Zhang, Lei; Liu, Anguo; Guang, Wei; Nguyen, Chinh; Luzina, Irina G.; Atamas, Sergei P.; Passaniti, Antonino; Twaddell, William S.; Puché, Adam C.; Wang, Lai-Xi; Cross, Alan S.; Goldblum, Simeon E.

    2012-01-01

    Epithelial cells (ECs) lining the airways provide a protective barrier between the external environment and the internal host milieu. These same airway epithelia express receptors that respond to danger signals and initiate repair programs. Because the sialylation state of a receptor can influence its function and is dictated in part by sialidase activity, we asked whether airway epithelia express catalytically active sialidase(s). Human primary small airway and A549 ECs expressed NEU1 sialidase at the mRNA and protein levels, and NEU1 accounted for >70% of EC sialidase activity. Blotting with Maackia amurensis and peanut agglutinin lectins established epidermal growth factor receptor (EGFR) and MUC1 as in vivo substrates for NEU1. NEU1 associated with EGFR and MUC1, and NEU1-EGFR association was regulated by EGF stimulation. NEU1 overexpression diminished EGF-stimulated EGFR Tyr-1068 autophosphorylation by up to 44% but enhanced MUC1-dependent Pseudomonas aeruginosa adhesion by 1.6–1.7-fold and flagellin-stimulated ERK1/2 activation by 1.7–1.9-fold. In contrast, NEU1 depletion increased EGFR activation (1.5-fold) and diminished MUC1-mediated bacterial adhesion (38–56%) and signaling (73%). These data indicate for the first time that human airway epithelia express catalytically active NEU1 sialidase that regulates EGFR- and MUC1-dependent signaling and bacterial adhesion. NEU1 catalytic activity may offer an additional level of regulation over the airway epithelial response to ligands, pathogens, and injurious stimuli. PMID:22247545

  2. Functional assessment of expiratory flow pattern in feline lower airway disease.

    PubMed

    Lin, Chung-Hui; Lee, Jih-Jong; Liu, Chen-Hsuan

    2014-08-01

    Feline lower airway disease (FLAD) is a chronic respiratory disease of which there is a lack of information on functional assessment in current veterinary medicine. The purposes of this study were to investigate expiratory pattern and evaluate the diagnostic utility of functional parameters in cats with FLAD. Thirty-three client-owned cats (23 FLAD cats and 10 control cats) were studied. Under quiet tidal breathing, pseudo-tidal breathing flow-volume loop (pTBFVL) was obtained from a barometric whole body plethysmography (BWBP) device. There were significant differences in the shapes of expiratory, but not inspiratory, curves between FLAD and control cats. The incidence of the presence of concave expiratory curve indicating lower airway obstruction was 74% in FLAD cats. To assess the diagnostic utility of pTBFVL indices in cats with FLAD, area under the receiver-operator curve was 0.86 for PEF/EF50 (peak expiratory flow divided by expiratory flow at end expiratory volume plus 50% tidal volume); a cuff-off value of PEF/EF50 >1.51 distinguished normal from FLAD (73.9% sensitivity, 100% specificity). There were no significant differences in traditionally measured BWBP parameters (ie, enhanced pause) between cats with and without FLAD in the present study. In conclusion, underlying change on expiratory flow pattern during natural tidal breathing existed in FLAD cats, and selected pTBFVL indices were useful in discriminating FLAD from normal cats. Tidal breathing pattern depicted by pseudoflow-pseudovolume loops from a BWBP system could be a non-invasive tool for functional assessment in client-owned cats. PMID:24327372

  3. Regulation of airway neurogenic inflammation by neutral endopeptidase.

    PubMed

    Di Maria, G U; Bellofiore, S; Geppetti, P

    1998-12-01

    Airway neurogenic inflammation is caused by tachykinins released from peripheral nerve endings of sensory neurons within the airways, and is characterized by plasma protein extravasation, airway smooth muscle contraction and increased secretion of mucus. Tachykinins are degraded and inactivated by neutral endopeptidase (NEP), a membrane-bound metallopeptidase, which is located mainly at the surface of airway epithelial cells, but is also present in airway smooth muscle cells, submucosal gland cells and fibroblasts. The key role of NEP in limiting and regulating the neurogenic inflammation provoked by different stimuli has been demonstrated in a large series of studies published in recent years. It has also been shown that a variety of factors, which are relevant for airway diseases, including viral infections, allergen exposure, inhalation of cigarette smoke and other respiratory irritants, is able to reduce NEP activity, thus enhancing the effects of tachykinins within the airways. On the basis of these observations, the reduction of neutral endopeptidase activity may be regarded as a factor that switches neurogenic airway responses from their physiological and protective functions to a detrimental role that increases and perpetuates airway inflammation. However, further studies are needed to assess the role of neutral endopeptidase down regulation in the pathogenesis of asthma and other inflammatory airway diseases. PMID:9877509

  4. Phenotyping airways disease: an A to E approach.

    PubMed

    Gonem, S; Raj, V; Wardlaw, A J; Pavord, I D; Green, R; Siddiqui, S

    2012-12-01

    The airway diseases asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous conditions with overlapping pathophysiological and clinical features. It has previously been proposed that this heterogeneity may be characterized in terms of five relatively independent domains labelled from A to E, namely airway hyperresponsiveness (AHR), bronchitis, cough reflex hypersensitivity, damage to the airways and surrounding lung parenchyma, and extrapulmonary factors. Airway hyperresponsiveness occurs in both asthma and COPD, accounting for variable day to day symptoms, although the mechanisms most likely differ between the two conditions. Bronchitis, or airway inflammation, may be predominantly eosinophilic or neutrophilic, with different treatments required for each. Cough reflex hypersensitivity is thought to underlie the chronic dry cough out of proportion to other symptoms that can occur in association with airways disease. Structural changes associated with airway disease (damage) include bronchial wall thickening, airway smooth muscle hypertrophy, bronchiectasis and emphysema. Finally, a variety of extrapulmonary factors may impact upon airway disease, including rhinosinusitis, gastroesophageal reflux disease, obesity and dysfunctional breathing. This article discusses the A to E concept in detail and describes how this framework may be used to assess and treat patients with airway diseases in the clinic. PMID:23181785

  5. New insights on the viral and host factors contributing to the airway pathogenesis caused by the respiratory syncytial virus.

    PubMed

    Lay, Margarita K; Bueno, Susan M; Gálvez, Nicolás; Riedel, Claudia A; Kalergis, Alexis M

    2016-09-01

    The respiratory syncytial virus (RSV) is the most prevalent etiological agent of lower respiratory tract infections and the first cause of hospitalization in infants due to respiratory disease worldwide. However, efforts to develop safe and effective vaccines and antivirals have been challenged by an incomplete understanding of the RSV pathogenesis and the host immune response to RSV infection in the airways. Here, we discuss recent advances in understanding the interaction between RSV and the epithelium to induce pathogenesis in the airways, such as the role of the RSV NS2 protein in the airway epithelium, as well as the events involved in the RSV entry process. In addition, we summarize the cellular factors produced by airway epithelial cells (AECs) in response to RSV infection that lead to the activation of innate and adaptive immune responses, inducing lung inflammation and disease. Further, we discuss the possible contribution of a recently identified cytokine, thymic stromal lymphopoitein (TSLP), in the lung immunopathology caused by RSV. PMID:26119025

  6. Reliability and validity of a tool to assess airway management skills in anesthesia trainees

    PubMed Central

    Ahmed, Aliya; Khan, Fauzia Anis; Ismail, Samina

    2016-01-01

    Background and Aims: Gaining expertise in procedural skills is essential for achieving clinical competence during anesthesia training. Supervisors have the important responsibility of deciding when the trainee can be allowed to perform various procedures without direct supervision while ensuring patient safety. This requires robust and reliable assessment techniques. Airway management with bag-mask ventilation and tracheal intubation are routinely performed by anesthesia trainees at induction of anesthesia and to save lives during a cardiorespiratory arrest. The purpose of this study was to evaluate the construct validity, and inter-rater and test-retest reliability of a tool designed to assess competence in bag-mask ventilation followed by tracheal intubation in anesthesia trainees. Material and Methods: Informed consent was obtained from all participants. Tracheal intubation and bag-mask ventilation skills in 10 junior and 10 senior anesthesia trainees were assessed by two investigators on two occasions at a 3-4 weeks interval, using a procedure-specific assessment tool. Results: Average kappa value for inter-rater reliability was 0.91 and 0.99 for the first and second assessments, respectively, with an average agreement of 95%. The average agreement for test-retest reliability was 82% with a kappa value of 0.39. Senior trainees obtained higher scores compared to junior trainees in all areas of assessment, with a significant difference for patient positioning, preoxygenation, and laryngoscopy technique, depicting good construct validity. Conclusion: The tool designed to assess bag-mask ventilation and tracheal intubation skills in anesthesia trainees demonstrated excellent inter-rater reliability, fair test-retest reliability, and good construct validity. The authors recommend its use for formative and summative assessment of junior anesthesia trainees.

  7. IL-13 Augments Compressive Stress-Induced Tissue Factor Expression in Human Airway Epithelial Cells.

    PubMed

    Mitchel, Jennifer A; Antoniak, Silvio; Lee, Joo-Hyeon; Kim, Sae-Hoon; McGill, Maureen; Kasahara, David I; Randell, Scott H; Israel, Elliot; Shore, Stephanie A; Mackman, Nigel; Park, Jin-Ah

    2016-04-01

    Tissue factor (TF) is best known as a cellular initiator of coagulation, but it is also a multifunctional protein that has been implicated in multiple pathophysiologic conditions, including asthma. In the lung, airway epithelial cells express TF, but it is unknown how TF expression is regulated by asthma-associated mediators. We investigated the role of IL-13, a type 2 cytokine, alone and in combination with compressive stress, which mimics asthmatic bronchoconstriction, on TF expression and release of TF-positive extracellular vesicles from primary normal human bronchial epithelial cells. Well-differentiated normal human bronchial epithelial cells were treated with IL-13 and compressive stress, alone and in combination. TF mRNA, protein and activity were measured in the cells and conditioned media. TF was also measured in the bronchoalveolar lavage (BAL) fluid of allergen-challenged mice and patients with asthma. IL-13 and compressive stress increased TF expression, but only compressive stress induced TF-positive extracellular vesicle release. Pretreatment with IL-13 augmented compressive stress-induced TF expression and release. TF protein and activity in BAL fluid were increased in allergen-sensitized and -challenged mice. TF was elevated in the BAL fluid of patients with mild asthma after an allergen challenge. Our in vitro and in vivo data indicate close cooperation between mechanical and inflammatory stimuli on TF expression and release of TF-positive extracellular vesicles in the lungs, which may contribute to pathophysiology of asthma. PMID:26407210

  8. Risk Factors Associated with Irreversible Airway Obstruction in Asthma: A Systematic Review and Meta-Analysis

    PubMed Central

    Zhang, Lanlan; He, Lixiu; Gong, Jin; Liu, Chuntao

    2016-01-01

    Irreversible airway obstruction (IAO) is a subtype of asthma and relates to poorer prognosis in some asthma patients. However, the prevalence and risk factors for IAO are unknown. A systematic review regarding controlled clinical studies (cohort, case-control studies) on IAO asthma in adult and/or children affected by asthma/early wheeze was performed. Eighteen papers were identified in this study. It was reported that the incidence of IAO at random effects or fixed effects in severe asthma and nonsevere asthma was 0.54 (95% CI: 0.45–0.62) and 0.16 (95% CI: 0.12–0.20), respectively. In IAO asthma, the pooled odds ratio (OR) related to smoking exposure was 2.22 (95% CI: 1.82–2.73), the OR for male, smoking, and fractional exhaled nitric oxide (FENO) was 2.22 (95% CI: 1.82–2.7), 1.79 (95% CI: 1.46–2.19), and 2.16 (95% CI: 1.05–4.43), respectively, suggesting these factors increase the risk of IAO. However, a decreased OR in IAO asthma was observed due to rhinitis (OR = 0.31, 95% CI: 0.24–0.40), atopy (OR = 0.584, 95% CI: 0.466–0.732), and atopic dermatitis (OR = 0.60, 95% CI: 0.42–0.85), indicating these factors are associated with reduced risk of IAO. IAO in asthma is associated with gender, smoking, FENO, rhinitis, atopy, and atopic dermatitis. PMID:27119087

  9. Reactive airways dysfunction syndrome due to chlorine: sequential bronchial biopsies and functional assessment.

    PubMed

    Lemière, C; Malo, J L; Boutet, M

    1997-01-01

    Very little information is available on the acute histopathological bronchial alterations caused by reactive airways dysfunction syndrome (RADS). We had the opportunity to carry out sequential bronchial biopsies in a subject with RADS due to chlorine (60 h, 15 days, 2 and 5 months after the acute exposure), and also to assess spirometry and bronchial responsiveness to methacholine. A 36 year old worker in a water-filtration plant (nonsmoker) abruptly inhaled high concentrations of chlorine on September 12, 1994. He experienced immediate nasal and throat burning, retrosternal burning and wheezing, and these symptoms persisted during and after the workshift. Two days later, he complained of retrosternal burning, dyspnoea and wheezing. Inspiratory wheezing was documented. His forced expiratory volume in one second (FEV1) was 66% of predicted and the provocative concentration of methacholine causing a 20% fall in FEV1 (PC20) was slightly abnormal (2.5 mg.mL-1). On the following day, the patient underwent bronchial biopsies, which showed almost complete replacement of the epithelium by a fibrinohaemorhagic exsudate. The subject was prescribed inhaled steroids. Fifteen days after the accident, the PC20 was improved to 6 mg.mL-1. Bronchial biopsies showed considerable epithelial desquamation with an inflammatory exudate and swelling of the subepithelial space. Five weeks after the accident, the PC20 was normal (57 mg.mL-1). Inhaled steroids were stopped. Two months after the accident, the PC20 deteriorated to 4 mg.mL-1. Biopsies then showed regeneration of the epithelium by basal cells and there was still a pronounced inflammatory infiltrate. Inhaled steroids were restarted. Three and five months later, the PC20 was normal (24 mg.mL-1). Bronchial biopsies showed a greatly improved epithelium and reduction of the inflammatory infiltrate. This case report shows that reactive airways dysfunction syndrome can cause acute, marked, though partially reversible, histological

  10. Assessment of Human Factors

    NASA Technical Reports Server (NTRS)

    Mount, Frances; Foley, Tico

    1999-01-01

    Human Factors Engineering, often referred to as Ergonomics, is a science that applies a detailed understanding of human characteristics, capabilities, and limitations to the design, evaluation, and operation of environments, tools, and systems for work and daily living. Human Factors is the investigation, design, and evaluation of equipment, techniques, procedures, facilities, and human interfaces, and encompasses all aspects of human activity from manual labor to mental processing and leisure time enjoyments. In spaceflight applications, human factors engineering seeks to: (1) ensure that a task can be accomplished, (2) maintain productivity during spaceflight, and (3) ensure the habitability of the pressurized living areas. DSO 904 served as a vehicle for the verification and elucidation of human factors principles and tools in the microgravity environment. Over six flights, twelve topics were investigated. This study documented the strengths and limitations of human operators in a complex, multifaceted, and unique environment. By focusing on the man-machine interface in space flight activities, it was determined which designs allow astronauts to be optimally productive during valuable and costly space flights. Among the most promising areas of inquiry were procedures, tools, habitat, environmental conditions, tasking, work load, flexibility, and individual control over work.

  11. Nerve growth factor and neurotrophin-3 mediate survival of pulmonary plasma cells during the allergic airway inflammation.

    PubMed

    Abram, Melanie; Wegmann, Michael; Fokuhl, Verena; Sonar, Sanchaita; Luger, Elke Olga; Kerzel, Sebastian; Radbruch, Andreas; Renz, Harald; Zemlin, Michael

    2009-04-15

    Allergen-specific Abs play a pivotal role in the induction and maintenance of allergic airway inflammation. During secondary immune responses, plasma cell survival and Ab production is mediated by extrinsic factors provided by the local environment (survival niches). It is unknown whether neurotrophins, a characteristic marker of allergic airway inflammation, influence plasma cell survival in the lung. Using a mouse model of allergic asthma, we found that plasma cells from the lung and spleen are distinct subpopulations exhibiting differential expression patterns of neurotrophins and their receptors (Trks). In vitro, the nerve growth factor (NGF) and neurotrophin-3 (NT3) led to a dose-dependent increase in viability of isolated pulmonary plasma cells due to up-regulation of the antiapoptotic Bcl2 pathway. In parallel, the expression of transcription factors that stimulate the production of immunoglobulins (X-box binding protein 1 and NF-kappaB subunit RelA) was enhanced in plasma cells treated with NGF and NT3. These findings were supported in vivo. When the NGF pathway was blocked by intranasal application of a selective TrkA inhibitor, sensitized mice showed reduced numbers of pulmonary plasma cells and developed lower levels of allergen-specific and total serum IgE in response to OVA inhalation. This suggests that in the allergic airway inflammation, NGF/TrkA-mediated pulmonary IgE production contributes significantly to serum-IgE levels. We conclude that the neurotrophins NGF and NT3 act as survival factors for pulmonary plasma cells and thus are important regulators of the local Ab production in the allergic airway disease. PMID:19342646

  12. Role of upper airway ultrasound in airway management.

    PubMed

    Osman, Adi; Sum, Kok Meng

    2016-01-01

    Upper airway ultrasound is a valuable, non-invasive, simple, and portable point of care ultrasound (POCUS) for evaluation of airway management even in anatomy distorted by pathology or trauma. Ultrasound enables us to identify important sonoanatomy of the upper airway such as thyroid cartilage, epiglottis, cricoid cartilage, cricothyroid membrane, tracheal cartilages, and esophagus. Understanding this applied sonoanatomy facilitates clinician to use ultrasound in assessment of airway anatomy for difficult intubation, ETT and LMA placement and depth, assessment of airway size, ultrasound-guided invasive procedures such as percutaneous needle cricothyroidotomy and tracheostomy, prediction of postextubation stridor and left double-lumen bronchial tube size, and detecting upper airway pathologies. Widespread POCUS awareness, better technological advancements, portability, and availability of ultrasound in most critical areas facilitate upper airway ultrasound to become the potential first-line non-invasive airway assessment tool in the future. PMID:27529028

  13. Placenta growth factor augments airway hyperresponsiveness via leukotrienes and IL-13

    PubMed Central

    Eiymo Mwa Mpollo, Marthe-Sandrine; Brandt, Eric B.; Shanmukhappa, Shiva Kumar; Arumugam, Paritha I.; Tiwari, Swati; Loberg, Anastacia; Pillis, Devin; Rizvi, Tilat; Lindsey, Mark; Jonck, Bart; Carmeliet, Peter; Kalra, Vijay K.; Le Cras, Timothy D.; Ratner, Nancy; Wills-Karp, Marsha; Hershey, Gurjit K. Khurana; Malik, Punam

    2015-01-01

    Airway hyperresponsiveness (AHR) affects 55%–77% of children with sickle cell disease (SCD) and occurs even in the absence of asthma. While asthma increases SCD morbidity and mortality, the mechanisms underlying the high AHR prevalence in a hemoglobinopathy remain unknown. We hypothesized that placenta growth factor (PlGF), an erythroblast-secreted factor that is elevated in SCD, mediates AHR. In allergen-exposed mice, loss of Plgf dampened AHR, reduced inflammation and eosinophilia, and decreased expression of the Th2 cytokine IL-13 and the leukotriene-synthesizing enzymes 5-lipoxygenase and leukotriene-C4-synthase. Plgf–/– mice treated with leukotrienes phenocopied the WT response to allergen exposure; conversely, anti-PlGF Ab administration in WT animals blunted the AHR. Notably, Th2-mediated STAT6 activation further increased PlGF expression from lung epithelium, eosinophils, and macrophages, creating a PlGF/leukotriene/Th2-response positive feedback loop. Similarly, we found that the Th2 response in asthma patients is associated with increased expression of PlGF and its downstream genes in respiratory epithelial cells. In an SCD mouse model, we observed increased AHR and higher leukotriene levels that were abrogated by anti-PlGF Ab or the 5-lipoxygenase inhibitor zileuton. Overall, our findings indicate that PlGF exacerbates AHR and uniquely links the leukotriene and Th2 pathways in asthma. These data also suggest that zileuton and anti-PlGF Ab could be promising therapies to reduce pulmonary morbidity in SCD. PMID:26690703

  14. Placenta growth factor augments airway hyperresponsiveness via leukotrienes and IL-13.

    PubMed

    Eiymo Mwa Mpollo, Marthe-Sandrine; Brandt, Eric B; Shanmukhappa, Shiva Kumar; Arumugam, Paritha I; Tiwari, Swati; Loberg, Anastacia; Pillis, Devin; Rizvi, Tilat; Lindsey, Mark; Jonck, Bart; Carmeliet, Peter; Kalra, Vijay K; Le Cras, Timothy D; Ratner, Nancy; Wills-Karp, Marsha; Hershey, Gurjit K Khurana; Malik, Punam

    2016-02-01

    Airway hyperresponsiveness (AHR) affects 55%-77% of children with sickle cell disease (SCD) and occurs even in the absence of asthma. While asthma increases SCD morbidity and mortality, the mechanisms underlying the high AHR prevalence in a hemoglobinopathy remain unknown. We hypothesized that placenta growth factor (PlGF), an erythroblast-secreted factor that is elevated in SCD, mediates AHR. In allergen-exposed mice, loss of Plgf dampened AHR, reduced inflammation and eosinophilia, and decreased expression of the Th2 cytokine IL-13 and the leukotriene-synthesizing enzymes 5-lipoxygenase and leukotriene-C4-synthase. Plgf-/- mice treated with leukotrienes phenocopied the WT response to allergen exposure; conversely, anti-PlGF Ab administration in WT animals blunted the AHR. Notably, Th2-mediated STAT6 activation further increased PlGF expression from lung epithelium, eosinophils, and macrophages, creating a PlGF/leukotriene/Th2-response positive feedback loop. Similarly, we found that the Th2 response in asthma patients is associated with increased expression of PlGF and its downstream genes in respiratory epithelial cells. In an SCD mouse model, we observed increased AHR and higher leukotriene levels that were abrogated by anti-PlGF Ab or the 5-lipoxygenase inhibitor zileuton. Overall, our findings indicate that PlGF exacerbates AHR and uniquely links the leukotriene and Th2 pathways in asthma. These data also suggest that zileuton and anti-PlGF Ab could be promising therapies to reduce pulmonary morbidity in SCD. PMID:26690703

  15. A novel thiol compound, N-acetylcysteine amide, attenuates allergic airway disease by regulating activation of NF-kappaB and hypoxia-inducible factor-1alpha.

    PubMed

    Lee, Kyung Sun; Kim, So Ri; Park, Hee Sun; Park, Seoung Ju; Min, Kyung Hoon; Lee, Ka Young; Choe, Yeong Hun; Hong, Sang Hyun; Han, Hyo Jin; Lee, Young Rae; Kim, Jong Suk; Atlas, Daphne; Lee, Yong Chul

    2007-12-31

    Reactive oxygen species (ROS) play an important role in the pathogenesis of airway inflammation and hyperresponsiveness. Recent studies have demonstrated that antioxidants are able to reduce airway inflammation and hyperreactivity in animal models of allergic airway disease. A newly developed antioxidant, small molecular weight thiol compound, N-acetylcysteine amide (AD4) has been shown to increase cellular levels of glutathione and to attenuate oxidative stress related disorders such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis. However, the effects of AD4 on allergic airway disease such as asthma are unknown. We used ovalbumin (OVA)-inhaled mice to evaluate the role of AD4 in allergic airway disease. In this study with OVA-inhaled mice, the increased ROS generation, the increased levels of Th2 cytokines and VEGF, the increased vascular permeability, the increased mucus production, and the increased airway resistance in the lungs were significantly reduced by the administration of AD4. We also found that the administration of AD4 decreased the increases of the NF-kappaB and hypoxia-inducible factor-1alpha (HIF-1alpha) levels in nuclear protein extracts of lung tissues after OVA inhalation. These results suggest that AD4 attenuates airway inflammation and hyperresponsiveness by regulating activation of NF-kappaB and HIF-1alpha as well as reducing ROS generation in allergic airway disease. PMID:18160846

  16. Alveolar macrophage-derived vascular endothelial growth factor contributes to allergic airway inflammation in a mouse asthma model.

    PubMed

    Song, C; Ma, H; Yao, C; Tao, X; Gan, H

    2012-06-01

    Vascular endothelial growth factor (VEGF) is a potent proangiogenic factor that correlates with vascular permeability and remodelling in asthma. Recently, alveolar macrophages (AM) were shown to be an important source of VEGF during lung injury. Our previous studies demonstrated that AM are an important subset of macrophages in the initiation of asthmatic symptoms. Here, we further investigated whether AM-derived VEGF was required for allergic airway inflammation in asthma. In this study, we reported that the expression of VEGF in AM was significantly increased after allergen challenge. Depleting AM or neutralizing VEGF in alveolus prevented ovalbumin (OVA)-induced asthma-related inflammation by inhibiting the infiltration of inflammatory cells in the lung, reduced the level of the cytokines, IL-4, IL-5, and IL-13, in the bronchoalveolar lavage fluid (BALF) and decreased airway hyperresponsiveness (AHR). Moreover, the inhibition of miR-20b increased the protein level of VEGF in normal AM; conversely, increasing miR-20b in asthmatic AM resulted in decreased VEGF protein levels. These findings suggest that AM-derived VEGF is necessary for allergic airway inflammation in asthmatic mice and miR-20b negatively regulates this expression. PMID:22324377

  17. Bile Acids Repress Hypoxia-Inducible Factor 1 Signaling and Modulate the Airway Immune Response

    PubMed Central

    Legendre, Claire; Reen, F. Jerry; Woods, David F.; Mooij, Marlies J.; Adams, Claire

    2014-01-01

    Gastroesophageal reflux (GER) frequently occurs in patients with respiratory disease and is particularly prevalent in patients with cystic fibrosis. GER is a condition in which the duodenogastric contents of the stomach leak into the esophagus, in many cases resulting in aspiration into the respiratory tract. As such, the presence of GER-derived bile acids (BAs) has been confirmed in the bronchoalveolar lavage fluid and sputum of affected patients. We have recently shown that bile causes cystic fibrosis-associated bacterial pathogens to adopt a chronic lifestyle and may constitute a major host trigger underlying respiratory infection. The current study shows that BAs elicit a specific response in humans in which they repress hypoxia-inducible factor 1α (HIF-1α) protein, an emerging master regulator in response to infection and inflammation. HIF-1α repression was shown to occur through the 26S proteasome machinery via the prolyl hydroxylase domain (PHD) pathway. Further analysis of the downstream inflammatory response showed that HIF-1α repression by BAs can significantly modulate the immune response of airway epithelial cells, correlating with a decrease in interleukin-8 (IL-8) production, while IL-6 production was strongly increased. Importantly, the effects of BAs on cytokine production can also be more dominant than the bacterium-mediated effects. However, the effect of BAs on cytokine levels cannot be fully explained by their ability to repress HIF-1α, which is not surprising, given the complexity of the immune regulatory network. The suppression of HIF-1 signaling by bile acids may have a significant influence on the progression and outcome of respiratory disease, and the molecular mechanism underpinning this response warrants further investigation. PMID:24914220

  18. Increased transforming growth factor beta 1 expression mediates ozone-induced airway fibrosis in mice

    PubMed Central

    Katre, Ashwini; Ballinger, Carol; Akhter, Hasina; Fanucchi, Michelle; Kim, Dae-Kee; Postlethwait, Edward; Liu, Rui-Ming

    2013-01-01

    Ozone (O3), a commonly encountered environmental pollutant, has been shown to induce pulmonary fibrosis in different animal models; the underlying mechanism, however, remains elusive. To investigate the molecular mechanism underlying O3-induced pulmonary fibrosis, 6- to 8-week-old C57BL/6 male mice were exposed to a cyclic O3 exposure protocol consisting of 2 days of filtered air and 5 days of O3 exposure (0.5 ppm, 8 h/day) for 5 and 10 cycles with or without intraperitoneal injection of IN-1233, a specific inhibitor of the type 1 receptor of transforming growth factor beta (TGF-β), the most potent profibrogenic cytokine. The results showed that O3 exposure for 5 or 10 cycles increased the TGF-β protein level in the epithelial lining fluid (ELF), associated with an increase in the expression of plasminogen activator inhibitor 1 (PAI-1), a TGF-β-responsive gene that plays a critical role in the development of fibrosis under various pathological conditions. Cyclic O3 exposure also increased the deposition of collagens and alpha smooth muscle actin (α-SMA) in airway walls. However, these fibrotic changes were not overt until after 10 cycles of O3 exposure. Importantly, blockage of the TGF-β signaling pathway with IN-1233 suppressed O3-induced Smad2/3 phosphorylation, PAI-1 expression, as well as collagens and α-SMA deposition in the lung. Our data demonstrate for the first time that O3 exposure increases TGF-β expression and activates TGF-β signaling pathways, which mediates O3-induced lung fibrotic responses in vivo. PMID:21689010

  19. Comparison of analysis methods for airway quantification

    NASA Astrophysics Data System (ADS)

    Odry, Benjamin L.; Kiraly, Atilla P.; Novak, Carol L.; Naidich, David P.

    2012-03-01

    Diseased airways have been known for several years as a possible contributing factor to airflow limitation in Chronic Obstructive Pulmonary Diseases (COPD). Quantification of disease severity through the evaluation of airway dimensions - wall thickness and lumen diameter - has gained increased attention, thanks to the availability of multi-slice computed tomography (CT). Novel approaches have focused on automated methods of measurement as a faster and more objective means that the visual assessment routinely employed in the clinic. Since the Full-Width Half-Maximum (FWHM) method of airway measurement was introduced two decades ago [1], several new techniques for quantifying airways have been detailed in the literature, but no approach has truly become a standard for such analysis. Our own research group has presented two alternative approaches for determining airway dimensions, one involving a minimum path and the other active contours [2, 3]. With an increasing number of techniques dedicated to the same goal, we decided to take a step back and analyze the differences of these methods. We consequently put to the test our two methods of analysis and the FWHM approach. We first measured a set of 5 airways from a phantom of known dimensions. Then we compared measurements from the three methods to those of two independent readers, performed on 35 airways in 5 patients. We elaborate on the differences of each approach and suggest conclusions on which could be defined as the best one.

  20. Influence of genioglossus tonic activity on upper airway dynamics assessed by phrenic nerve stimulation.

    PubMed

    Sériès, F; Marc, I

    2002-01-01

    Upper airway (UA) dynamics can be evaluated during wakefulness by using electrical phrenic nerve stimulation (EPNS) applied at end-expiration during exclusive nasal breathing by dissociating twitch flow and phasic activation of UA muscles. This technique can be used to quantify the influence of nonphasic electromyographic (EMG) activity on UA dynamics. UA dynamics was characterized by using EPNS when increasing tonic EMG activity with CO(2) stimulation in six normal awake subjects. Instantaneous flow, esophageal and nasopharyngeal pressures, and genioglossal EMG activity were recorded during EPNS at baseline and during CO(2) ventilatory stimulation. The proportion of twitches presenting an inspiratory-flow limitation pattern decreased from 100% at baseline to 78.7 +/- 21.4% (P = 10(-4)) during CO(2) rebreathing. During CO(2) stimuli, maximal inspiratory twitch flow (VI(max)) of flow-limited twitches significantly rose, with the driving pressure at which flow limitation occurred being more negative. For the group as a whole, the increase in VI(max) and the decrease in pressure were significantly correlated with the rise in end-expiratory EMG activity. UA stability assessed by EPNS is dramatically modified during CO(2) ventilatory stimulation. Changes in tonic genioglossus EMG activity significantly contribute to the improvement in UA stability. PMID:11744686

  1. Chrysin attenuates allergic airway inflammation by modulating the transcription factors T-bet and GATA-3 in mice.

    PubMed

    Du, Qiang; Gu, Xiaoyan; Cai, Jiankang; Huang, Mao; Su, Mei

    2012-07-01

    Chrysin, a flavonoid obtained from various natural sources, has been reported to possess anti-inflammatory, antitumor, antioxidant and anti-allergic activities. However, its anti-inflammatory and immunoregulatory activities in asthma animal models are poorly understood. In the present study, we examined the effects of chrysin on airway inflammation and the possible mechanisms through which it acts in a murine model of allergic asthma. BALB/c mice sensitized and challenged to ovalbumin (OVA) were administered intragastrically with chrysin at a dose of 50 mg/kg daily. Chrysin significantly suppressed OVA-induced airway hyperresponsiveness (AHR) to acetylcholine chloride (Ach). Chrysin administration significantly inhibited the total inflammatory cell and eosinophil counts in bronchoalveolar lavage fluid (BALF) and total immunoglobulin E (IgE) levels in serum. Histological examination of lung tissue demonstrated that chrysin significantly attenuated allergen-induced lung eosinophilic inflammation and mucus-producing goblet cells in the airway. In addition, chrysin triggered a switch of the immune response to allergens towards a T-helper type 1 (Th1) profile by modulating the transcription factors T-bet and GATA-3 in allergic mice. These data suggest that chrysin exhibits anti-inflammatory and immunoregulatory properties and provides new insights into the immunopharmacological role of chrysin in terms of its effects in a murine model of asthma. PMID:22552848

  2. FACTORS THAT INFLUENCE THE RELATIVE POTENCY OF DIESEL EXHAUST PARTICLES AS ADJUVANTS IN ALLERGIC AIRWAY DISEASE

    EPA Science Inventory

    Description: Studies have shown that diesel exhaust particles (DEP) worsen respiratory diseases including allergic asthma. The adjuvant effects of DEP in the airways have been widely reported; however, the precise determinants and mechanisms of these effects are ill-defined. S...

  3. DIESEL EXHAUST ACTIVATES REDOX-SENSITIVE TRANSCRIPTION FACTORS AND KINASES IN HUMAN AIRWAYS

    EPA Science Inventory

    Diesel exhaust (DE) is a major component of airborne particulate matter. In previous studies we have described the acute inflammatory response of the human airway to inhaled DE. This was characterized by neutrophil, mast cell, and lymphocyte infiltration into the bronchial mucosa...

  4. Assessment of v-gel supraglottic airway device placement in cats performed by inexperienced veterinary students.

    PubMed

    Barletta, M; Kleine, S A; Quandt, J E

    2015-11-21

    Endotracheal intubation has been associated with several complications in cats. The v-gel supraglottic airway device (SGAD) has been developed to adapt to the unique oropharynx of the cat and to overcome these complications. Thirty-three cats were randomly assigned to receive an endotracheal tube (ETT group) or a v-gel SGAD (v-gel group) after induction of general anaesthesia. Third year veterinary students without previous clinical experience placed these devices under direct supervision of an anaesthesiologist. Amount of propofol, number of attempts, time required to secure the airway, leakage around the device, signs of upper airway discomfort and food consumption were compared between the two groups. The v-gel group required less propofol (P=0.03), less time (P<0.01) and fewer attempts (P<0.01) to secure the cats' airway. The incidence of leakage was lower for the v-gel group immediately after placement of the device (P<0.01) and 60 minutes after induction of general anaesthesia (P=0.04). Cats that received the v-gel SGAD presented a lower incidence of upper airway discomfort immediately after the device was removed (P=0.03) and recorded a higher food consumption score (P=0.03). The v-gel SGAD is a feasible way to secure the airway of healthy cats when performed by inexperienced personnel. PMID:26543177

  5. Airway tissue factor-dependent coagulation activity in response to sulfur mustard analog 2-chloroethyl ethyl sulfide

    PubMed Central

    Rancourt, Raymond C.; Veress, Livia A.; Guo, XiaoLing; Jones, Tara N.; Hendry-Hofer, Tara B.

    2012-01-01

    Acute lung injury is a principal cause of morbidity and mortality in response to mustard gas (SM) inhalation. Obstructive, fibrin-containing airway casts have recently been reported in a rat inhalation model employing the SM analog 2-chloroethyl ethyl sulfide (CEES). The present study was designed to identify the mechanism(s) causing activation of the coagulation cascade after CEES-induced airway injury. Here we report that CEES inhalation elevates tissue factor (TF) activity and numbers of detached epithelial cells present in lavage fluid (BALF) from rats after exposure (18 h). In vitro studies using 16HBE cells, or with rat BALF, indicated that detached epithelial cells could convert factor X (FX) to the active form FXa when incubated with factor VII and could elicit rapid clotting of plasma. In addition, immunocytochemical analysis demonstrated elevated cell surface (TF) expression on CEES-exposed 16HBE cells as a function of time. However, total cell TF expression did not increase. Since membrane surfaces bearing TF are important determinants of clot initiation, anticoagulants directed against these entities were tested for ability to limit plasma clotting or FX activation capacity of BALF or culture media. Addition of tifacogin, a TF pathway inhibitor, effectively blocked either activity, demonstrating that the procoagulant actions of CEES were TF pathway dependent. Lactadherin, a protein capable of competing with clotting factors for phospholipid-binding sites, was partially effective in limiting these procoagulant actions. These findings indicate that TF pathway inhibition could be an effective strategy to prevent airway obstruction after SM or CEES inhalation. PMID:21964405

  6. Nasal administration of interleukin-33 induces airways angiogenesis and expression of multiple angiogenic factors in a murine asthma surrogate.

    PubMed

    Shan, Shan; Li, Yan; Wang, Jingjing; Lv, Zhe; Yi, Dawei; Huang, Qiong; Corrigan, Chris J; Wang, Wei; Quangeng, Zhang; Ying, Sun

    2016-05-01

    The T-helper cell type 2-promoting cytokine interleukin-33 (IL-33) has been implicated in asthma pathogenesis. Angiogenesis is a feature of airways remodelling in asthma. We hypothesized that IL-33 induces airways angiogenesis and expression of angiogenic factors in an established murine surrogate of asthma. In the present study, BALB/c mice were subjected to serial intranasal challenge with IL-33 alone for up to 70 days. In parallel, ovalbumin (OVA) -sensitized mice were subjected to serial intranasal challenge with OVA or normal saline to serve as positive and negative controls, respectively. Immunohistochemical analysis of expression of von Willebrand factor and erythroblast transformation-specific-related gene, both blood vessel markers, and angiogenic factors angiogenin, insulin-like growth factor-1, endothelin-1, epidermal growth factor and amphiregulin was performed in lung sections ex vivo. An established in-house assay was used to test whether IL-33 was able to induce microvessel formation by human vascular endothelial cells. Results showed that serial intranasal challenge of mice with IL-33 or OVA resulted in proliferation of peribronchial von Willebrand factor-positive blood vessels to a degree closely related to the total expression of the angiogenic factors amphiregulin, angiogenin, endothelin-1, epidermal growth factor and insulin-like growth factor-1. IL-33 also induced microvessel formation by human endothelial cells in a concentration-dependent fashion in vitro. Our data are consistent with the hypothesis that IL-33 has the capacity to induce angiogenesis at least partly by increasing local expression of multiple angiogenic factors in an allergen-independent murine asthma surrogate, and consequently that IL-33 or its receptor is a potential novel molecular target for asthma therapy. PMID:27035894

  7. Serum Levels of Vascular Endothelial Growth Factor and Insulin-like Growth Factor Binding Protein-3 in Obstructive Sleep Apnea Patients: Effect of Continuous Positive Airway Pressure Treatment

    PubMed Central

    Archontogeorgis, Kostas; Nena, Evangelia; Papanas, Nikolaos; Xanthoudaki, Maria; Hatzizisi, Olga; Kyriazis, Georgios; Tsara, Venetia; Maltezos, Efstratios; Froudarakis, Marios; Steiropoulos, Paschalis

    2015-01-01

    Background and Aim: Hypoxia, a major feature of obstructive sleep apnea (OSA), modifies Vascular Endothelial Growth Factor (VEGF) and Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) levels, which contribute to atherogenesis and occurrence of cardiovascular (CV) events. We assessed and compared serum levels of VEGF and IGFBP-3 in newly diagnosed OSA patients and controls, to explore associations with anthropometric and sleep parameters and to study the effect of continuous positive airway pressure (CPAP) treatment on these levels. Materials and Methods: Serum levels of VEGF and IGFBP-3 were measured in 65 OSA patients and 31 age- and body mass index- matched controls. In OSA patients, measurements were repeated after 6 months of CPAP therapy. All participants were non-smokers, without any comorbidities or systemic medication use. Results: At baseline, serum VEGF levels in OSA patients were higher compared with controls (p<0.001), while IGFBP-3 levels were lower (1.41±0.56 vs. 1.61±0.38 μg/ml, p=0.039). VEGF levels correlated with apnea-hypopnea index (r=0.336, p=0.001) and oxygen desaturation index (r=0.282, p=0.007). After 6 months on CPAP treatment, VEGF levels decreased in OSA patients (p<0.001), while IGFBP-3 levels increased (p<0.001). Conclusion: In newly diagnosed OSA patients, serum levels of VEGF are elevated, while IGFBP-3 levels are low. After 6 months of CPAP treatment these levels change. These results may reflect an increased CV risk in untreated OSA patients, which is ameliorated after CPAP therapy. PMID:27006717

  8. Administration of Pigment Epithelium-Derived Factor Inhibits Airway Inflammation and Remodeling in Chronic OVA-Induced Mice via VEGF Suppression

    PubMed Central

    Zha, Wangjian; Su, Mei; Huang, Mao; Cai, Jiankang

    2016-01-01

    Purpose Pigment epithelium-derived factor (PEDF) is a recently discovered antiangiogenesis protein. PEDF possesses powerful anti-inflammatory, antioxidative, antiangiogenic, and antifibrosis properties. It has been reported that PEDF can regulate vascular endothelial growth factor (VEGF) expression. This study aimed to evaluate whether recombinant PEDF protein could attenuate allergic airway inflammation and airway remodeling via the negative regulation of VEGF using a murine model of chronic ovalbumin (OVA)-induced asthma and BEAS-2B human bronchial epithelial cells. Methods In an in vivo experiment, mice sensitized with OVA were chronically airway challenged with aerosolized 1% OVA solution for 8 weeks. Treated mice were given injections of recombinant PEDF protein (50 or 100 µg/kg body weight) via the tail vein. In an in vitro experiment, we investigated the effects of recombinant PEDF protein on VEGF release levels in BEAS-2B cells stimulated with IL-1β. Results Recombinant PEDF protein significantly inhibited eosinophilic airway inflammation, airway hyperresponsiveness, and airway remodeling, including goblet cell hyperplasia, subepithelial collagen deposition, and airway smooth muscle hypertrophy. In addition, recombinant PEDF protein suppressed the enhanced expression of VEGF protein in lung tissue and bronchoalveolar lavage fluid (BALF) in OVA-challenged chronically allergic mice. In the in vitro experiment, VEGF expression was increased after IL-1β stimulation. Pretreatment with 50 and 100 ng/mL of recombinant PEDF protein significantly attenuated the increase in VEGF release levels in a concentration-dependent manner in BEAS-2B cells stimulated by IL-1β. Conclusions These results suggest that recombinant PEDF protein may abolish the development of characteristic features of chronic allergic asthma via VEGF suppression, providing a potential treatment option for chronic airway inflammation diseases such as asthma. PMID:26739410

  9. Anthropometric Assessment of Neck Adipose Tissue and Airway Volume Using Multidetector Computed Tomography

    PubMed Central

    Maresky, Hillel S.; Sharfman, Zachary; Ziv-Baran, Tomer; Gomori, J.M.; Copel, Laurian; Tal, Sigal

    2015-01-01

    Abstract Neck adiposity tissue volume (NATV) accumulation is an indicator for metabolic syndrome and cardiovascular disease (CVD). Neck circumference is a poor measure of NATV, and a quantifier for this entity has not yet been established. To evaluate volumetric quantification by multidetector computed tomography (MDCT) as a reproducible anthropometric tool to measure NATV and airway volume (AWV). A total of 519 patients, including a subset of 70 random patients who underwent head and neck CT scanning in our hospital within 1 year (2013), were studied. Included patients were all those undergoing nonenhanced CT (NECT) or CT angiography (CTA). Neck cross-sectional areas (NCSA) were measured at 2 separate levels of the neck, and 3D postprocessing tissue reconstruction was performed, and NATV and AWVs were quantified volumetrically for all patients within the year. The average NCSA at the level of the soft palate and thyroid cartilage was 22,579 and 14,500 mm2, respectively. NATV when compared to the upper and lower levels of NCSA showed correlations of 0.64 and 0.79, respectively (P < 0.001). Interobserver analysis showed mean deviations of 0.46% and 0.32% for NATV and AWV, respectively. A strong correlation between NATV and body mass index (BMI) was found (r = 0.658, P < 0.001), and the top quartile of NATV:AWV patients (out of 519 patients) displayed a statistically significant mortality rate during 670 days of follow-up (d = 7.5%, P = 0.032). After adjustment for age and gender, the association between NATV:AWV and mortality was close to significant (P = 0.072). Volumetric quantification of NATV and AWV is a reproducible and prognostic anthropometric tool, as a high NATV:AWV demonstrated a significant risk factor for mortality; future research may further advance our understanding of this phenomenon. PMID:26559286

  10. NF-κB Activation Limits Airway Branching through Inhibition of Sp1-Mediated Fibroblast Growth Factor-10 Expression

    PubMed Central

    Benjamin, John T.; Carver, Billy J.; Plosa, Erin J.; Yamamoto, Yasutoshi; Miller, J. Davin; Liu, Jin-Hua; van der Meer, Riet; Blackwell, Timothy S.; Prince, Lawrence S.

    2015-01-01

    Bronchopulmonary dysplasia (BPD) is a frequent complication of preterm birth. This chronic lung disease results from arrested saccular airway development and is most common in infants exposed to inflammatory stimuli. In experimental models, inflammation inhibits expression of fibroblast growth factor-10 (FGF-10) and impairs epithelial–mesenchymal interactions during lung development; however, the mechanisms connecting inflammatory signaling with reduced growth factor expression are not yet understood. In this study we found that soluble inflammatory mediators present in tracheal fluid from preterm infants can prevent saccular airway branching. In addition, LPS treatment led to local production of mediators that inhibited airway branching and FGF-10 expression in LPS-resistant C.C3-Tlr4Lpsd/J fetal mouse lung explants. Both direct NF-κB activation and inflammatory cytokines (IL-1β and TNF-α) that activate NF-κB reduced FGF-10 expression, whereas chemokines that signal via other inflammatory pathways had no effect. Mutational analysis of the FGF-10 promoter failed to identify genetic elements required for direct NF-κB–mediated FGF-10 inhibition. Instead, NF-κB activation appeared to interfere with the normal stimulation of FGF-10 expression by Sp1. Chromatin immunoprecipitation and nuclear coimmunoprecipitation studies demonstrated that the RelA subunit of NF-κB and Sp1 physically interact at the FGF-10 promoter. These findings indicate that inflammatory signaling through NF-κB disrupts the normal expression of FGF-10 in fetal lung mesenchyme by interfering with the transcriptional machinery critical for lung morphogenesis. PMID:20861353

  11. Applications of mouse airway epithelial cell culture for asthma research.

    PubMed

    Horani, Amjad; Dickinson, John D; Brody, Steven L

    2013-01-01

    Primary airway epithelial cell culture provides a valuable tool for studying cell differentiation, cell-cell interactions, and the role of immune system factors in asthma pathogenesis. In this chapter, we discuss the application of mouse tracheal epithelial cell cultures for the study of asthma biology. A major advantage of this system is the ability to use airway epithelial cells from mice with defined genetic backgrounds. The in vitro proliferation and differentiation of mouse airway epithelial cells uses the air-liquid interface condition to generate well-differentiated epithelia with characteristics of native airways. Protocols are provided for manipulation of differentiation, induction of mucous cell metaplasia, genetic modification, and cell and pathogen coculture. Assays for the assessment of gene expression, responses of cells, and analysis of specific cell subpopulations within the airway epithelium are included. PMID:23943446

  12. A Subject-Specific Acoustic Model of the Upper Airway for Snoring Sounds Generation

    PubMed Central

    Saha, Shumit; Bradley, T. Douglas; Taheri, Mahsa; Moussavi, Zahra; Yadollahi, Azadeh

    2016-01-01

    Monitoring variations in the upper airway narrowing during sleep is invasive and expensive. Since snoring sounds are generated by air turbulence and vibrations of the upper airway due to its narrowing; snoring sounds may be used as a non-invasive technique to assess upper airway narrowing. Our goal was to develop a subject-specific acoustic model of the upper airway to investigate the impacts of upper airway anatomy, e.g. length, wall thickness and cross-sectional area, on snoring sounds features. To have a subject-specific model for snoring generation, we used measurements of the upper airway length, cross-sectional area and wall thickness from every individual to develop the model. To validate the proposed model, in 20 male individuals, intensity and resonant frequencies of modeled snoring sounds were compared with those measured from recorded snoring sounds during sleep. Based on both modeled and measured results, we found the only factor that may positively and significantly contribute to snoring intensity was narrowing in the upper airway. Furthermore, measured resonant frequencies of snoring were inversely correlated with the upper airway length, which is a risk factor for upper airway collapsibility. These results encourage the use of snoring sounds analysis to assess the upper airway anatomy during sleep. PMID:27210576

  13. A Subject-Specific Acoustic Model of the Upper Airway for Snoring Sounds Generation.

    PubMed

    Saha, Shumit; Bradley, T Douglas; Taheri, Mahsa; Moussavi, Zahra; Yadollahi, Azadeh

    2016-01-01

    Monitoring variations in the upper airway narrowing during sleep is invasive and expensive. Since snoring sounds are generated by air turbulence and vibrations of the upper airway due to its narrowing; snoring sounds may be used as a non-invasive technique to assess upper airway narrowing. Our goal was to develop a subject-specific acoustic model of the upper airway to investigate the impacts of upper airway anatomy, e.g. length, wall thickness and cross-sectional area, on snoring sounds features. To have a subject-specific model for snoring generation, we used measurements of the upper airway length, cross-sectional area and wall thickness from every individual to develop the model. To validate the proposed model, in 20 male individuals, intensity and resonant frequencies of modeled snoring sounds were compared with those measured from recorded snoring sounds during sleep. Based on both modeled and measured results, we found the only factor that may positively and significantly contribute to snoring intensity was narrowing in the upper airway. Furthermore, measured resonant frequencies of snoring were inversely correlated with the upper airway length, which is a risk factor for upper airway collapsibility. These results encourage the use of snoring sounds analysis to assess the upper airway anatomy during sleep. PMID:27210576

  14. Simvastatin Inhibits Airway Hyperreactivity

    PubMed Central

    Zeki, Amir A.; Franzi, Lisa; Last, Jerold; Kenyon, Nicholas J.

    2009-01-01

    Rationale: Statin use has been linked to improved lung health in asthma and chronic obstructive pulmonary disease. We hypothesize that statins inhibit allergic airway inflammation and reduce airway hyperreactivity via a mevalonate-dependent mechanism. Objectives: To determine whether simvastatin attenuates airway inflammation and improves lung physiology by mevalonate pathway inhibition. Methods: BALB/c mice were sensitized to ovalbumin over 4 weeks and exposed to 1% ovalbumin aerosol over 2 weeks. Simvastatin (40 mg/kg) or simvastatin plus mevalonate (20 mg/kg) was injected intraperitoneally before each ovalbumin exposure. Measurements and Main Results: Simvastatin reduced total lung lavage leukocytes, eosinophils, and macrophages (P < 0.05) in the ovalbumin-exposed mice. Cotreatment with mevalonate, in addition to simvastatin, reversed the antiinflammatory effects seen with simvastatin alone (P < 0.05). Lung lavage IL-4, IL-13, and tumor necrosis factor-α levels were all reduced by treatment with simvastatin (P < 0.05). Simvastatin treatment before methacholine bronchial challenge increased lung compliance and reduced airway hyperreactivity (P = 0.0001). Conclusions: Simvastatin attenuates allergic airway inflammation, inhibits key helper T cell type 1 and 2 chemokines, and improves lung physiology in a mouse model of asthma. The mevalonate pathway appears to modulate allergic airway inflammation, while the beneficial effects of simvastatin on lung compliance and airway hyperreactivity may be independent of the mevalonate pathway. Simvastatin and similar agents that modulate the mevalonate pathway may prove to be treatments for inflammatory airway diseases, such as asthma. PMID:19608720

  15. Interleukin-13 induces collagen type-1 expression through matrix metalloproteinase-2 and transforming growth factor-β1 in airway fibroblasts in asthma.

    PubMed

    Firszt, Rafael; Francisco, Dave; Church, Tony D; Thomas, Joseph M; Ingram, Jennifer L; Kraft, Monica

    2014-02-01

    Airway remodelling is a feature of asthma that contributes to loss of lung function. One of the central components of airway remodelling is subepithelial fibrosis. Interleukin (IL)-13 is a key T-helper 2 cytokine and is believed to be the central mediator of allergic asthma including remodelling, but the mechanism driving the latter has not been elucidated in human asthma. We hypothesised that IL-13 stimulates collagen type-1 production by the airway fibroblast in a matrix metalloproteinase (MMP)- and transforming growth factor (TGF)-β1-dependent manner in human asthma as compared to healthy controls. Fibroblasts were cultured from endobronchial biopsies in 14 subjects with mild asthma and 13 normal controls that underwent bronchoscopy. Airway fibroblasts were treated with various mediators including IL-13 and specific MMP-inhibitors. IL-13 significantly stimulated collagen type-1 production in asthma compared to normal controls. Inhibitors of MMP-2 significantly attenuated collagen production in asthma but had no effect in normal controls. IL-13 significantly increased total and active forms of TGF-β1, and this activation was blocked using an MMP-2 inhibitor. IL-13 activated endogenous MMP-2 in asthma patients as compared to normal controls. In an ex vivo model, IL-13 potentiates airway remodelling through a mechanism involving TGF-β1 and MMP-2. These effects provide insights into the mechanism involved in IL-13-directed airway remodelling in asthma. PMID:23682108

  16. Human factors and risk assessment

    SciTech Connect

    Al-Minhali, A.

    1996-11-01

    A case study was presented in the 1994 Abu Dhabi International Exhibition and Conference (ADIPEC, 94) which discussed the importance of investigating human factors in the design of a high integrity protection system (HIPS) to be installed on an offshore high pressure gas platform, (SPE reference ADSPE 80). This paper will follow up on the design changes, installation and operation of the HIPS with emphasis on practical implications as a result of improper integration of human factors in the system reliability and risk assessment studies.

  17. Randomized placebo controlled assessment of airway inflammation due to racemic albuterol and levalbuterol via exhaled nitric oxide testing

    PubMed Central

    Freiler, John F; Arora, Rajiv; Kelley, Thomas C; Hagan, Larry; Allan, Patrick F

    2006-01-01

    Study Objectives The S-stereoisomer found in racemic albuterol may have associated proinflammatory properties. We tested the hypothesis that airway inflammation as assessed by exhaled nitric oxide is no different in patients with COPD when using racemic albuterol relative to levalbuterol or placebo. Measurements Twelve mild to moderate COPD patients were assigned to five days each of nebulized racemic albuterol, levalbuterol, and saline placebo. Before and after each course of treatment, airway inflammation was assessed via exhaled nitric oxide breath testing. Secondary functional outcomes that were measured included spirometry, a functional assessment utilizing a six-minute walk, and symptoms score using the University of California, San Diego Shortness of Breath Questionnaire. Results There was no statistically significant difference in pre and post FeNO levels within and between treatment groups (p = 0.121). There were also no significant differences within or between treatment groups for the secondary outcome measurements of FEV1 (p = 0.913), functional assessment utilizing a six-minute walk (p = 0.838) and the symptom scores using Shortness of Breath Questionnaire (p = 0.500). Conclusion We found no difference in mild to moderate COPD patients treated with racemic albuterol, levalbuterol or placebo for measurement of exhaled nitric oxide or the secondary outcomes that were measured. PMID:18044102

  18. Surgical Airway

    PubMed Central

    Patel, Sapna A; Meyer, Tanya K

    2014-01-01

    Close to 3% of all intubation attempts are considered difficult airways, for which a plan for a surgical airway should be considered. Our article provides an overview of the different types of surgical airways. This article provides a comprehensive review of the main types of surgical airways, relevant anatomy, necessary equipment, indications and contraindications, preparation and positioning, technique, complications, and tips for management. It is important to remember that the placement of a surgical airway is a lifesaving procedure and should be considered in any setting when one “cannot intubate, cannot ventilate”. PMID:24741501

  19. Nuclear factor-κB mediates the phenotype switching of airway smooth muscle cells in a murine asthma model

    PubMed Central

    Qiu, Chen; Zhang, Jian; Su, Meiping; Fan, Xiujun

    2015-01-01

    Airway smooth muscle cells (ASMCs) phenotype modulation, characterized by reversible switching between contractile and proliferative phenotypes, is considered to contribute to airway proliferative diseases such as allergic asthma. Nuclear Factor-κB (NF-κB) has been reported as a key regulator for the occurrence and development of asthma. However, little is known regarding its role in ASM cell phenotypic modulation. To elucidate the role of NF-κB in regulating ASM cells phenotypic modulation, we investigated the effects of NF-κB on ASM cells contractile marker protein expression, and its impact on proliferation and apoptosis. We found that chronic asthma increased the activation of NF-κB in the primary murine ASM cells with a concomitant marked decrease in the expression of contractile phenotypic marker protein including smooth muscle alpha-actin (α-SMA). Additionally, we used the normal ASM cells under different processing to build the phenotype switching when we found the activation of NF-κB. Meanwhile, the expression of α-SMA in asthma was significantly increased by the NF-κB blocker. NF-κB blocker also suppressed asthma mouse ASM cell proliferation and promoted apoptosis. These findings highlight a novel role for the NF-κB in murine ASM cell phenotypic modulation and provide a potential target for therapeutic intervention for asthma. PMID:26722396

  20. Quantitative airway assessment on computed tomography in patients with alpha1-antitrypsin deficiency.

    PubMed

    Yamashiro, Tsuneo; Matsuoka, Shin; Estépar, Raúl San José; Diaz, Alejandro; Newell, John D; Sandhaus, Robert A; Mergo, Patricia J; Brantly, Mark L; Murayama, Sadayuki; Reilly, John J; Hatabu, Hiroto; Silverman, Edwin K; Washko, George R

    2009-12-01

    The relationship between quantitative airway measurements on computed tomography (CT) and airflow limitation in individuals with severe alpha (1)-antitrypsin deficiency (AATD) is undefined. Thus, we planned to clarify the relationship between CT-based airway indices and airflow limitation in AATD. 52 patients with AATD underwent chest CT and pre-bronchodilator spirometry at three institutions. In the right upper (RUL) and lower (RLL) lobes, wall area percent (WA%) and luminal area (Ai) were measured in the third, fourth, and fifth generations of the bronchi. The severity of emphysema was also calculated in each lobe and expressed as low attenuation area percent (LAA%). Correlations between obtained measurements and FEV(1)% predicted (FEV(1)%P) were evaluated by the Spearman rank correlation test. In RUL, WA% of all generations was significantly correlated with FEV(1)%P (3rd, R = -0.33, p = 0.02; 4th, R = -0.39, p = 0.004; 5th, R = -0.57, p < 0.001; respectively). Ai also showed significant correlations (3rd, R = 0.32, p = 0.02; 4th, R = 0.34, p = 0.01; 5th, R = 0.56, p < 0.001; respectively). Measured correlation coefficients improved when the airway progressed distally from the third to fifth generations. LAA% also correlated with FEV(1)%P (R = -0.51, p < 0.001). In RLL, WA% showed weak correlations with FEV(1)%P in all generations (3rd, R = -0.34, p = 0.01; 4th, R = -0.30, p = 0.03; 5th, R = -0.31, p = 0.03; respectively). Only Ai from the fifth generation significantly correlated with FEV(1)%P in this lobe (R = 0.34, p = 0.01). LAA% strongly correlated with FEV(1)%P (R = -0.71, p < 0.001). We conclude therefore that quantitative airway measurements are significantly correlated with airflow limitation in AATD, particularly in the distal airways of RUL. Emphysema of the lower lung is the predominant component; however, airway disease also has a significant impact on airflow limitation in AATD. PMID:19938971

  1. Meteorological conditions along airways

    NASA Technical Reports Server (NTRS)

    Gregg, W R

    1927-01-01

    This report is an attempt to show the kind of meteorological information that is needed, and is in part available, for the purpose of determining operating conditions along airways. In general, the same factors affect these operating conditions along all airways though in varying degree, depending upon their topographic, geographic, and other characteristics; but in order to bring out as clearly as possible the nature of the data available, a specific example is taken, that of the Chicago-Dallas airway on which regular flying begins this year (1926).

  2. Specificity and sensitivity of respiratory impedance in assessing reversibility of airway obstruction in children.

    PubMed

    Mazurek, H K; Marchal, F; Derelle, J; Hatahet, R; Moneret-Vautrin, D; Monin, P

    1995-04-01

    Flow in the upper airway wall induces significant error in estimating respiratory impedance by the standard forced oscillation technique in subjects with airway obstruction and may be minimized by oscillating pressure around the subject's head (head generator technique). The aim of this study was to determine whether the latter improves the power of forced oscillations in detecting airway response to bronchodilators in children. Seventy-five children with airway obstruction were studied (ages 5.5 to 15 years old). Fifty-three had asthma and 22, cystic fibrosis. A bronchodilator was administered, and the percent changes in respiratory resistance at 10 Hz (Rrs10), 20 Hz (Rrs20), respiratory compliance (Crs), and resonant frequency (fn) with standard and head generator were compared with the corresponding change in FEV1. The response was positive in 38 (delta % FEV1 > or = 15%) and negative in 37 patients. Data on Rrs10, Crs, and fn could not be obtained in 7, 8, and 4 subjects, respectively, for technical reasons. The delta % Rrs20 was not different between head and standard generator in nonresponders (mean +/- SEM: -19.0 +/- 4.5, vs -11.8 +/- 3.1%), but significantly larger with head than standard generator in responders (-54.1 +/- 3.0 vs -26.5 +/- 2.4%; p < 0.001). The optimal decision level determined by Receiver Operation Characteristic analysis showed that, compared with the standard method, the head generator improved the specificity of Rrs20 (78 vs 65%) with no change in sensitivity (76% for both). Resonant frequency had larger sensitivity with standard than with head generator (91 vs 53%) but slightly lower specificity (70 vs 78%). Finally, delta %Crs was more specific (72 vs 67%) and more sensitive (68 vs 52%) with standard than with head generator. The overall incidence of false results was lower with the head generator than with the standard generator for resistance and lower with the standard generator than with the head generator for fn and compliance

  3. Extracellular acidification induces connective tissue growth factor production through proton-sensing receptor OGR1 in human airway smooth muscle cells

    SciTech Connect

    Matsuzaki, Shinichi; Ishizuka, Tamotsu; Yamada, Hidenori; Kamide, Yosuke; Hisada, Takeshi; Ichimonji, Isao; Aoki, Haruka; Yatomi, Masakiyo; Komachi, Mayumi; Tsurumaki, Hiroaki; Ono, Akihiro; Koga, Yasuhiko; Dobashi, Kunio; Mogi, Chihiro; Sato, Koichi; Tomura, Hideaki; Mori, Masatomo; Okajima, Fumikazu

    2011-10-07

    Highlights: {yields} The involvement of extracellular acidification in airway remodeling was investigated. {yields} Extracellular acidification alone induced CTGF production in human ASMCs. {yields} Extracellular acidification enhanced TGF-{beta}-induced CTGF production in human ASMCs. {yields} Proton-sensing receptor OGR1 was involved in acidic pH-stimulated CTGF production. {yields} OGR1 may play an important role in airway remodeling in asthma. -- Abstract: Asthma is characterized by airway inflammation, hyper-responsiveness and remodeling. Extracellular acidification is known to be associated with severe asthma; however, the role of extracellular acidification in airway remodeling remains elusive. In the present study, the effects of acidification on the expression of connective tissue growth factor (CTGF), a critical factor involved in the formation of extracellular matrix proteins and hence airway remodeling, were examined in human airway smooth muscle cells (ASMCs). Acidic pH alone induced a substantial production of CTGF, and enhanced transforming growth factor (TGF)-{beta}-induced CTGF mRNA and protein expression. The extracellular acidic pH-induced effects were inhibited by knockdown of a proton-sensing ovarian cancer G-protein-coupled receptor (OGR1) with its specific small interfering RNA and by addition of the G{sub q/11} protein-specific inhibitor, YM-254890, or the inositol-1,4,5-trisphosphate (IP{sub 3}) receptor antagonist, 2-APB. In conclusion, extracellular acidification induces CTGF production through the OGR1/G{sub q/11} protein and inositol-1,4,5-trisphosphate-induced Ca{sup 2+} mobilization in human ASMCs.

  4. Precursor B Cells Increase in the Lung during Airway Allergic Inflammation: A Role for B Cell-Activating Factor

    PubMed Central

    Malmhäll, Carina; Rådinger, Madeleine; Ramos-Ramirez, Patricia; Lu, You; Deák, Tünde; Semitekolou, Maria; Gaga, Mina; Sjöstrand, Margareta; Lötvall, Jan; Bossios, Apostolos

    2016-01-01

    Background B cells, key cells in allergic inflammation, differentiate in the bone marrow and their precursors include pro-B, pre-B and immature B cells. Eosinophil progenitor cells increase in the lung after allergen exposure. However, the existence and possible role of B cell precursors in the lung during allergic inflammation remains elusive. Methods A BALB/c mouse model of allergic airway inflammation was utilized to perform phenotypic and quantification analyses of pro-B and pre-B cells in the lung by flow cytometry. B cell maturation factors IL-7 and B cell-activating factor (BAFF) and their receptors (CD127 and BAFFR, BCMA, TACI, respectively) were also evaluated in the lung and serum. The effect of anti-BAFF treatment was investigated both in vivo (i.p. administration of BAFF-R-Ig fusion protein) and in vitro (colony forming cell assay). Finally, BAFF levels were examined in the bronchoalveolar lavage (BAL) of asthmatic patients and healthy controls. Results Precursor pro and pre-B cells increase in the lung after allergen exposure, proliferate in the lung tissue in vivo, express markers of chemotaxis (CCR10 and CXCR4) and co-stimulation (CD40, CD86) and are resistant to apoptosis (Bax). Precursor B cells express receptors for BAFF at baseline, while after allergen challenge both their ligand BAFF and the BCMA receptor expression increases in B cell precursors. Blocking BAFFR in the lung in vivo decreases eosinophils and proliferating precursor B cells. Blocking BAFFR in bone marrow cultures in vitro reduces pre-B colony formation units. BAFF is increased in the BAL of severe asthmatics. Conclusion Our data support the concept of a BAFF-mediated role for B cell precursors in allergic airway inflammation. PMID:27513955

  5. MATRIX METALLOPROTEINS (MMP)-MEDIATED PHOSPHORYLATION OF THE EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) IN HUMAN AIRWAY EPITHELIAL CELLS (HAEC) EXPOSED TO ZINC (ZN)

    EPA Science Inventory

    Matrix Metalloproteinase (MMP)-Mediated Phosphorylation of The Epidermal Growth Factor Receptor (EGFR) in Human Airway Epithelial Cells (HAEC) Exposed to Zinc (Zn)
    Weidong Wu, James M. Samet, Robert Silbajoris, Lisa A. Dailey, Lee M. Graves, and Philip A. Bromberg
    Center fo...

  6. Airway wall thickness assessment: a new functionality in virtual bronchoscopy investigation

    NASA Astrophysics Data System (ADS)

    Saragaglia, A.; Fetita, C.; Brillet, P. Y.; Prêteux, F.; Grenier, P. A.

    2007-03-01

    While classic virtual bronchoscopy offers visualization facilities for investigating the shape of the inner airway wall surface, it provides no information regarding the local thickness of the wall. Such information may be crucial for evaluating the severity of remodeling of the bronchial wall in asthma and to guide bronchial biopsies for staging of lung cancers. This paper develops a new functionality with the virtual bronchoscopy, allowing to estimate and map the information of the bronchus wall thickness on the lumen wall surface, and to display it as coded colors during endoluminal navigation. The local bronchus wall thickness estimation relies on a new automated 3D segmentation approach using strong 3D morphological filtering and model-fitting. Such an approach reconstructs the inner/outer airway wall surfaces from multi-detector CT data as follows. First, the airway lumen is segmented and its surface geometry reconstructed using either a restricted Delaunay or a Marching Cubes based triangulation approach. The lumen mesh is then locally deformed in the surface normal direction under specific force constraints which stabilize the model evolution at the level of the outer bronchus wall surface. The developed segmentation approach was validated with respect to both 3D mathematicallysimulated image phantoms of bronchus-vessel subdivisions and to state-of-the-art cross-section area estimation techniques when applied to clinical data. The investigation in virtual bronchoscopy mode is further enhanced by encoding the local wall thickness at each vertex of the lumen surface mesh and displaying it during navigation, according to a specific color map.

  7. Clinical characteristics of adult asthma associated with small airway dysfunction.

    PubMed

    Kjellberg, S; Houltz, B K; Zetterström, O; Robinson, P D; Gustafsson, Per M

    2016-08-01

    Suboptimal asthma control is common despite modern asthma therapy. The degree of peripheral airway involvement remains unclear and poor medication delivery to these regions might be a contributing reason for this failure in obtaining adequate symptom control. A cohort of 196 adults (median (range) age 44 (18-61) years, 109 females, 54 ex-smokers, six current smokers) with physician-diagnosed asthma were recruited from primary care. Subjects were characterized clinically by interviews, questionnaires, skin prick tests (SPT) and blood eosinophil counts. Lung function was assessed by spirometry, impulse oscillometry (IOS) and nitrogen multiple breath washout (N2 MBW). IOS assessed peripheral airway resistance (FDR, frequency dependence of resistance). N2 MBW assessed global ventilation inhomogeneity (LCI, lung clearance index), specific indices of peripheral airway function (Scond × VT and Sacin × VT; VT, tidal volume), and inter-regional inhomogeneity (specific ventilation ratio). Never-smoking healthy cohorts of 158 and 400 adult subjects provided local reference values for IOS and N2 MBW variables, respectively. Peripheral airway dysfunction was detected in 31% (FDR or specific ventilation ratio) to 47% (Scond x VT) of subjects. Risk factors for peripheral airway dysfunction were identified. Among subjects with low FEV1 and either positive smoking history and/or blood eosinophilia (>4.0%), 63% had abnormality across all peripheral airway outcomes, whilst only one subject was completely normal. Abnormal peripheral airway function was present in a large proportion of adult asthmatics at baseline. Reduced FEV1, a positive smoking history, and/or blood eosinophilia identified "a small airway asthma subtype" that might benefit from peripheral airway targeted therapy. PMID:27492518

  8. Vasoactive peptides upregulate mRNA expression and secretion of vascular endothelial growth factor in human airway smooth muscle cells.

    PubMed

    Alagappan, Vijay K T; Willems-Widyastuti, Anna; Seynhaeve, Ann L B; Garrelds, Ingrid M; ten Hagen, Timo L M; Saxena, Pramod R; Sharma, Hari S

    2007-01-01

    Airway remodeling and associated angiogenesis are documented features of asthma, of which the molecular mechanisms are not fully understood. Angiotensin (ANG)II and endothelin (ET)-1 are potent vasoconstricting circulatory hormones implicated in asthma. We investigated the effects of ANG II and ET-1 on human airway smooth muscle (ASM) cells proliferation and growth and examined the mRNA expression and release of the angiogenic peptide, vascular endothelial growth factor (VEGF). Serum deprived (48 h) human ASM cells were incubated with ANG II (100 nM) or ET-1 (10 nM) for 30 min, 1, 2, 4, 8, 16, and 24 h and the endogenous synthesis of VEGF was examined in relation to control cells receiving serum free culture medium. ET-1 induced time dependent DNA biosynthesis as determined by [3H]-thymidine incorporation assay. Using northern blot hybridization, we detected two mRNA species of 3.9 and 1.7 kb encoding VEGF in the cultured smooth muscle cells. Both ANG II and ET-1 induced the mRNA expression (two- to threefold) and secretion (1.8- to 2.8-fold) of VEGF reaching maximal levels between 4-8 h of incubation. Induced expression and release of VEGF declined after 8 h of ANG II incubation while levels remained elevated in the case of ET-1. The conditioned medium derived from ET-1-treated ASM cells induced [3H]-thymidine incorporation and cell number in porcine pulmonary artery endothelial as well as human umbilical vein endothelial cells. Moreover, the VEGF tyrosine kinase receptor inhibitor blocked the conditioned medium induced mitogenesis in endothelial cells. Our results suggest a potential role for ANG II and ET-1 in ASM cell growth and upregulation of VEGF that may participate in endothelial cell proliferation via paracrine mechanisms and thus causing pathological angiogenesis and vascular remodelling seen during asthma. PMID:17406064

  9. Roles of lipoxin A4 receptor activation and anti-interleukin-1β antibody on the toll-like receptor 2/mycloid differentiation factor 88/nuclear factor-κB pathway in airway inflammation induced by ovalbumin

    PubMed Central

    KONG, XIA; WU, SHENG-HUA; ZHANG, LI; CHEN, XIAO-QING

    2015-01-01

    Previous studies investigating the role of toll-like receptors (TLRs) in asthma have been inconclusive. It has remained elusive whether the toll-like receptors (TLR2)/mycloid differentiation factor 88 (MyD88)/nuclear factor (NF)-κB signaling pathway is involved in lipoxin A4 (LXA4)-induced protection against asthma. Therefore, the present study investigated whether ovalbumin (OVA)-induced airway inflammation is mediated by upregulation of the TLR2/MyD88/NF-κB signaling pathway, and whether it proceeds via the inhibition of the activation of the LXA4 receptor and anti-interleukin (IL)-1β antibodies. Mice with airway inflammation induced by OVA administration were treated with or without a LXA4 receptor agonist, BML-111 and anti-IL-1β antibody. Serum levels of IL-1β, IL-4, IL-8 and interferon-γ (IFN-γ) were assessed, and levels of IL-1β, IL-4, IL-8 and OVA-immunoglobulin (Ig)E, as well as leukocyte counts in the bronchoalveolar lavage fluid (BALF) were measured. Pathological features and expression of TLR2, MyD88 and NF-κB in the lungs were analyzed. Expression of TLR2 and MyD88, and activation of NF-κB in leukocytes as well as levels of IL-4, IL-6 and IL-8 released from leukocytes exposed to IL-1β were assessed. OVA treatment increased the levels of IL-1β, IL-4 and IL-8 in the serum and BLAF, the number of leukocytes and the levels of OVA-IgE in the BALF, the expression of TLR2 and MyD88, and the activation of NF-κB in the lung. These increments induced by OVA were inhibited by treatment with BML-111 and anti-IL-1β antibodies. Treatment of the leukocytes with BML-111 or TLR2 antibody, or MyD88 or NF-κB inhibitor, all blocked the IL-1β-triggered production of IL-4, IL-6 and IL-8 and activation of NF-κB. Treatment of the leukocytes with BML-111 or TLR2 antibody suppressed IL-1β-induced TLR2 and MyD88 expression. The present study therefore suggested that OVA-induced airway inflammation is mediated by the TLR2/MyD88/NF-κB pathway. IL-1β has a

  10. Factors associated with major complications in the short-term postoperative period in dogs undergoing surgery for brachycephalic airway syndrome.

    PubMed

    Ree, Jennifer J; Milovancev, Milan; MacIntyre, Laura A; Townsend, Katy L

    2016-09-01

    Surgical correction of brachycephalic airway syndrome (BAS) in dogs has been reported to result in low complication rates and good long-term outcomes. Previous reports have not identified risk factors for the development of complications following BAS surgery. This retrospective study evaluated a wide variety of patient- and procedure-related, pre-operative, intra-operative, and post-operative factors for an association with the development of major postoperative complications in the short-term period following BAS surgery. The overall major complication rate, including death or euthanasia, was 4/55 (7%) dogs. Temporary tracheostomy was the only major surgical complication identified (n = 3). Multiple logistic regression identified postoperative radiographic evidence of pneumonia as associated with the development of any major complication overall, requirement of a temporary tracheostomy postoperatively, and death or euthanasia, within the short-term postoperative period. Future prospective studies should evaluate specific risk factors for an association with major complications following BAS surgery in dogs to improve patient outcomes. PMID:27587891

  11. Adherence to Airway Clearance Therapy in Pediatric Cystic Fibrosis: Socioeconomic Factors and Respiratory Outcomes

    PubMed Central

    Oates, Gabriela R.; Stepanikova, Irena; Gamble, Stephanie; Gutierrez, Hector H.; Harris, William T.

    2016-01-01

    Summary Objectives The evidence linking socioeconomic status (SES) and adherence in cystic fibrosis (CF) is inconclusive and focused on medication uptake. We examined associations between SES, adherence to airway clearance therapy (ACT), and CF respiratory outcomes. Study Design Socioeconomic, clinical, and adherence data of CF patients (N = 110) at a single CF Center were evaluated in this cross-sectional observational study. SES was operationalized as maternal and paternal education and household income. Adherence to ACT was measured with utilization data from the high-frequency chest wall oscillation (HFCWO) device over 4–6 weeks. Statistical modeling was used to test three hypotheses: (H1) Higher SES is associated with higher ACT adherence; (H2) Higher SES is associated with better respiratory outcomes; and (H3) ACT adherence mediates the relationship between SES and respiratory outcomes. Results In multinomial logistic regression, maternal college education, annual income >$50,000, and more adults in the household were independently related to better adherence (P < 0.05). Paternal college education, income >$100,000, and lack of exposure to smoking were independently related to higher lung function (P < 0.05). Current adherence to ACT with HFCWO was not associated with lung function over 12 months. Conclusions SES is associated both with ACT adherence and respiratory outcomes in pediatric CF patients. However, the link between SES and respiratory outcomes in this study was not mediated by adherence to ACT with HFCWO. These data emphasize the importance of socioeconomic resources and household environment for CF health. Family socio-demographic profiles can help identify patients at increased risk for ACT nonadherence. PMID:26436321

  12. Corrections in dose assessment of 99mTc radiolabeled aerosol particles targeted to central human airways using planar gamma camera imaging.

    PubMed

    Möller, Winfried; Felten, Kathrin; Meyer, Gabriele; Meyer, Peter; Seitz, Jürgen; Kreyling, Wolfgang G

    2009-03-01

    The dose of inhaled radiolabeled aerosols is usually assessed using gamma (GC) camera imaging. Because of the complex and inhomogeneous structure of the lung, consisting of soft tissue, the thoracic skeleton, blood vessels, and air spaces, proper attenuation correction coefficients are difficult to evaluate and the estimated doses bear high uncertainty. One hundred milliliters of aerosol boli composed of 100 nm diameter (99m)Tc radiolabeled carbon particles (Technegas) were targeted either to the airways (AW) or to 800-mL volumetric lung depth (alveoli, AL) in 11 healthy volunteers. In addition, 750-mL full breaths (FB) of aerosol were inhaled to a 800-mL lung depth. The deposited dose was measured by collecting aerosol from inhaled and exhaled air stream on filters, which were analyzed for radioactivity. Lung imaging was performed using a planar GC (posterior). Ratios of GC counts to deposited dose (GC/DD) were similar after FB and AL administration, but twofold lower after AW administration (p < 0.01). Associated attenuation correction factors (ACF) were 2.5 +/- 0.5 (FB), 2.2 +/- 0.4 (AL), and 5.5 +/- 1.6 (AW, p < 0.01). Both GC/DD and ACF were highly correlated to the aerosol distribution index (central to peripheral ratio, C/P). After shallow bolus administration there was a negative correlation between body mass index and GC/DD. Inhalation of radioaerosols used in medical diagnosis and therapy in combination with high central airway deposition results in an underestimation of the deposited dose based on planar GC imaging. The aerosol distribution index C/P may provide one suitable indicator for corrections, which should be confirmed in future studies by individual attenuation analysis based on radiotracer transmission measurements. PMID:18844481

  13. Dual Pili Post-translational Modifications Synergize to Mediate Meningococcal Adherence to Platelet Activating Factor Receptor on Human Airway Cells

    PubMed Central

    Schulz, Benjamin L.; Power, Peter M.; Swords, W. Edward; Weiser, Jeffery N.; Apicella, Michael A.; Edwards, Jennifer L.; Jennings, Michael P.

    2013-01-01

    Pili of pathogenic Neisseria are major virulence factors associated with adhesion, twitching motility, auto-aggregation, and DNA transformation. Pili of N. meningitidis are subject to several different post-translational modifications. Among these pilin modifications, the presence of phosphorylcholine (ChoP) and a glycan on the pilin protein are phase-variable (subject to high frequency, reversible on/off switching of expression). In this study we report the location of two ChoP modifications on the C-terminus of N. meningitidis pilin. We show that the surface accessibility of ChoP on pili is affected by phase variable changes to the structure of the pilin-linked glycan. We identify for the first time that the platelet activating factor receptor (PAFr) is a key, early event receptor for meningococcal adherence to human bronchial epithelial cells and tissue, and that synergy between the pilin-linked glycan and ChoP post-translational modifications is required for pili to optimally engage PAFr to mediate adherence to human airway cells. PMID:23696740

  14. Virulence Factors of Pseudomonas aeruginosa Induce Both the Unfolded Protein and Integrated Stress Responses in Airway Epithelial Cells.

    PubMed

    van 't Wout, Emily F A; van Schadewijk, Annemarie; van Boxtel, Ria; Dalton, Lucy E; Clarke, Hanna J; Tommassen, Jan; Marciniak, Stefan J; Hiemstra, Pieter S

    2015-06-01

    Pseudomonas aeruginosa infection can be disastrous in chronic lung diseases such as cystic fibrosis and chronic obstructive pulmonary disease. Its toxic effects are largely mediated by secreted virulence factors including pyocyanin, elastase and alkaline protease (AprA). Efficient functioning of the endoplasmic reticulum (ER) is crucial for cell survival and appropriate immune responses, while an excess of unfolded proteins within the ER leads to "ER stress" and activation of the "unfolded protein response" (UPR). Bacterial infection and Toll-like receptor activation trigger the UPR most likely due to the increased demand for protein folding of inflammatory mediators. In this study, we show that cell-free conditioned medium of the PAO1 strain of P. aeruginosa, containing secreted virulence factors, induces ER stress in primary bronchial epithelial cells as evidenced by splicing of XBP1 mRNA and induction of CHOP, GRP78 and GADD34 expression. Most aspects of the ER stress response were dependent on TAK1 and p38 MAPK, except for the induction of GADD34 mRNA. Using various mutant strains and purified virulence factors, we identified pyocyanin and AprA as inducers of ER stress. However, the induction of GADD34 was mediated by an ER stress-independent integrated stress response (ISR) which was at least partly dependent on the iron-sensing eIF2α kinase HRI. Our data strongly suggest that this increased GADD34 expression served to protect against Pseudomonas-induced, iron-sensitive cell cytotoxicity. In summary, virulence factors from P. aeruginosa induce ER stress in airway epithelial cells and also trigger the ISR to improve cell survival of the host. PMID:26083346

  15. Eosinophil accumulation in pulmonary airways of guinea-pigs induced by exposure to an aerosol of platelet-activating factor: effect of anti-asthma drugs.

    PubMed Central

    Sanjar, S.; Aoki, S.; Boubekeur, K.; Chapman, I. D.; Smith, D.; Kings, M. A.; Morley, J.

    1990-01-01

    1. Exposure of guinea-pigs to aerosols of platelet activating factor (PAF) (0.01 to 100 micrograms ml-1) induced a dose-dependent increased incidence of eosinophils in bronchoalveolar lavage fluid (BAL) at 48 h. Total leucocyte numbers and the percentages of lymphocytes and neutrophils were unchanged in BAL fluid. 2. Increased numbers of eosinophils were detected in BAL 1 h after exposure to PAF but eosinophilia was not maximal until 48 h. One week after exposure to PAF, the percentage of eosinophils in BAL was within the normal range. 3. Depletion of circulating platelets or neutrophils by intravenous injection of specific antisera did not modify accumulation of eosinophils in the airway lumen following inhalation of PAF (10 micrograms ml-1). 4. PAF-induced pulmonary airway eosinophil accumulation was inhibited by treatment with SDZ 64-412, a selective PAF-antagonist, whether the compound was administered before, or 30 min after, inhalation of PAF. 5. Pulmonary airway eosinophil accumulation due to inhaled PAF (10 micrograms ml-1) was inhibited by prior treatment with aminophylline, cromoglycate, ketotifen, dexamethasone and AH 21-132. 6. Pulmonary airway eosinophil accumulation due to inhaled PAF (10 micrograms ml-1) was not inhibited by prior treatment with indomethacin, salbutamol or mepyramine. PMID:2328394

  16. Progress in Assessing Air Pollutant Risks from In Vitro Exposures: Matching Ozone Dose and Effect in Human Airway Cells

    PubMed Central

    Hatch, Gary E.; Duncan, Kelly E.; Diaz-Sanchez, David; Schmitt, Michael T.; Ghio, Andrew J.; Carraway, Martha Sue; McKee, John; Dailey, Lisa A.; Berntsen, Jon; Devlin, Robert B.

    2014-01-01

    In vitro exposures to air pollutants could, in theory, facilitate a rapid and detailed assessment of molecular mechanisms of toxicity. However, it is difficult to ensure that the dose of a gaseous pollutant to cells in tissue culture is similar to that of the same cells during in vivo exposure of a living person. The goal of the present study was to compare the dose and effect of O3 in airway cells of humans exposed in vivo to that of human cells exposed in vitro. Ten subjects breathed labeled O3 (18O3, 0.3 ppm, 2 h) while exercising intermittently. Bronchial brush biopsies and lung lavage fluids were collected 1 h post exposure for in vivo data whereas in vitro data were obtained from primary cultures of human bronchial epithelial cells exposed to 0.25–1.0 ppm 18O3 for 2 h. The O3 dose to the cells was defined as the level of 18O incorporation and the O3 effect as the fold increase in expression of inflammatory marker genes (IL-8 and COX-2). Dose and effect in cells removed from in vivo exposed subjects were lower than in cells exposed to the same 18O3 concentration in vitro suggesting upper airway O3 scrubbing in vivo. Cells collected by lavage as well as previous studies in monkeys show that cells deeper in the lung receive a higher O3 dose than cells in the bronchus. We conclude that the methods used herein show promise for replicating and comparing the in vivo dose and effect of O3 in an in vitro system. PMID:24928893

  17. Postentry Processing of Recombinant Adeno-Associated Virus Type 1 and Transduction of the Ferret Lung Are Altered by a Factor in Airway Secretions

    PubMed Central

    Yan, Ziying; Sun, Xingshen; Evans, Idil A.; Tyler, Scott R.; Song, Yi; Liu, Xiaoming; Sui, Hongshu

    2013-01-01

    Abstract We recently created a cystic fibrosis ferret model that acquires neonatal lung infection. To develop lung gene therapies for this model, we evaluated recombinant adeno-associated virus (rAAV)-mediated gene transfer to the neonatal ferret lung. Unlike in vitro ferret airway epithelial (FAE) cells, in vivo infection of the ferret lung with rAAV1 required proteasome inhibitors to achieve efficient airway transduction. We hypothesized that differences in transduction between these two systems were because of an in vivo secreted factor that alter the transduction biology of rAAV1. Indeed, treatment of rAAV1 with ferret airway secretory fluid (ASF) strongly inhibited rAAV1, but not rAAV2, transduction of primary FAE and HeLa cells. Properties of the ASF inhibitory factor included a strong affinity for the AAV1 capsid, heat-stability, negative charge, and sensitivity to endoproteinase Glu-C. ASF-treated rAAV1 dramatically inhibited apical transduction of FAE ALI cultures (512-fold), while only reducing viral entry by 55-fold, suggesting that postentry processing of virus was influenced by the inhibitor factor. Proteasome inhibitors rescued transduction in the presence of ASF (∼1600-fold) without effecting virus internalization, while proteasome inhibitors only enhanced transduction 45-fold in the absence of ASF. These findings demonstrate that a factor in lung secretions can influence intracellular processing of rAAV1 in a proteasome-dependent fashion. PMID:23948055

  18. Transcription Factor Runx3 Is Induced by Influenza A Virus and Double-Strand RNA and Mediates Airway Epithelial Cell Apoptosis

    PubMed Central

    Gan, Huachen; Hao, Qin; Idell, Steven; Tang, Hua

    2015-01-01

    Influenza A virus (IAV) targets airway epithelial cells and exploits the host cell machinery to replicate, causing respiratory illness in annual epidemics and pandemics of variable severity. The high rate of antigenic drift (viral mutation) and the putative antigenic shift (reassortant strains) have raised the need to find the host cell inducible factors modulating IAV replication and its pathogenesis to develop more effective antiviral treatment. In this study, we found for the first time that transcription factor Runx3, a developmental regulator and tumor suppressor, was induced by IAV H1N1 and H3N2, viral RNA, a synthetic analog of viral double-stranded RNA (dsRNA) polyinosinic-polycytidylic acid, and type-II interferon-γ (IFNγ) in human airway epithelial cells. Whereas Runx3 was essentially not induced by type-I IFNα and type-III IFNλ, we show that Runx3 induction by IAV infection and viral RNA is mediated through the innate immune receptor MDA5 and the IκB kinase-β−NF-κB pathway. Moreover, we provide substantial evidence indicating that Runx3 plays a crucial role in airway epithelial cell apoptosis induced by IAV infection and dsRNA through the activation of extrinsic and intrinsic apoptosis pathways. Thus, we have identified Runx3 as an inducible and important transcription factor modulating IAV-induced host epithelial cell apoptosis. PMID:26643317

  19. Calcineurin/Nuclear Factor of Activated T Cells–Coupled Vanilliod Transient Receptor Potential Channel 4 Ca2+ Sparklets Stimulate Airway Smooth Muscle Cell Proliferation

    PubMed Central

    Zhao, Limin; Sullivan, Michelle N.; Chase, Marlee; Gonzales, Albert L.

    2014-01-01

    Proliferation of airway smooth muscle cells (ASMCs) contributes to the remodeling and irreversible obstruction of airways during severe asthma, but the mechanisms underlying this disease process are poorly understood. Here we tested the hypothesis that Ca2+ influx through the vanilliod transient receptor potential channel (TRPV) 4 stimulates ASMC proliferation. We found that synthetic and endogenous TRPV4 agonists increase proliferation of primary ASMCs. Furthermore, we demonstrate that Ca2+ influx through individual TRPV4 channels produces Ca2+ microdomains in ASMCs, called “TRPV4 Ca2+ sparklets.” We also show that TRPV4 channels colocalize with the Ca2+/calmodulin–dependent protein phosphatase calcineurin in ASMCs. Activated calcineurin dephosphorylates nuclear factor of activated T cells (NFAT) transcription factors cytosolic (c) to allow nuclear translocation and activation of synthetic transcriptional pathways. We show that ASMC proliferation in response to TRPV4 activity is associated with calcineurin-dependent nuclear translocation of the NFATc3 isoform tagged with green florescent protein. Our findings suggest that Ca2+ microdomains created by TRPV4 Ca2+ sparklets activate calcineurin to stimulate nuclear translocation of NFAT and ASMC proliferation. These findings further suggest that inhibition of TRPV4 could diminish asthma-induced airway remodeling. PMID:24392954

  20. Airway clearance in neuromuscular weakness.

    PubMed

    Gauld, Leanne Maree

    2009-05-01

    Impaired airway clearance leads to recurrent chest infections and respiratory deterioration in neuromuscular weakness. It is frequently the cause of death. Cough is the major mechanism of airway clearance. Cough has several components, and assessment tools are available to measure the different components of cough. These include measuring peak cough flow, respiratory muscle strength, and inspiratory capacity. Each is useful in assessing the ability to generate an effective cough, and can be used to guide when techniques of assisting airway clearance may be effective for the individual and which are most effective. Techniques to assist airway clearance include augmenting inspiration by air stacking, augmenting expiration by assisting the cough, and augmenting both inspiration and expiration with the mechanical insufflator-exsufflator or by direct suctioning via a tracheostomy. Physiotherapists are invaluable in assisting airway clearance, and in teaching patients and their families how to use these techniques. Use of the mechanical insufflator-exsufflator has gained popularity in recent times, but several simpler, more economical methods are available to assist airway clearance that can be used effectively alone or in combination. This review examines the literature available on the assessment and management of impaired airway clearance in neuromuscular weakness. PMID:19379290

  1. USE OF WHOLE BODY PLETHSYMOGRAPHY TO ASSESS INFLUENCES OF RAT STRAIN AND AGE ON NONSPECIFIC AIRWAY RESPONSIVENESS

    EPA Science Inventory


    Increased airway responsiveness (AR) is a well-established characteristic of asthma that epidemiological evidence suggests may be linked to air pollutant exposure. Establishing the biologic basis between pollutant exposure and subsequent adverse public health outcome require...

  2. Mesenchymal stem cells and serelaxin synergistically abrogate established airway fibrosis in an experimental model of chronic allergic airways disease.

    PubMed

    Royce, Simon G; Shen, Matthew; Patel, Krupesh P; Huuskes, Brooke M; Ricardo, Sharon D; Samuel, Chrishan S

    2015-11-01

    This study determined if the anti-fibrotic drug, serelaxin (RLN), could augment human bone marrow-derived mesenchymal stem cell (MSC)-mediated reversal of airway remodeling and airway hyperresponsiveness (AHR) associated with chronic allergic airways disease (AAD/asthma). Female Balb/c mice subjected to the 9-week model of ovalbumin (OVA)-induced chronic AAD were either untreated or treated with MSCs alone, RLN alone or both combined from weeks 9-11. Changes in airway inflammation (AI), epithelial thickness, goblet cell metaplasia, transforming growth factor (TGF)-β1 expression, myofibroblast differentiation, subepithelial and total lung collagen deposition, matrix metalloproteinase (MMP) expression, and AHR were then assessed. MSCs alone modestly reversed OVA-induced subepithelial and total collagen deposition, and increased MMP-9 levels above that induced by OVA alone (all p<0.05 vs OVA group). RLN alone more broadly reversed OVA-induced epithelial thickening, TGF-β1 expression, myofibroblast differentiation, airway fibrosis and AHR (all p<0.05 vs OVA group). Combination treatment further reversed OVA-induced AI and airway/lung fibrosis compared to either treatment alone (all p<0.05 vs either treatment alone), and further increased MMP-9 levels. RLN appeared to enhance the therapeutic effects of MSCs in a chronic disease setting; most likely a consequence of the ability of RLN to limit TGF-β1-induced matrix synthesis complemented by the MMP-promoting effects of MSCs. PMID:26426509

  3. The B Lymphocyte Differentiation Factor (BAFF) Is Expressed in the Airways of Children with CF and in Lungs of Mice Infected with Pseudomonas aeruginosa

    PubMed Central

    Bricio-Moreno, Laura; Fothergill, Joanne L.; Southern, Kevin W.; Winstanley, Craig; Christmas, Stephen E.; Slupsky, Joseph R.; McNamara, Paul S.; Kadioglu, Aras; Flanagan, Brian F.

    2014-01-01

    Background Chronic lung infection with Pseudomonas aeruginosa remains a major cause of mortality and morbidity among individuals with CF. Expression of mediators promoting recruitment and differentiation of B cells, or supporting antibody production is poorly understood yet could be key to controlling infection. Methods BAFF was measured in BAL from children with CF, both with and without P. aeruginosa, and controls. Mice were intra-nasally infected with P. aeruginosa strain LESB65 for up to 7 days. Cellular infiltration and expression of B cell chemoattractants and B cell differentiation factor, BAFF were measured in lung tissue. Results BAFF expression was elevated in both P. aeruginosa negative and positive CF patients and in P. aeruginosa infected mice post infection. Expression of the B cell chemoattractants CXCL13, CCL19 and CCL21 increased progressively post infection. Conclusions In a mouse model, infection with P. aeruginosa was associated with elevated expression of BAFF and other B cell chemoattractants suggesting a role for airway B cell recruitment and differentiation in the local adaptive immune response to P. aeruginosa. The paediatric CF airway, irrespective of pseudomonal infection, was found to be associated with an elevated level of BAFF implying that BAFF expression is not specific to pseudomonas infection and may be a feature of the CF airway. Despite the observed presence of a potent B cell activator, chronic colonisation is common suggesting that this response is ineffective. PMID:24847941

  4. Capsaicin-induced mucus secretion in rat airways assessed in vivo and non-invasively by magnetic resonance imaging

    PubMed Central

    Karmouty-Quintana, H; Cannet, C; Sugar, R; Fozard, J R; Page, C P; Beckmann, N

    2007-01-01

    Background and purpose: An up-regulation of the sensory neural pathways in the lung has been implicated in asthma and chronic obstructive pulmonary disease (COPD) and is thought to contribute to mucus hypersecretion, an essential feature of both diseases. The aim of this study was to assess non-invasively the acute effects (up to 60 min) of sensory nerve stimulation by capsaicin in the lung, using magnetic resonance imaging (MRI). Experimental approach: Male Brown Norway rats were imaged prior to and 10, 30 and 60 min after intra-tracheal challenge with capsaicin (30 μgkg−1) or vehicle (0.5% ethanol solution). In subsequent studies, pre-treatment with the transient receptor potential vanilloid (TRPV)-1 antagonist, capsazepine; the dual neurokinin (NK) 1 and NK2 receptor antagonist, DNK333 and the mast cell stabilizer, di-sodium cromoglycate (DSCG) was used to modulate the effects of capsaicin. Key results: Diffuse fluid signals were detected by MRI in the lung as early as 10 min after capsaicin, remaining constant 30 and 60 min after treatment. Broncho-alveolar lavage (BAL) fluid analysis performed 60 min after capsaicin revealed increased mucin concentration. Capsazepine (3.5 mgkg−1), DNK333 (10 mgkg−1) but not DSCG (10 mgkg−1) administered prophylactically were able to block the effect of capsaicin in the airways. Conclusions and implications: These observations suggest that the fluid signals detected by MRI after capsaicin administration reflected predominantly the release of mucus following activation of sensory nerves. They point to the opportunity of non-invasively assessing with MRI the influence of neuronal mechanisms in animal models of asthma and COPD. PMID:17351665

  5. Irritant-induced airway disorders.

    PubMed

    Brooks, Stuart M; Bernstein, I Leonard

    2011-11-01

    Thousands of persons experience accidental high-level irritant exposures each year but most recover and few die. Irritants function differently than allergens because their actions proceed nonspecifically and by nonimmunologic mechanisms. For some individuals, the consequence of a single massive exposure to an irritant, gas, vapor or fume is persistent airway hyperresponsiveness and the clinical picture of asthma, referred to as reactive airways dysfunction syndrome (RADS). Repeated irritant exposures may lead to chronic cough and continual airway hyperresponsiveness. Cases of asthma attributed to repeated irritant-exposures may be the result of genetic and/or host factors. PMID:21978855

  6. NEUROTROPHIN MEDIATION OF ALLERGIC AIRWAYS RESPONSES TO INHALED DIESEL PARTICLES IN MICE

    EPA Science Inventory

    Neurotrophins, including nerve growth factor (NGF) partially mediate many features of allergic airways disease including airway hyper-responsiveness. Diesel exhaust particulates (DEP) associated with the combustion of diesel fuel exacerbate many of these allergic airways respons...

  7. Emergency airway puncture

    MedlinePlus

    Emergency airway puncture is the placement of a hollow needle through the throat into the airway. It ... Emergency airway puncture is done in an emergency situation, when someone is choking and all other efforts ...

  8. Eosinophilic phenotypes of airway disease.

    PubMed

    Pavord, Ian D

    2013-12-01

    Our understanding of the clinical implications of eosinophilic airway inflammation has increased significantly over the last 20 years, aided by the development of noninvasive means to assess it. This pattern of airway inflammation can occur in a diverse range of airway diseases. It is associated with a positive response to corticosteroids and a high risk of preventable exacerbations. Our new understanding of the role of eosinophilic airway inflammation has paved the way for the clinical development of a number of more specific inhibitors that may become new treatment options. Different definitions, ideas of disease, and adoption of biomarkers that are not well known are necessary to fully realize the potential of these treatments. PMID:24313765

  9. Blockage of upper airway

    MedlinePlus

    ... Airway obstruction - acute upper Images Throat anatomy Choking Respiratory system References Cukor J, Manno M. Pediatric respiratory emergencies: upper airway obstruction and infections. In: Marx ...

  10. Luteolin inhibited the gene expression, production and secretion of MUC5AC mucin via regulation of nuclear factor kappa B signaling pathway in human airway epithelial cells.

    PubMed

    Lee, Hyun Jae; Seo, Hyo-Seok; Ryu, Jiho; Yoon, Yong Pill; Park, Su Hyun; Lee, Choong Jae

    2015-04-01

    Luteolin, a flavonoidal compound derived from Lonicera japonica Thunb. and Chrysanthemum indicum L., has been reported to show anti-inflammatory, anti-oxidative and anti-carcinogenic effects. In this study, we investigated whether luteolin significantly affects the secretion, production and gene expression of airway mucin. Confluent NCI-H292 cells were pretreated with luteolin for 30 min and then stimulated with EGF (epidermal growth factor) or PMA (phorbol 12-myristate 13-acetate) for 24 h or the indicated periods. The MUC5AC mucin gene expression was measured by RT-PCR. Production and secretion of MUC5AC mucin protein were measured by ELISA. To elucidate the action mechanism of luteolin, effect of luteolin on PMA-induced NF-κB signaling pathway was investigated by western blot analysis. The results were as follows: (1) Luteolin inhibited the secretion of MUC5AC mucin protein induced by EGF or PMA; (2) Luteolin inhibited the production of MUC5AC mucin protein and the expression of MUC5AC mucin gene induced by EGF or PMA; (3) Luteolin inhibited PMA-induced phosphorylation and degradation of inhibitory kappa Bα (IκBα); (4) Luteolin inhibited PMA-induced phosphorylation and nuclear translocation of nuclear factor kappa B (NF-κB) p65. This result suggests that luteolin can regulate the secretion, production and gene expression of mucin by acting on airway epithelial cells via regulation of NF-kB signaling pathway. PMID:25285988

  11. Cervical computed tomography in patients with obstructive sleep apnea: influence of head elevation on the assessment of upper airway volume

    PubMed Central

    Souza, Fábio José Fabrício de Barros; Evangelista, Anne Rosso; Silva, Juliana Veiga; Périco, Grégory Vinícius; Madeira, Kristian

    2016-01-01

    Objective : Obstructive sleep apnea syndrome (OSAS) has a high prevalence and carries significant cardiovascular risks. It is important to study new therapeutic approaches to this disease. Positional therapy might be beneficial in reducing the apnea-hypopnea index (AHI). Imaging methods have been employed in order to facilitate the evaluation of the airways of OSAS patients and can be used in order to determine the effectiveness of certain treatments. This study was aimed at determining the influence that upper airway volume, as measured by cervical CT, has in patients diagnosed with OSAS. Methods : This was a quantitative, observational, cross-sectional study. We evaluated 10 patients who had been diagnosed with OSAS by polysomnography and on the basis of the clinical evaluation. All of the patients underwent conventional cervical CT in the supine position. Scans were obtained with the head of the patient in two positions (neutral and at a 44° upward inclination), and the upper airway volume was compared between the two. Results : The mean age, BMI, and neck circumference were 48.9 ± 14.4 years, 30.5 ± 3.5 kg/m2, and 40.3 ± 3.4 cm, respectively. The mean AHI was 13.7 ± 10.6 events/h (range, 6.0-41.6 events/h). The OSAS was classified as mild, moderate, and severe in 70%, 20%, and 10% of the patients, respectively. The mean upper airway volume was 7.9 cm3 greater when the head was at a 44° upward inclination than when it was in the neutral position, and that difference (17.5 ± 11.0%) was statistically significant (p = 0.002). Conclusions : Elevating the head appears to result in a significant increase in the caliber of the upper airways in OSAS patients. PMID:26982042

  12. Airway Surface Dehydration by Transforming Growth Factor β (TGF-β) in Cystic Fibrosis Is Due to Decreased Function of a Voltage-dependent Potassium Channel and Can Be Rescued by the Drug Pirfenidone.

    PubMed

    Manzanares, Dahis; Krick, Stefanie; Baumlin, Nathalie; Dennis, John S; Tyrrell, Jean; Tarran, Robert; Salathe, Matthias

    2015-10-16

    Transforming growth factor β1 (TGF-β1) is not only elevated in airways of cystic fibrosis (CF) patients, whose airways are characterized by abnormal ion transport and mucociliary clearance, but TGF-β1 is also associated with worse clinical outcomes. Effective mucociliary clearance depends on adequate airway hydration, governed by ion transport. Apically expressed, large-conductance, Ca(2+)- and voltage-dependent K(+) (BK) channels play an important role in this process. In this study, TGF-β1 decreased airway surface liquid volume, ciliary beat frequency, and BK activity in fully differentiated CF bronchial epithelial cells by reducing mRNA expression of the BK γ subunit leucine-rich repeat-containing protein 26 (LRRC26) and its function. Although LRRC26 knockdown itself reduced BK activity, LRRC26 overexpression partially reversed TGF-β1-induced BK dysfunction. TGF-β1-induced airway surface liquid volume hyper-absorption was reversed by the BK opener mallotoxin and the clinically useful TGF-β signaling inhibitor pirfenidone. The latter increased BK activity via rescue of LRRC26. Therefore, we propose that TGF-β1-induced mucociliary dysfunction in CF airways is associated with BK inactivation related to a LRRC26 decrease and is amenable to treatment with clinically useful TGF-β1 inhibitors. PMID:26338706

  13. Factors Influencing Adeno-Associated Virus-Mediated Gene Transfer to Human Cystic Fibrosis Airway Epithelial Cells: Comparison with Adenovirus Vectors

    PubMed Central

    Teramoto, S.; Bartlett, J. S.; McCarty, D.; Xiao, X.; Samulski, R. J.; Boucher, R. C.

    1998-01-01

    Adeno-associated virus (AAV) vectors appear promising for use in gene therapy in cystic fibrosis (CF) patients, yet many features of AAV-mediated gene transfer to airway epithelial cells are not well understood. We compared the transduction efficiencies of AAV vectors and adenovirus (Ad) vectors in immortalized cell lines from CF patients and in nasal epithelial primary cultures from normal humans and CF patients. Similar dose-dependent relationships between the vector multiplicities of infection and the efficiencies of lacZ gene transfer were observed. However, levels of transduction for both Ad and recombinant AAV (rAAV) were significantly lower in the airway epithelial cell than in the control cell lines HeLa and HEK 293. Transduction efficiencies differed among cultured epithelial cell types, with poorly differentiated cells transducing more efficiently than well-differentiated cells. A time-dependent increase in gene expression was observed after infection for both vectors. For Ad, but not for AAV, this increase was dependent on prolonged incubation of cells with the vector. Furthermore, for rAAV (but not for rAd), the delay in maximal transduction could be abrogated by wild-type Ad helper infection. Thus, although helper virus is not required for maximal transduction, it increases the kinetics by which this is achieved. Expression of Ad E4 open reading frame 6 or addition of either hydroxyurea or camptothecin resulted in increased AAV transduction, as previously demonstrated for nonairway cells (albeit to lower final levels), suggesting that second-strand synthesis may not be the sole cause of inefficient transduction. Finally, the efficiency of AAV-mediated ex vivo gene transfer to lung cells was similar to that previously described for Ad vectors in that transduction was limited to regions of epithelial injury and preferentially targeted basal-like cells. These studies address the primary factors influencing rAAV infection of human airway cells and should

  14. Factors influencing adeno-associated virus-mediated gene transfer to human cystic fibrosis airway epithelial cells: comparison with adenovirus vectors.

    PubMed

    Teramoto, S; Bartlett, J S; McCarty, D; Xiao, X; Samulski, R J; Boucher, R C

    1998-11-01

    Adeno-associated virus (AAV) vectors appear promising for use in gene therapy in cystic fibrosis (CF) patients, yet many features of AAV-mediated gene transfer to airway epithelial cells are not well understood. We compared the transduction efficiencies of AAV vectors and adenovirus (Ad) vectors in immortalized cell lines from CF patients and in nasal epithelial primary cultures from normal humans and CF patients. Similar dose-dependent relationships between the vector multiplicities of infection and the efficiencies of lacZ gene transfer were observed. However, levels of transduction for both Ad and recombinant AAV (rAAV) were significantly lower in the airway epithelial cell than in the control cell lines HeLa and HEK 293. Transduction efficiencies differed among cultured epithelial cell types, with poorly differentiated cells transducing more efficiently than well-differentiated cells. A time-dependent increase in gene expression was observed after infection for both vectors. For Ad, but not for AAV, this increase was dependent on prolonged incubation of cells with the vector. Furthermore, for rAAV (but not for rAd), the delay in maximal transduction could be abrogated by wild-type Ad helper infection. Thus, although helper virus is not required for maximal transduction, it increases the kinetics by which this is achieved. Expression of Ad E4 open reading frame 6 or addition of either hydroxyurea or camptothecin resulted in increased AAV transduction, as previously demonstrated for nonairway cells (albeit to lower final levels), suggesting that second-strand synthesis may not be the sole cause of inefficient transduction. Finally, the efficiency of AAV-mediated ex vivo gene transfer to lung cells was similar to that previously described for Ad vectors in that transduction was limited to regions of epithelial injury and preferentially targeted basal-like cells. These studies address the primary factors influencing rAAV infection of human airway cells and should

  15. Interaction between haemopoietic regulation and airway inflammation.

    PubMed

    O'Byrne, P M; Gauvreau, G M; Wood, L J

    1999-06-01

    Asthma is characterized by reversible airway narrowing, by airway hyperresponsiveness, and by airway inflammation. Inhaled allergens are the most important of the stimuli known to cause asthma. Methods for studying inhaled allergen in the laboratory have been well standardized and extensively used for the investigation of the pathophysiology and the pharmacological modulation of allergen-induced airway responses. Allergen inhalation by a sensitized subject results in an early asthmatic response, and, in the majority of subjects, a late asthmatic response and airway hyperresponsiveness. The late response and airway hyperresponsiveness are associated with increases in airway eosinophils and metachromatic cells. Allergen-induced airway inflammation in dogs (predominantly neutrophilic) is associated with increased granulocyte-macrophage progenitors in bone marrow, which is dependent on the effects of a circulating serum factor stimulating the bone marrow. The newly formed cells traffic to the airways. These increases in granulocyte-macrophage progenitors are blocked by inhaled corticosteroids. In human subjects, allergen-induced eosinophilic inflammation is associated with increases in Eo/B progenitors, mediated through up-regulation if the IL-5 receptor on progenitors and increases responsiveness to IL-5. Inhaled corticosteroids also attenuate all allergen-induced physiological responses and airway inflammation, an effect possibly mediated, in part, through inhibition of eosinophil and basophil maturation or release from the bone marrow. PMID:10421819

  16. Airway obstruction with cricoid pressure.

    PubMed

    Hartsilver, E L; Vanner, R G

    2000-03-01

    Cricoid pressure may cause airway obstruction. We investigated whether this is related to the force applied and to the technique of application. We recorded expired tidal volumes and inflation pressures during ventilation via a face-mask and oral airway in 52 female patients who were anaesthetised and about to undergo elective surgery. An inspired tidal volume of 900 ml was delivered using a ventilator. Ventilation was assessed under five different conditions: no cricoid pressure, backwards cricoid pressure applied with a force of 30 N, cricoid pressure applied in an upward and backward direction with a force of 30 N, backwards cricoid pressure with a force of 44 N and through a tracheal tube. An expired tidal volume of < 200 ml was taken to indicate airway obstruction. Airway obstruction did not occur without cricoid pressure, but did occur in one patient (2%) with cricoid pressure at 30 N, in 29 patients (56%) with 30 N applied in an upward and backward direction and in 18 (35%) patients with cricoid pressure at 44 N. Cricoid pressure applied with a force of 44 N can cause airway obstruction but if cricoid pressure is applied with a force of 30 N, airway obstruction occurs less frequently (p = 0.0001) unless the force is applied in an upward and backward direction. PMID:10671836

  17. Airway injury during high-level exercise.

    PubMed

    Kippelen, Pascale; Anderson, Sandra D

    2012-05-01

    Airway epithelial cells act as a physical barrier against environmental toxins and injury, and modulate inflammation and the immune response. As such, maintenance of their integrity is critical. Evidence is accumulating to suggest that exercise can cause injury to the airway epithelium. This seems the case particularly for competitive athletes performing high-level exercise, or when exercise takes place in extreme environmental conditions such as in cold dry air or in polluted air. Dehydration of the small airways and increased forces exerted on to the airway surface during severe hyperpnoea are thought to be key factors in determining the occurrence of injury of the airway epithelium. The injury-repair process of the airway epithelium may contribute to the development of the bronchial hyper-responsiveness that is documented in many elite athletes. PMID:22247295

  18. Small Airways Dysfunction in Asthma: Evaluation and Management to Improve Asthma Control

    PubMed Central

    2014-01-01

    The small airways have been neglected for many years, but interest in the topic has been rekindled with recent advances in measurement techniques to assess this region and also the ability to deliver therapeutics to the distal airways. Current levels of disease control in asthmatic patients remain poor and there are several contributory factors including; poor treatment compliance, heterogeneity of asthma phenotypes and associated comorbidities. However, the proposition that we may not be targeting all the inflammation that is present throughout the whole respiratory tree may also be an important factor. Indeed decades ago, pathologists and physiologists clearly identified the importance of small airways dysfunction in asthmatic patients. With improved inhaler technology to deliver drug to target the whole respiratory tree and more sensitive measures to assess the distal airways, we should certainly give greater consideration to treating the small airway region when seeing our asthmatic patients in clinic. The aim of this review is to address the relevance of small airways dysfunction in the daily clinical management of patients with asthma. In particular the role of small particle aerosols in the management of patients with asthma will be explored. PMID:25228994

  19. Potential of in vitro reconstituted 3D human airway epithelia (MucilAir™) to assess respiratory sensitizers.

    PubMed

    Huang, Song; Wiszniewski, Ludovic; Constant, Samuel; Roggen, Erwin

    2013-04-01

    Respiratory sensitizers are considered as substances of higher risk, at the same level as carcinogens, mutagens and toxic chemicals for reproduction. Presently, there is no validated assay for identifying the respiratory sensitizers. Based on a fully differentiated and functional in vitro cell model of the human airway epithelium, MucilAir™, we attempt to develop such assay. To this end, we invented a novel method, using Dextran as carrier, for applying the water insoluble chemicals to the apical surface of the airway epithelia. Using the Dextran carrier method, we successfully tested some reference chemical compounds known to cause respiratory sensitisation in human beings, including MDI, TMA and HCPt. Interestingly, these chemical sensitizers differentially up-regulated the releases of certain cytokines and chemokines involved in allergic responses. We believe that based on MucilAir™ an in vitro assay could be developed for identification and characterization of the respiratory sensitizers. PMID:23089132

  20. BET Bromodomains Regulate Transforming Growth Factor-β-induced Proliferation and Cytokine Release in Asthmatic Airway Smooth Muscle*

    PubMed Central

    Perry, Mark M.; Durham, Andrew L.; Austin, Philip J.; Adcock, Ian M.; Chung, Kian Fan

    2015-01-01

    Airway smooth muscle (ASM) mass is increased in asthma, and ASM cells from patients with asthma are hyperproliferative and release more IL-6 and CXCL8. The BET (bromo- and extra-terminal) family of proteins (Brd2, Brd3, and Brd4) govern the assembly of histone acetylation-dependent chromatin complexes. We have examined whether they modulate proliferation and cytokine expression in asthmatic ASM cells by studying the effect of BET bromodomain mimics JQ1/SGCBD01 and I-BET762. ASM cells from healthy individuals and nonsevere and severe asthmatics were pretreated with JQ1/SGCBD01 and I-BET762 prior to stimulation with FCS and TGF-β. Proliferation was measured by BrdU incorporation. IL-6 and CXCL8 release was measured by ELISA, and mRNA expression was measured by quantitative RT-PCR. ChIP using a specific anti-Brd4 antibody and PCR primers directed against the transcriptional start site of IL-6 and CXCL8 gene promoters was performed. Neither JQ1/SGCBD01 nor I-BET762 had any effect on ASM cell viability. JQ1/SGCBD01 and I-BET762 inhibited FCS+TGF-β-induced ASM cell proliferation and IL-6 and CXCL8 release in healthy individuals (≥ 30 nm) and in nonsevere and severe asthma patients (≥100 nm), with the latter requiring higher concentrations of these mimics. JQ1/SGCBD01 reduced Brd4 binding to IL8 and IL6 promoters induced by FCS+TGF-β. Mimics of BET bromodomains inhibit aberrant ASM cell proliferation and inflammation with lesser efficiency in those from asthmatic patients. They may be effective in reducing airway remodeling in asthma. PMID:25697361

  1. Automated lobe-based airway labeling.

    PubMed

    Gu, Suicheng; Wang, Zhimin; Siegfried, Jill M; Wilson, David; Bigbee, William L; Pu, Jiantao

    2012-01-01

    Regional quantitative analysis of airway morphological abnormalities is of great interest in lung disease investigation. Considering that pulmonary lobes are relatively independent functional unit, we develop and test a novel and efficient computerized scheme in this study to automatically and robustly classify the airways into different categories in terms of pulmonary lobe. Given an airway tree, which could be obtained using any available airway segmentation scheme, the developed approach consists of four basic steps: (1) airway skeletonization or centerline extraction, (2) individual airway branch identification, (3) initial rule-based airway classification/labeling, and (4) self-correction of labeling errors. In order to assess the performance of this approach, we applied it to a dataset consisting of 300 chest CT examinations in a batch manner and asked an image analyst to subjectively examine the labeled results. Our preliminary experiment showed that the labeling accuracy for the right upper lobe, the right middle lobe, the right lower lobe, the left upper lobe, and the left lower lobe is 100%, 99.3%, 99.3%, 100%, and 100%, respectively. Among these, only two cases are incorrectly labeled due to the failures in airway detection. It takes around 2 minutes to label an airway tree using this algorithm. PMID:23093951

  2. AIRTRAQ8 OPTICAL LARYNGOSCOPE FOR TRACHEAL INTUBATION IN A PATIENT WITH AN UNCOMMON GIANT LIPOMA ON THE POSTERIOR ASPECT OF NECK AND ADDITIONAL RISK FACTORS OF ANTICIPATED DIFFICULT AIRWAY: A CASE REPORT.

    PubMed

    Dimitriou, Vassilios; El Kouny, Amr; Al Harbi, Mohammed; Wambi, Freddie; Tawfeeq, Nasser; Tanweer, Aziz; Al Atassi, Abdulallem; Geldhof, Georges

    2015-10-01

    Patients with restricted neck movement present a difficult airway situation because of improper positioning and inadequate extension of the atlanto-occipital joint. The Airtraq optical laryngoscope is a new single use device that permits an indirect view of the glottis without the need to achieve a direct line of sight by conventional use of the 'sniffing position'. We present and discuss a case of uncommon giant lipoma (16 x 12 x 10 cm) in the posterior aspect of the neck in addition with other independent factors of anticipated difficult airway, intubated successfully in the semi-lateral position with the use of Airtraq. PMID:26860029

  3. Difficult Airway Response Team: A Novel Quality Improvement Program for Managing Hospital-Wide Airway Emergencies

    PubMed Central

    Mark, Lynette J.; Herzer, Kurt R.; Cover, Renee; Pandian, Vinciya; Bhatti, Nasir I.; Berkow, Lauren C.; Haut, Elliott R.; Hillel, Alexander T.; Miller, Christina R.; Feller-Kopman, David J.; Schiavi, Adam J.; Xie, Yanjun J.; Lim, Christine; Holzmueller, Christine; Ahmad, Mueen; Thomas, Pradeep; Flint, Paul W.; Mirski, Marek A.

    2015-01-01

    Background Difficult airway cases can quickly become emergencies, increasing the risk of life-threatening complications or death. Emergency airway management outside the operating room is particularly challenging. Methods We developed a quality improvement program—the Difficult Airway Response Team (DART)—to improve emergency airway management outside the operating room. DART was implemented by a team of anesthesiologists, otolaryngologists, trauma surgeons, emergency medicine physicians, and risk managers in 2005 at The Johns Hopkins Hospital in Baltimore, Maryland. The DART program had three core components: operations, safety, and education. The operations component focused on developing a multidisciplinary difficult airway response team, standardizing the emergency response process, and deploying difficult airway equipment carts throughout the hospital. The safety component focused on real-time monitoring of DART activations and learning from past DART events to continuously improve system-level performance. This objective entailed monitoring the paging system, reporting difficult airway events and DART activations to a web-based registry, and using in situ simulations to identify and mitigate defects in the emergency airway management process. The educational component included development of a multispecialty difficult airway curriculum encompassing case-based lectures, simulation, and team building/communication to ensure consistency of care. Educational materials were also developed for non-DART staff and patients to inform them about the needs of patients with difficult airways and ensure continuity of care with other providers after discharge. Results Between July 2008 and June 2013, DART managed 360 adult difficult airway events comprising 8% of all code activations. Predisposing patient factors included body mass index > 40, history of head and neck tumor, prior difficult intubation, cervical spine injury, airway edema, airway bleeding, and previous

  4. Assessing risk factors for periodontitis using regression

    NASA Astrophysics Data System (ADS)

    Lobo Pereira, J. A.; Ferreira, Maria Cristina; Oliveira, Teresa

    2013-10-01

    Multivariate statistical analysis is indispensable to assess the associations and interactions between different factors and the risk of periodontitis. Among others, regression analysis is a statistical technique widely used in healthcare to investigate and model the relationship between variables. In our work we study the impact of socio-demographic, medical and behavioral factors on periodontal health. Using regression, linear and logistic models, we can assess the relevance, as risk factors for periodontitis disease, of the following independent variables (IVs): Age, Gender, Diabetic Status, Education, Smoking status and Plaque Index. The multiple linear regression analysis model was built to evaluate the influence of IVs on mean Attachment Loss (AL). Thus, the regression coefficients along with respective p-values will be obtained as well as the respective p-values from the significance tests. The classification of a case (individual) adopted in the logistic model was the extent of the destruction of periodontal tissues defined by an Attachment Loss greater than or equal to 4 mm in 25% (AL≥4mm/≥25%) of sites surveyed. The association measures include the Odds Ratios together with the correspondent 95% confidence intervals.

  5. Recent insights into the relationship between airway inflammation and asthma.

    PubMed

    Siva, R; Berry, M; Pavord, I D

    2003-01-01

    There have been important recent advances in our understanding of the relationship between eosinophilic airway inflammation and airway dysfunction. Observational studies have shown that eosinophilic airway inflammation is not always present in asthma nor is it an exclusive feature of asthma. Its presence seems to be more closely linked to the presence of corticosteroid responsive airways disease and the occurrence of severe exacerbations than the presence of symptoms or the extent of airway dysfunction--indeed recent evidence suggests that in asthma these features may be more closely linked to the site of localisation of mast cells in the airway wall. One implication of this new understanding of the significance of eosinophilic airway inflammation is that it predicts that measuring airway inflammation might provide information that it is not readily available from a more traditional clinical assessment, and that patients might do better if this information is available. Recent studies support this view, showing a marked reduction in asthma exacerbation in patients with moderate to severe disease who are managed with reference to markers of airway inflammation as well as symptoms and simple tests of airway function. The development of new agents that have the potential to modulate specific aspects of airway inflammation, together with refinements in non-invasive techniques to assess the efficacy of these agents offers the prospect of further refining our understanding of the role of this aspect of the inflammatory response in asthma and other airway diseases. PMID:15148839

  6. Allergen-induced airway responses.

    PubMed

    Gauvreau, Gail M; El-Gammal, Amani I; O'Byrne, Paul M

    2015-09-01

    Environmental allergens are an important cause of asthma and can contribute to loss of asthma control and exacerbations. Allergen inhalation challenge has been a useful clinical model to examine the mechanisms of allergen-induced airway responses and inflammation. Allergen bronchoconstrictor responses are the early response, which reaches a maximum within 30 min and resolves by 1-3 h, and late responses, when bronchoconstriction recurs after 3-4 h and reaches a maximum over 6-12 h. Late responses are followed by an increase in airway hyperresponsiveness. These responses occur when IgE on mast cells is cross-linked by an allergen, causing degranulation and the release of histamine, neutral proteases and chemotactic factors, and the production of newly formed mediators, such as cysteinyl leukotrienes and prostaglandin D2. Allergen-induced airway inflammation consists of an increase in airway eosinophils, basophils and, less consistently, neutrophils. These responses are mediated by the trafficking and activation of myeloid dendritic cells into the airways, probably as a result of the release of epithelial cell-derived thymic stromal lymphopoietin, and the release of pro-inflammatory cytokines from type 2 helper T-cells. Allergen inhalation challenge has also been a widely used model to study potential new therapies for asthma and has an excellent negative predictive value for this purpose. PMID:26206871

  7. Upper airway test (image)

    MedlinePlus

    An upper airway biopsy is obtained by using a flexible scope called a bronchoscope. The scope is passed down through ... may be performed when an abnormality of the upper airway is suspected. It may also be performed as ...

  8. Anaesthetic management of acute airway obstruction

    PubMed Central

    Wong, Patrick; Wong, Jolin; Mok, May Un Sam

    2016-01-01

    The acutely obstructed airway is a medical emergency that can potentially result in serious morbidity and mortality. Apart from the latest advancements in anaesthetic techniques, equipment and drugs, publications relevant to our topic, including the United Kingdom’s 4th National Audit Project on major airway complications in 2011 and the updated American Society of Anesthesiologists’ difficult airway algorithm of 2013, have recently been published. The former contained many reports of adverse events associated with the management of acute airway obstruction. By analysing the data and concepts from these two publications, this review article provides an update on management techniques for the acutely obstructed airway. We discuss the principles and factors relevant to the decision-making process in formulating a logical management plan. PMID:26996162

  9. Anaesthetic management of acute airway obstruction.

    PubMed

    Wong, Patrick; Wong, Jolin; Mok, May Un Sam

    2016-03-01

    The acutely obstructed airway is a medical emergency that can potentially result in serious morbidity and mortality. Apart from the latest advancements in anaesthetic techniques, equipment and drugs, publications relevant to our topic, including the United Kingdom's 4th National Audit Project on major airway complications in 2011 and the updated American Society of Anesthesiologists' difficult airway algorithm of 2013, have recently been published. The former contained many reports of adverse events associated with the management of acute airway obstruction. By analysing the data and concepts from these two publications, this review article provides an update on management techniques for the acutely obstructed airway. We discuss the principles and factors relevant to the decision-making process in formulating a logical management plan. PMID:26996162

  10. Careers in Airway Science.

    ERIC Educational Resources Information Center

    Federal Aviation Administration (DOT), Washington, DC.

    The Federal Aviation Administration (FAA) has initiated the Airway Science curriculum as a method of preparing the next generation of aviation technicians and managers. This document: (1) discusses the FAA's role in the Airway Science program; (2) describes some of the career fields that FAA offers to Airway Science graduates (air traffic control…

  11. Importance of airway inflammation for hyperresponsiveness induced by ozone. [Dogs

    SciTech Connect

    Holtzman, M.J.; Fabbri, L.M.; O'Byrne, P.M.; Gold, B.D.; Aizawa, H.; Walters, E.H.; Alpert, S.E.; Nadel, J.A.

    1983-06-01

    We studied whether ozone-induced airway hyperresponsiveness correlates with the development of airway inflammation in dogs. To assess airway responsiveness, we determined increases in pulmonary resistance produced by delivering acetylcholine aerosol to the airways. To assess airway inflammation, we biopsied the airway mucosa and counted the number of neutrophils present in the epithelium. Airway responsiveness and inflammation were assessed in anesthetized dogs before ozone exposure and then 1 h and 1 wk after ozone (2.1 ppm, 2 h). Airway responsiveness increased markedly at 1 h after ozone and returned to control levels 1 wk later in each of 6 dogs, but it did not change after ozone in another 4 dogs. Furthermore, dogs that became hyperresponsive also developed a marked and reversible increase in the number of neutrophils in the epithelium, whereas dogs that did not become hyperresponsive had no change in the number of neutrophils. For the group of dogs, the level of airway responsiveness before and after ozone exposure correlated closely with the number of epithelial neutrophils. The results suggest that ozone-induced airway hyperresponsiveness may depend on the development of an acute inflammatory response in the airways.

  12. Airway and Extracellular Matrix Mechanics in COPD

    PubMed Central

    Bidan, Cécile M.; Veldsink, Annemiek C.; Meurs, Herman; Gosens, Reinoud

    2015-01-01

    Chronic obstructive pulmonary disease (COPD) is one of the most common lung diseases worldwide, and is characterized by airflow obstruction that is not fully reversible with treatment. Even though airflow obstruction is caused by airway smooth muscle contraction, the extent of airway narrowing depends on a range of other structural and functional determinants that impact on active and passive tissue mechanics. Cells and extracellular matrix in the airway and parenchymal compartments respond both passively and actively to the mechanical stimulation induced by smooth muscle contraction. In this review, we summarize the factors that regulate airway narrowing and provide insight into the relative contributions of different constituents of the extracellular matrix and their biomechanical impact on airway obstruction. We then review the changes in extracellular matrix composition in the airway and parenchymal compartments at different stages of COPD, and finally discuss how these changes impact airway narrowing and the development of airway hyperresponsiveness. Finally, we position these data in the context of therapeutic research focused on defective tissue repair. As a conclusion, we propose that future works should primarily target mild or early COPD, prior to the widespread structural changes in the alveolar compartment that are more characteristic of severe COPD. PMID:26696894

  13. Changes in airway permeability and responsiveness after exposure to ozone. [Sheep

    SciTech Connect

    Abraham, W.M.; Delehunt, J.C.; Yerger, L.; Marchette, B.; Oliver, W. Jr.

    1984-06-01

    The relationship between airway responsiveness and the permeability of histamine through the airways in conscious sheep after exposure to ozone (O/sub 3/ was examined). Airway responsiveness was assessed by measuring the change from baseline in mean pulmonary flow resistance following a controlled 2-min inhalation challenge with 1% histamine, containing 200 ..mu..Ci/ml of (/sup 3/H)histamine. The rate of appearance of the (/sup 3/H)histamine in the plasma during inhalation challenge was used to estimate airway permeability. To perturb the airways, conscious sheep were exposed to either 0.5 or 1.0 ppm O/sub 3/ for 2 hr via an endotracheal tube. Airway responsiveness and airway permeability were measured prior to and 1 day after exposure. In six sheep exposed to 0.5 ppm O/sub 3/, increased airway responsiveness and airway permeability were obseved 1 day after exposure. Four of seven sheep exposed to 1.0 ppm O/sub 3/ had enhanced airway responsiveness and airway permeability, while the remaining three sheep showed corresponding decreases in airway responsiveness and airway permeability. Since the O/sub 3/-induced directional changes in airway responsiveness paralleled the directional changes in airway permeability in both the positive and negative directions, it was concluded that changes in airway responsiveness to inhaled histamine following exposure to O/sub 3/ may be related to concomitant changes in airway permeability to this agent.

  14. IL-6 trans-signaling increases expression of airways disease genes in airway smooth muscle.

    PubMed

    Robinson, Mac B; Deshpande, Deepak A; Chou, Jeffery; Cui, Wei; Smith, Shelly; Langefeld, Carl; Hastie, Annette T; Bleecker, Eugene R; Hawkins, Gregory A

    2015-07-15

    Genetic data suggest that IL-6 trans-signaling may have a pathogenic role in the lung; however, the effects of IL-6 trans-signaling on lung effector cells have not been investigated. In this study, human airway smooth muscle (HASM) cells were treated with IL-6 (classical) or IL-6+sIL6R (trans-signaling) for 24 h and gene expression was measured by RNAseq. Intracellular signaling and transcription factor activation were assessed by Western blotting and luciferase assay, respectively. The functional effect of IL-6 trans-signaling was determined by proliferation assay. IL-6 trans-signaling had no effect on phosphoinositide-3 kinase and Erk MAP kinase pathways in HASM cells. Both classical and IL-6 trans-signaling in HASM involves activation of Stat3. However, the kinetics of Stat3 phosphorylation by IL-6 trans-signaling was different than classical IL-6 signaling. This was further reflected in the differential gene expression profile by IL-6 trans-signaling in HASM cells. Under IL-6 trans-signaling conditions 36 genes were upregulated, including PLA2G2A, IL13RA1, MUC1, and SOD2. Four genes, including CCL11, were downregulated at least twofold. The expression of 112 genes was divergent between IL-6 classical and trans-signaling, including the genes HILPDA, NNMT, DAB2, MUC1, WWC1, and VEGFA. Pathway analysis revealed that IL-6 trans-signaling induced expression of genes involved in regulation of airway remodeling, immune response, hypoxia, and glucose metabolism. Treatment of HASM cells with IL-6+sIL6R induced proliferation in a dose-dependent fashion, suggesting a role for IL-6 trans-signaling in asthma pathogenesis. These novel findings demonstrate differential effect of IL-6 trans-signaling on airway cells and identify IL-6 trans-signaling as a potential modifier of airway inflammation and remodeling. PMID:26001777

  15. Assessing the value of human factors initiatives.

    PubMed

    Kerr, Micky P; Knott, David S; Moss, Michael A; Clegg, Chris W; Horton, Robin P

    2008-05-01

    This paper examines the effectiveness of human factors initiatives and addresses some difficulties reported in calculating the value of such interventions. Company representatives and researchers applied a novel probabilistic assessment tool to estimate the financial impact of two macro-ergonomic projects. Key benefits of the company intranet project include reduced administrative and operational costs compared to a paper-based system; time savings for users asking for, providing and receiving information; and improved system usability and higher levels of usage. The communities of practice project demonstrates value through more efficient distribution and retrieval of information; reduced duplication by re-using technical knowledge to solve similar problems and improved sharing of good working practices, lessons and resources. The strengths of the tool include transparency, being quick and easy to learn and the collaborative workshop format, involving researches and key representatives from the organization. It makes a useful contribution to the challenge of assessing the financial value of ergonomic interventions, and, by exploiting its diagnostic and planning capabilities, could be extended to other domains. PMID:18096132

  16. A study of airway smooth muscle in asthmatic and non-asthmatic airways using PS-OCT (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Adams, David C.; Holz, Jasmin A.; Szabari, Margit V.; Hariri, Lida P.; Harris, R. Scott; Cho, Jocelyn L.; Hamilos, Daniel L.; Luster, Andrew D.; Medoff, Benjamin D.; Suter, Melissa J.

    2016-03-01

    Present understanding of the pathophysiological mechanisms of asthma has been severely limited by the lack of an imaging modality capable of assessing airway conditions of asthma patients in vivo. Of particular interest is the role that airway smooth muscle (ASM) plays in the development of asthma and asthma related symptoms. With standard Optical Coherence Tomography (OCT), imaging ASM is often not possible due to poor structural contrast between the muscle and surrounding tissues. A potential solution to this problem is to utilize additional optical contrast factors intrinsic to the tissue, such as birefringence. Due to its highly ordered structure, ASM is strongly birefringent. Previously, we demonstrated that Polarization Sensitive OCT(PS-OCT) has the potential to be used to visualize ASM as well as easily segment it from the surrounding (weakly) birefringent tissue by exploiting a property which allows it to discriminate the orientation of birefringent fibers. We have already validated our technology with a substantial set of histological comparisons made against data obtained ex vivo. In this work we present a comprehensive comparison of ASM distributions in asthmatic and non-asthmatic human volunteers. By isolating the ASM we parameterize its distribution in terms of both thickness and band width, calculated volumetrically over centimeters of airway. Using this data we perform analyses of the asthmatic and non-asthmatic airways using a broad number and variety and subjects.

  17. Assessment of the Microbial Constituents of the Home Environment of Individuals with Cystic Fibrosis (CF) and Their Association with Lower Airways Infections

    PubMed Central

    Heirali, Alya; McKeon, Suzanne; Purighalla, Swathi; Storey, Douglas G.; Rossi, Laura; Costilhes, Geoffrey; Drews, Steven J.; Rabin, Harvey R.; Surette, Michael G.; Parkins, Michael D.

    2016-01-01

    Introduction Cystic fibrosis (CF) airways are colonized by a polymicrobial community of organisms, termed the CF microbiota. We sought to define the microbial constituents of the home environment of individuals with CF and determine if it may serve as a latent reservoir for infection. Methods Six patients with newly identified CF pathogens were included. An investigator collected repeat sputum and multiple environmental samples from their homes. Bacteria were cultured under both aerobic and anaerobic conditions. Morphologically distinct colonies were selected, purified and identified to the genus and species level through 16S rRNA gene sequencing. When concordant organisms were identified in sputum and environment, pulsed-field gel electrophoresis (PFGE) was performed to determine relatedness. Culture-independent bacterial profiling of each sample was carried out by Illumina sequencing of the V3 region of the 16s RNA gene. Results New respiratory pathogens prompting investigation included: Mycobacterium abscessus(2), Stenotrophomonas maltophilia(3), Pseudomonas aeruginosa(3), Pseudomonas fluorescens(1), Nocardia spp.(1), and Achromobacter xylosoxidans(1). A median 25 organisms/patient were cultured from sputum. A median 125 organisms/home were cultured from environmental sites. Several organisms commonly found in the CF lung microbiome were identified within the home environments of these patients. Concordant species included members of the following genera: Brevibacterium(1), Microbacterium(1), Staphylococcus(3), Stenotrophomonas(2), Streptococcus(2), Sphingomonas(1), and Pseudomonas(4). PFGE confirmed related strains (one episode each of Sphinogomonas and P. aeruginosa) from the environment and airways were identified in two patients. Culture-independent assessment confirmed that many organisms were not identified using culture-dependent techniques. Conclusions Members of the CF microbiota can be found as constituents of the home environment in individuals with

  18. Sensory neuropeptides and airway function.

    PubMed

    Solway, J; Leff, A R

    1991-12-01

    Sensory nerves synthesize tachykinins and calcitonin-gene related peptide and package these neuropeptides together in synaptic vesicles. Stimulation of these C-fibers by a range of chemical and physical factors results in afferent neuronal conduction that elicits central parasympathetic reflexes and in antidromic conduction that results in local release of neuropeptides through the axon reflex. In the airways, sensory neuropeptides act on bronchial smooth muscle, the mucosal vasculature, and submucosal glands to promote airflow obstruction, hyperemia, microvascular hyperpermeability, and mucus hypersecretion. In addition, tachykinins potentiate cholinergic neurotransmission. Proinflammatory effects of these peptides also promote the recruitment, adherence, and activation of granulocytes that may further exacerbate neurogenic inflammation (i.e., neuropeptide-induced plasma extravasation and vasodilation). Enzymatic degradation limits the physiological effects of tachykinins but may be impaired by respiratory infection or other factors. Given their sensitivity to noxious compounds and physical stimuli and their potent effects on airway function, it is possible that neuropeptide-containing sensory nerves play an important role in mediating airway responses in human disease. Supporting this view are the striking phenomenological similarities between hyperpnea-induced bronchoconstriction (HIB) in guinea pigs and HIB in patients with exercise-induced asthma. Endogenous tachykinins released from airway sensory nerves mediate HIB in guinea pigs and also cause hyperpnea-induced bronchovascular hyperpermeability in these animals. On the basis of these observations, it is reasonable to speculate that sensory neuropeptides participate in the pathogenesis of hyperpnea-induced airflow obstruction in human asthmatic subjects as well. PMID:1663932

  19. The Physiologically Difficult Airway.

    PubMed

    Mosier, Jarrod M; Joshi, Raj; Hypes, Cameron; Pacheco, Garrett; Valenzuela, Terence; Sakles, John C

    2015-12-01

    Airway management in critically ill patients involves the identification and management of the potentially difficult airway in order to avoid untoward complications. This focus on difficult airway management has traditionally referred to identifying anatomic characteristics of the patient that make either visualizing the glottic opening or placement of the tracheal tube through the vocal cords difficult. This paper will describe the physiologically difficult airway, in which physiologic derangements of the patient increase the risk of cardiovascular collapse from airway management. The four physiologically difficult airways described include hypoxemia, hypotension, severe metabolic acidosis, and right ventricular failure. The emergency physician should account for these physiologic derangements with airway management in critically ill patients regardless of the predicted anatomic difficulty of the intubation. PMID:26759664

  20. The Physiologically Difficult Airway

    PubMed Central

    Mosier, Jarrod M.; Joshi, Raj; Hypes, Cameron; Pacheco, Garrett; Valenzuela, Terence; Sakles, John C.

    2015-01-01

    Airway management in critically ill patients involves the identification and management of the potentially difficult airway in order to avoid untoward complications. This focus on difficult airway management has traditionally referred to identifying anatomic characteristics of the patient that make either visualizing the glottic opening or placement of the tracheal tube through the vocal cords difficult. This paper will describe the physiologically difficult airway, in which physiologic derangements of the patient increase the risk of cardiovascular collapse from airway management. The four physiologically difficult airways described include hypoxemia, hypotension, severe metabolic acidosis, and right ventricular failure. The emergency physician should account for these physiologic derangements with airway management in critically ill patients regardless of the predicted anatomic difficulty of the intubation. PMID:26759664

  1. S100A8, S100A9 and S100A12 activate airway epithelial cells to produce MUC5AC via extracellular signal-regulated kinase and nuclear factor-κB pathways.

    PubMed

    Kang, Jin Hyun; Hwang, Sae Mi; Chung, Il Yup

    2015-01-01

    Airway mucus hyperproduction is a common feature of chronic airway diseases such as severe asthma, chronic obstructive pulmonary disease and cystic fibrosis, which are closely associated with neutrophilic airway inflammation. S100A8, S100A9 and S100A12 are highly abundant proteins released by neutrophils and have been identified as important biomarkers in many inflammatory diseases. Herein, we report a new role for S100A8, S100A9 and S100A12 for producing MUC5AC, a major mucin protein in the respiratory tract. All three S100 proteins induced MUC5AC mRNA and the protein in normal human bronchial epithelial cells as well as NCI-H292 lung carcinoma cells in a dose-dependent manner. A Toll-like receptor 4 (TLR4) inhibitor almost completely abolished MUC5AC expression by all three S100 proteins, while neutralization of the receptor for advanced glycation end-products (RAGE) inhibited only S100A12-mediated production of MUC5AC. The S100 protein-mediated production of MUC5AC was inhibited by the pharmacological agents that block prominent signalling molecules for MUC5AC expression, such as mitogen-activated protein kinases, nuclear factor-κB (NF-κB) and epidermal growth factor receptor. S100A8, S100A9 and S100A12 equally elicited both phosphorylation of extracellular signal-regulated kinase (ERK) and nuclear translocation of NF-κB/degradation of cytosolic IκB with similar kinetics through TLR4. In contrast, S100A12 preferentially activated the ERK pathway rather than the NF-κB pathway through RAGE. Collectively, these data reveal the capacity of these three S100 proteins to induce MUC5AC production in airway epithelial cells, suggesting that they all serve as key mediators linking neutrophil-dominant airway inflammation to mucin hyperproduction. PMID:24975020

  2. Intrathoracic airway measurement: ex-vivo validation

    NASA Astrophysics Data System (ADS)

    Reinhardt, Joseph M.; Raab, Stephen A.; D'Souza, Neil D.; Hoffman, Eric A.

    1997-05-01

    High-resolution x-ray CT (HRCT) provides detailed images of the lungs and bronchial tree. HRCT-based imaging and quantitation of peripheral bronchial airway geometry provides a valuable tool for assessing regional airway physiology. Such measurements have been sued to address physiological questions related to the mechanics of airway collapse in sleep apnea, the measurement of airway response to broncho-constriction agents, and to evaluate and track the progression of disease affecting the airways, such as asthma and cystic fibrosis. Significant attention has been paid to the measurements of extra- and intra-thoracic airways in 2D sections from volumetric x-ray CT. A variety of manual and semi-automatic techniques have been proposed for airway geometry measurement, including the use of standardized display window and level settings for caliper measurements, methods based on manual or semi-automatic border tracing, and more objective, quantitative approaches such as the use of the 'half-max' criteria. A recently proposed measurements technique uses a model-based deconvolution to estimate the location of the inner and outer airway walls. Validation using a plexiglass phantom indicates that the model-based method is more accurate than the half-max approach for thin-walled structures. In vivo validation of these airway measurement techniques is difficult because of the problems in identifying a reliable measurement 'gold standard.' In this paper we report on ex vivo validation of the half-max and model-based methods using an excised pig lung. The lung is sliced into thin sections of tissue and scanned using an electron beam CT scanner. Airways of interest are measured from the CT images, and also measured with using a microscope and micrometer to obtain a measurement gold standard. The result show no significant difference between the model-based measurements and the gold standard; while the half-max estimates exhibited a measurement bias and were significantly

  3. Non-invasive airway health assessment: Synchrotron imaging reveals effects of rehydrating treatments on mucociliary transit in-vivo

    NASA Astrophysics Data System (ADS)

    Donnelley, Martin; Morgan, Kaye S.; Siu, Karen K. W.; Farrow, Nigel R.; Stahr, Charlene S.; Boucher, Richard C.; Fouras, Andreas; Parsons, David W.

    2014-01-01

    To determine the efficacy of potential cystic fibrosis (CF) therapies we have developed a novel mucociliary transit (MCT) measurement that uses synchrotron phase contrast X-ray imaging (PCXI) to non-invasively measure the transit rate of individual micron-sized particles deposited into the airways of live mice. The aim of this study was to image changes in MCT produced by a rehydrating treatment based on hypertonic saline (HS), a current CF clinical treatment. Live mice received HS containing a long acting epithelial sodium channel blocker (P308); isotonic saline; or no treatment, using a nebuliser integrated within a small-animal ventilator circuit. Marker particle motion was tracked for 20 minutes using PCXI. There were statistically significant increases in MCT in the isotonic and HS-P308 groups. The ability to quantify in vivo changes in MCT may have utility in pre-clinical research studies designed to bring new genetic and pharmaceutical treatments for respiratory diseases into clinical trials.

  4. Prevention of non-specific airway hyperreactivity after allergen challenge in guinea-pigs by the PAF receptor antagonist SDZ 64-412.

    PubMed Central

    Havill, A. M.; Van Valen, R. G.; Handley, D. A.

    1990-01-01

    1. Allergen challenge by aerosol in sensitized guinea-pigs elicited non-specific airway hyperreactivity assessed by reactivity to i.v. histamine or acetylcholine. Airway hyperreactivity to histamine persisted for at least 48 h and was accompanied by pulmonary eosinophilia as determined by bronchoalveolar lavage cell analysis. 2. Airway hyperreactivity was independent of vagal reflex mechanisms since it was not abrogated by bilateral vagotomy. 3. The novel platelet-activating factor (PAF) receptor antagonist SDZ 64-412 inhibited the development of airway hyperreactivity, as measured 24 h after aerosol allergen challenge, when given as a single treatment orally 2 h before allergen challenge. The PAF receptor antagonist WEB 2086 as well as methylprednisolone and ketotifen also showed efficacy in preventing development of airway hyperreactivity. 4. Neither the two PAF antagonists nor ketotifen had any effect on bronchoalveolar lavage (BAL) eosinophil numbers. Methylprednisolone was the only substance which readily prevented eosinophil recruitment in addition to airway hyperreactivity. 5. We conclude that allergen-induced airway hyperreactivity in guinea-pigs is inhibited by prophylactic anti-asthma drugs and specific PAF receptor antagonists, thus demonstrating a pivotal role of PAF in this response. There was a lack of correlation between airway hyperreactivity and the presence of BAL eosinophils. PMID:2328403

  5. Multum non multa: airway distensibility by forced oscillations.

    PubMed

    Mermigkis, Charalampos; Schiza, Sophia E; Panagou, Panagiotis

    2016-01-01

    Airway distensibility although appears to be unaffected by airway smooth muscle tone probably related to airway remodelling, after bronchodilator treatment is significantly increased in subjects with asthma. We assessed airway distensibity and its first moment derivative in two patients with mild intermittent asthma and normal spirometry. The increase in airway distensibility after bronchodilation measured at the tidal volume range during quiet breathing by forced oscillations was not accompanied by a change in its first moment, while the latter showed a significant increase in a second patient after anti-inflammatory treatment. It appears that airway distensibility is sensitive to reduction of bronchial smooth muscle tone after bronchodilation, but in addition its first moment might provide information on a change of both bronchial smooth muscle tone and small airways inflammation. PMID:27374218

  6. Human airway measurement from CT images

    NASA Astrophysics Data System (ADS)

    Lee, Jaesung; Reeves, Anthony P.; Fotin, Sergei; Apanasovich, Tatiyana; Yankelevitz, David

    2008-03-01

    A wide range of pulmonary diseases, including common ones such as COPD, affect the airways. If the dimensions of airway can be measured with high confidence, the clinicians will be able to better diagnose diseases as well as monitor progression and response to treatment. In this paper, we introduce a method to assess the airway dimensions from CT scans, including the airway segments that are not oriented axially. First, the airway lumen is segmented and skeletonized, and subsequently each airway segment is identified. We then represent each airway segment using a segment-centric generalized cylinder model and assess airway lumen diameter (LD) and wall thickness (WT) for each segment by determining inner and outer wall boundaries. The method was evaluated on 14 healthy patients from a Weill Cornell database who had two scans within a 2 month interval. The corresponding airway segments were located in two scans and measured using the automated method. The total number of segments identified in both scans was 131. When 131 segments were considered altogether, the average absolute change over two scans was 0.31 mm for LD and 0.12 mm for WT, with 95% limits of agreement of [-0.85, 0.83] for LD and [-0.32, 0.26] for WT. The results were also analyzed on per-patient basis, and the average absolute change was 0.19 mm for LD and 0.05 mm for WT. 95% limits of agreement for per-patient changes were [-0.57, 0.47] for LD and [-0.16, 0.10] for WT.

  7. Bronchoconstriction and airway biology: potential impact and therapeutic opportunities.

    PubMed

    Gosens, Reinoud; Grainge, Chris

    2015-03-01

    Recent work has demonstrated that mechanical forces occurring in the airway as a consequence of bronchoconstriction are sufficient to not only induce symptoms but also influence airway biology. Animal and human in vitro and in vivo work demonstrates that the airways are structurally and functionally altered by mechanical stress induced by bronchoconstriction. Compression of the airway epithelium and mechanosensing by the airway smooth muscle trigger the activation and release of growth factors, causing cell proliferation, extracellular matrix protein accumulation, and goblet cell differentiation. These effects of bronchoconstriction are of major importance to asthma pathophysiology and appear sufficient to induce remodeling independent of the inflammatory response. We review these findings in detail and discuss previous studies in light of this new evidence regarding the influence of mechanical forces in the airways. Furthermore, we highlight potential impacts of therapies influencing mechanical forces on airway structure and function in asthma. PMID:25732446

  8. Activation of transcription factor IL-6 (NF-IL-6) and nuclear factor-kappaB (NF-kappaB) by lipid ozonation products is crucial to interleukin-8 gene expression in human airway epithelial cells.

    PubMed

    Kafoury, Ramzi M; Hernandez, Jazmir M; Lasky, Joseph A; Toscano, William A; Friedman, Mitchell

    2007-04-01

    Ozone (O(3)) is a major component of smog and an inhaled toxicant to the lung. O(3) rapidly reacts with the airway epithelial cell membrane phospholipids to generate lipid ozonation products (LOP). 1-Hydroxy-1-hydroperoxynonane (HHP-C9) is an important LOP, produced from the ozonation of 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphatidylcholine. This LOP, at a biologically relevant concentration (100 microM), increases the activity of phospholipase C, nuclear factors-kappaB (NF-kappaB), and interleukin-6 (NF-IL-6) and the expression of the inflammatory gene, interleukin-8 (IL-8) in a cultured human bronchial epithelial cell line (BEAS-2B). The signaling pathways of ozone and its biologically-active products are as yet undefined. In the present study, we report that the HHP LOP, HHP-C9 (100 microM x 4 h), activated the expression of IL-8 (218 +/- 26% increase over control, n = 4, P < 0.01) through an apparent interaction between the two transcription factors, NF-kappaB and NF-IL-6. Transfection studies using luciferase reporter assays demonstrated that HHP-C9 induced a significant increase in NF-kappaB-DNA binding activity (37 +/- 7% increase over control, n = 6, P < 0.05). Inhibition of NF-kappaB showed a statistically significant but modest decrease in IL-8 release, which suggested a role for another transcription factor, NF-IL-6. Exposure of BEAS-2B cells to HHP-C9 induced a significant increase in the DNA binding activity of NF-IL-6 (45 +/- 11% increase over control, n = 6, P < 0.05). The results of the present study indicate that NF-IL-6 interacts with NF-kappaB in regulating the expression of IL-8 in cultured human airway epithelial cells exposed to LOP, the biological products of ozone in the lung. PMID:17366569

  9. Therapeutic bronchoscopic interventions for malignant airway obstruction

    PubMed Central

    Dalar, Levent; Özdemir, Cengiz; Abul, Yasin; Karasulu, Levent; Sökücü, Sinem Nedime; Akbaş, Ayşegül; Altın, Sedat

    2016-01-01

    Abstract There is no definitive consensus about the factors affecting the choice of interventional bronchoscopy in the management of malignant airway obstruction. The present study defines the choice of the interventional bronchoscopic modality and analyzes the factors influencing survival in patients with malignant central airway obstruction. Totally, over 7 years, 802 interventional rigid bronchoscopic procedures were applied in 547 patients having malignant airway obstruction. There was a significant association between the type of stent and the site of the lesion in the present study. Patients with tracheal involvement and/or involvement of the main bronchi had the worst prognosis. The sites of the lesion and endobronchial treatment modality were independent predictors of survival in the present study. The selection of different types of airway stents can be considered on the base of site of the lesion. Survival can be estimated based on the site of the lesion and endobronchial brochoscopic modality used. PMID:27281104

  10. Exposure to welding fumes and lower airway infection with Streptococcus pneumoniae

    PubMed Central

    Suri, Reetika; Periselneris, Jimstan; Lanone, Sophie; Zeidler-Erdely, Patti C.; Melton, Geoffrey; Palmer, Keith T.; Andujar, Pascal; Antonini, James M.; Cohignac, Vanessa; Erdely, Aaron; Jose, Ricardo J.; Mudway, Ian; Brown, Jeremy; Grigg, Jonathan

    2015-01-01

    Background Welders are at increased risk of pneumococcal pneumonia. The mechanism for this association is not known. The capacity of pneumococci to adhere to and infect lower airway cells is mediated by host-expressed platelet-activating factor receptor (PAFR). Objective We sought to assess the effect of mild steel welding fumes (MS-WF) on PAFR-dependent pneumococcal adhesion and infection to human airway cells in vitro and on pneumococcal airway infection in a mouse model. Methods The oxidative potential of MS-WF was assessed by their capacity to reduce antioxidants in vitro. Pneumococcal adhesion and infection of A549, BEAS-2B, and primary human bronchial airway cells were assessed by means of quantitative bacterial culture and expressed as colony-forming units (CFU). After intranasal instillation of MS-WF, mice were infected with Streptococcus pneumoniae, and bronchoalveolar lavage fluid (BALF) and lung CFU values were determined. PAFR protein levels were assessed by using immunofluorescence and immunohistochemistry, and PAFR mRNA expression was assessed by using quantitative PCR. PAFR was blocked by CV-3988, and oxidative stress was attenuated by N-acetylcysteine. Results: MS-WF exhibited high oxidative potential. In A549 and BEAS-2B cells MS-WF increased pneumococcal adhesion and infection and PAFR protein expression. Both CV-3988 and N-acetylcysteine reduced MS-WF–stimulated pneumococcal adhesion and infection of airway cells. MS-WF increased mouse lung PAFR mRNA expression and increased BALF and lung pneumococcal CFU values. In MS-WF–exposed mice CV-3988 reduced BALF CFU values. Conclusions Hypersusceptibility of welders to pneumococcal pneumonia is in part mediated by the capacity of welding fumes to increase PAFR-dependent pneumococcal adhesion and infection of lower airway cells. PMID:26277596

  11. BLOCKADE OF TRKA OR P75 NEUROTROPHIN RECEPTORS ATTENUATES DIESEL PARTICULATE-INDUCED ENHANCEMENT OF ALLERGIC AIRWAYS RESPONSES IN BALB/C MICE

    EPA Science Inventory

    Neurotrophins, including nerve growth factor (NGF) partially mediate many features of allergic airways disease including airway resistance. Exposure to diesel exhaust particles (DEP) associated with the combustion of diesel fuel exacerbates allergic airways responses. We tested t...

  12. Lung Transplantation: The State of the Airways.

    PubMed

    Husain, Aliya N; Garrity, Edward R

    2016-03-01

    Context .- Lung transplantation has become a viable option for definitive treatment of several end-stage lung diseases for which there are no other options available. However, long-term survival continues to be limited by chronic lung allograft dysfunction, which primarily affects the airways. Objective . -To highlight the complications occurring mainly in the airways of the lung transplant recipient from the early to late posttransplant periods. Data Sources .- Review literature focusing on the airways in patients with lung transplants and clinical experience of the authors. Conclusions .- Postsurgical complications and infections of the airways have decreased because of better techniques and management. Acute cellular rejection of the airways can be distinguished from infection pathologically and on cultures. Separating small from large airways need not be an issue because both are risk factors for bronchiolitis obliterans. Grading of airway rejection needs to be standardized. Chronic lung allograft dysfunction consists of both bronchiolitis obliterans and restrictive allograft syndrome, neither of which can be treated very effectively at present. PMID:26927718

  13. Engineering Airway Epithelium

    PubMed Central

    Soleas, John P.; Paz, Ana; Marcus, Paula; McGuigan, Alison; Waddell, Thomas K.

    2012-01-01

    Airway epithelium is constantly presented with injurious signals, yet under healthy circumstances, the epithelium maintains its innate immune barrier and mucociliary elevator function. This suggests that airway epithelium has regenerative potential (I. R. Telford and C. F. Bridgman, 1990). In practice, however, airway regeneration is problematic because of slow turnover and dedifferentiation of epithelium thereby hindering regeneration and increasing time necessary for full maturation and function. Based on the anatomy and biology of the airway epithelium, a variety of tissue engineering tools available could be utilized to overcome the barriers currently seen in airway epithelial generation. This paper describes the structure, function, and repair mechanisms in native epithelium and highlights specific and manipulatable tissue engineering signals that could be of great use in the creation of artificial airway epithelium. PMID:22523471

  14. B Cell-Activating Transcription Factor Plays a Critical Role in the Pathogenesis of Anti-Major Histocompatibility Complex-Induced Obliterative Airway Disease.

    PubMed

    Xu, Z; Ramachandran, S; Gunasekaran, M; Nayak, D; Benshoff, N; Hachem, R; Gelman, A; Mohanakumar, T

    2016-04-01

    Antibodies (Abs) against major histocompatibility complex (MHC) results in T helper-17 (Th17)-mediated immunity against lung self-antigens (SAgs), K-α1 tubulin and collagen V and obliterative airway disease (OAD). Because B cell-activating transcription factor (BATF) controls Th17 and autoimmunity, we proposed that BATF may play a critical role in OAD. Anti-H2K(b) was administered intrabronchially into Batf (-/-) and C57BL/6 mice. Histopathology of the lungs on days 30 and 45 after Ab administration to Batf (-/-) mice resulted in decreased cellular infiltration, epithelial metaplasia, fibrosis, and obstruction. There was lack of Abs to SAgs, reduction of Sag-specific interleukin (IL)-17 T cells, IL-6, IL-23, IL-17, IL-1β, fibroblast growth factor-6, and CXCL12 and decreased Janus kinase 2, signal transducer and activator of transcription 3 (STAT3), and retinoid-related orphan receptor γT. Further, micro-RNA (miR)-301a, a regulator of Th17, was reduced in Batf (-/-) mice in contrast to upregulation of miR-301a and downregulation of protein inhibitor of activated STAT3 (PIAS3) in anti-MHC-induced OAD animals. We also demonstrate an increase in miR-301a in the bronchoalveolar lavage cells from lung transplant recipients with Abs to human leukocyte antigen. This was accompanied by reduction in PIAS3 mRNA. Therefore, we conclude that BATF plays a critical role in the immune responses to SAgs and pathogenesis of anti-MHC-induced rejection. Targeting BATF should be considered for preventing chronic rejection after human lung transplantation. PMID:26844425

  15. Conquering the difficult airway.

    PubMed

    Gandy, William E

    2008-01-01

    Every medic should practice regularly for the inevitable difficult airway case. Practice should include review of the causes of difficult airways, as well as skill practice. Having a preassembled airway kit can make your response to an unexpected difficult situation easier. Of all the devices mentioned, the bougie is the airway practitioner's best friend. Using the BURP technique, if not contraindicated, together with the bougie will enable you to intubate many difficult patients with confidence. Remember, "If your patient cannot breathe, nothing else matters. PMID:18251307

  16. Automated airway evaluation system for multi-slice computed tomography using airway lumen diameter, airway wall thickness and broncho-arterial ratio

    NASA Astrophysics Data System (ADS)

    Odry, Benjamin L.; Kiraly, Atilla P.; Novak, Carol L.; Naidich, David P.; Lerallut, Jean-Francois

    2006-03-01

    Pulmonary diseases such as bronchiectasis, asthma, and emphysema are characterized by abnormalities in airway dimensions. Multi-slice computed tomography (MSCT) has become one of the primary means to depict these abnormalities, as the availability of high-resolution near-isotropic data makes it possible to evaluate airways at oblique angles to the scanner plane. However, currently, clinical evaluation of airways is typically limited to subjective visual inspection only: systematic evaluation of the airways to take advantage of high-resolution data has not proved practical without automation. We present an automated method to quantitatively evaluate airway lumen diameter, wall thickness and broncho-arterial ratios. In addition, our method provides 3D visualization of these values, graphically illustrating the location and extent of disease. Our algorithm begins by automatic airway segmentation to extract paths to the distal airways, and to create a map of airway diameters. Normally, airway diameters decrease as paths progress distally; failure to taper indicates abnormal dilatation. Our approach monitors airway lumen diameters along each airway path in order to detect abnormal profiles, allowing even subtle degrees of pathologic dilatation to be identified. Our method also systematically computes the broncho-arterial ratio at every terminal branch of the tree model, as a ratio above 1 indicates potentially abnormal bronchial dilatation. Finally, the airway wall thickness is computed at corresponding locations. These measurements are used to highlight abnormal branches for closer inspection, and can be summed to compute a quantitative global score for the entire airway tree, allowing reproducible longitudinal assessment of disease severity. Preliminary tests on patients diagnosed with bronchiectasis demonstrated rapid identification of lack of tapering, which also was confirmed by corresponding demonstration of elevated broncho-arterial ratios.

  17. Airway smooth muscle in airway reactivity and remodeling: what have we learned?

    PubMed Central

    2013-01-01

    It is now established that airway smooth muscle (ASM) has roles in determining airway structure and function, well beyond that as the major contractile element. Indeed, changes in ASM function are central to the manifestation of allergic, inflammatory, and fibrotic airway diseases in both children and adults, as well as to airway responses to local and environmental exposures. Emerging evidence points to novel signaling mechanisms within ASM cells of different species that serve to control diverse features, including 1) [Ca2+]i contractility and relaxation, 2) cell proliferation and apoptosis, 3) production and modulation of extracellular components, and 4) release of pro- vs. anti-inflammatory mediators and factors that regulate immunity as well as the function of other airway cell types, such as epithelium, fibroblasts, and nerves. These diverse effects of ASM “activity” result in modulation of bronchoconstriction vs. bronchodilation relevant to airway hyperresponsiveness, airway thickening, and fibrosis that influence compliance. This perspective highlights recent discoveries that reveal the central role of ASM in this regard and helps set the stage for future research toward understanding the pathways regulating ASM and, in turn, the influence of ASM on airway structure and function. Such exploration is key to development of novel therapeutic strategies that influence the pathophysiology of diseases such as asthma, chronic obstructive pulmonary disease, and pulmonary fibrosis. PMID:24142517

  18. Quantitative computed tomography imaging of airway remodeling in severe asthma.

    PubMed

    Grenier, Philippe A; Fetita, Catalin I; Brillet, Pierre-Yves

    2016-02-01

    Asthma is a heterogeneous condition and approximately 5-10% of asthmatic subjects have severe disease associated with structure changes of the airways (airway remodeling) that may develop over time or shortly after onset of disease. Quantitative computed tomography (QCT) imaging of the tracheobronchial tree and lung parenchyma has improved during the last 10 years, and has enabled investigators to study the large airway architecture in detail and assess indirectly the small airway structure. In severe asthmatics, morphologic changes in large airways, quantitatively assessed using 2D-3D airway registration and recent algorithms, are characterized by airway wall thickening, luminal narrowing and bronchial stenoses. Extent of expiratory gas trapping, quantitatively assessed using lung densitometry, may be used to assess indirectly small airway remodeling. Investigators have used these quantitative imaging techniques in order to attempt severity grading of asthma, and to identify clusters of asthmatic patients that differ in morphologic and functional characteristics. Although standardization of image analysis procedures needs to be improved, the identification of remodeling pattern in various phenotypes of severe asthma and the ability to relate airway structures to important clinical outcomes should help target treatment more effectively. PMID:26981458

  19. Airway Inflammation and Hypersensitivity Induced by Chronic Smoking

    PubMed Central

    Kou, Yu Ru; Kwong, Kevin; Lee, Lu-Yuan

    2011-01-01

    Airway hypersensitivity, characterized by enhanced excitability of airway sensory nerves, is a prominent pathophysiological feature in patients with airway inflammatory diseases. Although the underlying pathogenic mechanism is not fully understood, chronic airway inflammation is believed to be primarily responsible. Cigarette smoking is known to cause chronic airway inflammation, accompanied by airway hyperresponsiveness. Experimental evidence indicates that enhanced excitability of vagal bronchopulmonary sensory nerves and increased tachykinin synthesis in these nerves resulting from chronic inflammation are important contributing factors to the airway hyperresponsiveness. Multiple inflammatory mediators released from various types of structural and inflammatory cells are involved in the smoking-induced airway inflammation, which is mainly regulated by redox-sensitive signaling pathways and transcription factors. Furthermore, recent studies have reported potent sensitizing and stimulatory effects of these inflammatory mediators such as prostanoids and reactive oxygen species on these sensory nerves. In summary, these studies using cigarette smoking as an experimental approach have identified certain potentially important cell signaling pathways and underlying mechanisms of the airway hypersensitivity induced by chronic airway inflammation. PMID:21397052

  20. Activity of abundant antimicrobials of the human airway.

    PubMed

    Travis, S M; Conway, B A; Zabner, J; Smith, J J; Anderson, N N; Singh, P K; Greenberg, E P; Welsh, M J

    1999-05-01

    Human airways produce several antimicrobial factors; the most abundant are lysozyme and lactoferrin. Despite their likely importance in preventing infection, and their possible key role in the pathogenesis of cystic fibrosis (CF), we know little about their antibacterial activity in the context of the CF airway. We found that abundant airway antimicrobial factors kill common CF pathogens, although Burkholderia was relatively resistant. To study the antibacterial activity, we developed a rapid, sensitive, and quantitative in vitro luminescence assay. Because NaCl concentrations may be elevated in CF airway surface liquid, we tested the effect of salt on antibacterial activity. Activity of individual factors and of airway lavage fluid was inhibited by high ionic strength, and it was particularly sensitive to divalent cations. However, it was not inhibited by nonionic osmolytes and thus did not require hypotonic liquid. The inhibition by ionic strength could be partially compensated by increased concentrations of antibacterial factors, thus there was no one unique salt concentration for inhibition. CF airway secretions also contain abundant mucin and elastase; however, these had no effect on antibacterial activity of lysozyme, lactoferrin, or airway lavage fluids. When studied at low NaCl concentrations, CF and non-CF airway lavage fluids contained similar levels of antibacterial activity. These results suggest approaches toward developing treatments aimed at preventing or reducing airway infections in individuals with CF. PMID:10226057

  1. Role of platelets in allergic airway inflammation.

    PubMed

    Idzko, Marco; Pitchford, Simon; Page, Clive

    2015-06-01

    Increasing evidence suggests an important role for platelets and their products (e.g., platelet factor 4, β-thromboglobulin, RANTES, thromboxane, or serotonin) in the pathogenesis of allergic diseases. A variety of changes in platelet function have been observed in patients with asthma, such as alterations in platelet secretion, expression of surface molecules, aggregation, and adhesion. Moreover, platelets have been found to actively contribute to most of the characteristic features of asthma, including bronchial hyperresponsiveness, bronchoconstriction, airway inflammation, and airway remodeling. This review brings together the current available data from both experimental and clinical studies that have investigated the role of platelets in allergic airway inflammation and asthma. It is anticipated that a better understanding of the role of platelets in the pathogenesis of asthma might lead to novel promising therapeutic approaches in the treatment of allergic airway diseases. PMID:26051948

  2. Tumor Necrosis Factor Alpha Inhibits L-Type Ca2+ Channels in Sensitized Guinea Pig Airway Smooth Muscle through ERK 1/2 Pathway

    PubMed Central

    Reyes-García, Jorge; Flores-Soto, Edgar; Solís-Chagoyán, Héctor; Sommer, Bettina; Díaz-Hernández, Verónica; García-Hernández, Luz María

    2016-01-01

    Tumor necrosis factor alpha (TNF-α) is a potent proinflammatory cytokine that plays a significant role in the pathogenesis of asthma by inducing hyperresponsiveness and airway remodeling. TNF-α diminishes the L-type voltage dependent Ca2+ channel (L-VDCC) current in cardiac myocytes, an observation that seems paradoxical. In guinea pig sensitized tracheas KCl responses were lower than in control tissues. Serum from sensitized animals (Ser-S) induced the same phenomenon. In tracheal myocytes from nonsensitized (NS) and sensitized (S) guinea pigs, an L-VDCC current (ICa) was observed and diminished by Ser-S. The same decrease was detected in NS myocytes incubated with TNF-α, pointing out that this cytokine might be present in Ser-S. We observed that a small-molecule inhibitor of TNF-α (SMI-TNF) and a TNF-α receptor 1 (TNFR1) antagonist (WP9QY) reversed ICa decrease induced by Ser-S in NS myocytes, confirming the former hypothesis. U0126 (a blocker of ERK 1/2 kinase) also reverted the decrease in ICa. Neither cycloheximide (a protein synthesis inhibitor) nor actinomycin D (a transcription inhibitor) showed any effect on the TNF-α-induced ICa reduction. We found that CaV1.2 and CaV1.3 mRNA and proteins were expressed in tracheal myocytes and that sensitization did not modify them. In cardiac myocytes, ERK 1/2 phosphorylates two sites of the L-VDCC, augmenting or decreasing ICa; we postulate that, in guinea pig tracheal smooth muscle, TNF-α diminishes ICa probably by phosphorylating the L-VDCC site that reduces its activity through the ERK1/2 MAP kinase pathway. PMID:27445440

  3. Tumor Necrosis Factor Alpha Inhibits L-Type Ca(2+) Channels in Sensitized Guinea Pig Airway Smooth Muscle through ERK 1/2 Pathway.

    PubMed

    Reyes-García, Jorge; Flores-Soto, Edgar; Solís-Chagoyán, Héctor; Sommer, Bettina; Díaz-Hernández, Verónica; García-Hernández, Luz María; Montaño, Luis M

    2016-01-01

    Tumor necrosis factor alpha (TNF-α) is a potent proinflammatory cytokine that plays a significant role in the pathogenesis of asthma by inducing hyperresponsiveness and airway remodeling. TNF-α diminishes the L-type voltage dependent Ca(2+) channel (L-VDCC) current in cardiac myocytes, an observation that seems paradoxical. In guinea pig sensitized tracheas KCl responses were lower than in control tissues. Serum from sensitized animals (Ser-S) induced the same phenomenon. In tracheal myocytes from nonsensitized (NS) and sensitized (S) guinea pigs, an L-VDCC current (ICa) was observed and diminished by Ser-S. The same decrease was detected in NS myocytes incubated with TNF-α, pointing out that this cytokine might be present in Ser-S. We observed that a small-molecule inhibitor of TNF-α (SMI-TNF) and a TNF-α receptor 1 (TNFR1) antagonist (WP9QY) reversed ICa decrease induced by Ser-S in NS myocytes, confirming the former hypothesis. U0126 (a blocker of ERK 1/2 kinase) also reverted the decrease in ICa. Neither cycloheximide (a protein synthesis inhibitor) nor actinomycin D (a transcription inhibitor) showed any effect on the TNF-α-induced ICa reduction. We found that CaV1.2 and CaV1.3 mRNA and proteins were expressed in tracheal myocytes and that sensitization did not modify them. In cardiac myocytes, ERK 1/2 phosphorylates two sites of the L-VDCC, augmenting or decreasing ICa; we postulate that, in guinea pig tracheal smooth muscle, TNF-α diminishes ICa probably by phosphorylating the L-VDCC site that reduces its activity through the ERK1/2 MAP kinase pathway. PMID:27445440

  4. Impact of CPAP interface and mandibular advancement device on upper airway mechanical properties assessed with phrenic nerve stimulation in sleep apnea patients.

    PubMed

    Borel, Jean-Christian; Gakwaya, Simon; Masse, Jean-François; Melo-Silva, Cesar Augusto; Sériès, Frédéric

    2012-08-15

    Oronasal mask (ONM) can be used when mouth leaks impair nasal-CPAP effectiveness. However, ONM's constraint on the chin and straps' traction may alter upper airway (UA) mechanical properties. In contrast, mandibular advancement device associated with nasal-CPAP (NM+MAD) may reduce UA resistance. The aim of this exploratory study was to compare the effects of ONM, NM, and NM+MAD on UA mechanical properties. The three interface modalities were assessed in 11 OSAS patients at 6, 8, 10 cmH(2)O CPAP using a phrenic nerve magnetic stimulation (PNMS) protocol. PNMS-twitches' related flow, pharyngeal pressures (nasopharynx, velopharynx, oropharynx) and UA resistances were determined. Regardless of CPAP level, twitch-induced maximum flow was higher with NM+MAD than with ONM. Velopharyngeal resistance was higher with ONM than with NM+MAD. Oropharyngeal resistance was higher with ONM than with NM. In conclusion, NM+MAD reduced velopharyngeal resistance compared to those measured with ONM and NM alone. We hypothesize that this strategy may help reducing the effective pressure level and thus further limit the risk for mouth leaks. PMID:22772315

  5. Brachycephalic airway syndrome: management.

    PubMed

    Lodato, Dena L; Hedlund, Cheryl S

    2012-08-01

    Brachycephalic airway syndrome (BAS) is a group of primary and secondary abnormalities that result in upper airway obstruction. Several of these abnormalities can be addressed medically and/or surgically to improve quality of life. This article reviews potential complications, anesthetic considerations, recovery strategies, and outcomes associated with medical and surgical management of BAS. PMID:22935992

  6. Controversies in Pediatric Perioperative Airways

    PubMed Central

    Klučka, Jozef; Štourač, Petr; Štoudek, Roman; Ťoukálková, Michaela; Harazim, Hana; Kosinová, Martina

    2015-01-01

    Pediatric airway management is a challenge in routine anesthesia practice. Any airway-related complication due to improper procedure can have catastrophic consequences in pediatric patients. The authors reviewed the current relevant literature using the following data bases: Google Scholar, PubMed, Medline (OVID SP), and Dynamed, and the following keywords: Airway/s, Children, Pediatric, Difficult Airways, and Controversies. From a summary of the data, we identified several controversies: difficult airway prediction, difficult airway management, cuffed versus uncuffed endotracheal tubes for securing pediatric airways, rapid sequence induction (RSI), laryngeal mask versus endotracheal tube, and extubation timing. The data show that pediatric anesthesia practice in perioperative airway management is currently lacking the strong evidence-based medicine (EBM) data that is available for adult subpopulations. A number of procedural steps in airway management are derived only from adult populations. However, the objective is the same irrespective of patient age: proper securing of the airway and oxygenation of the patient. PMID:26759809

  7. Expansive Generation of Functional Airway Epithelium From Human Embryonic Stem Cells

    PubMed Central

    McIntyre, Brendan A.S.; Alev, Cantas; Mechael, Rami; Salci, Kyle R.; Lee, Jung Bok; Fiebig-Comyn, Aline; Guezguez, Borhane; Wu, Yuping; Sheng, Guojun

    2014-01-01

    Production of human embryonic stem cell (hESC)-derived lung progenitors has broad applicability for drug screening and cell therapy; however, this is complicated by limitations in demarcating phenotypic changes with functional validation of airway cell types. In this paper, we reveal the potential of hESCs to produce multipotent lung progenitors using a combined growth factor and physical culture approach, guided by the use of novel markers LIFRα and NRP1. Lung specification of hESCs was achieved by priming differentiation via matrix-specific support, followed by air-liquid interface to allow generation of lung progenitors capable of in vitro maturation into airway epithelial cell types, resulting in functional characteristics such as secretion of pulmonary surfactant, ciliation, polarization, and acquisition of innate immune activity. This approach provided a robust expansion of lung progenitors, allowing in vivo assessment, which demonstrated that only fully differentiated hESC-derived airway cells were retained in the distal airway, where they aided in physiological recovery in immunocompromised mice receiving airway injury. Our study provides a basis for translational applications of hESCs for lung diseases. PMID:24300555

  8. Factoring AAVE into Reading Assessment and Instruction

    ERIC Educational Resources Information Center

    Wheeler, Rebecca; Cartwright, Kelly B.; Swords, Rachel

    2012-01-01

    In our increasingly diverse schools, students bring diverse ways of speaking to the classroom. In turn, as features from students' home language varieties transfer into their readings of texts, teachers' assessment and intervention plans may be directly affected. If teachers conflate dialect influence with reading error in Standard English, they…

  9. Regulation of Airway Mucin Gene Expression

    PubMed Central

    Thai, Philip; Loukoianov, Artem; Wachi, Shinichiro; Wu, Reen

    2015-01-01

    Mucins are important components that exert a variety of functions in cell-cell interaction, epidermal growth factor receptor signaling, and airways protection. In the conducting airways of the lungs, mucins are the major contributor to the viscoelastic property of mucous secretion, which is the major barrier to trapping inhaled microbial organism, particulates, and oxidative pollutants. The homeostasis of mucin production is an important feature in conducting airways for the maintenance of mucociliary function. Aberrant mucin secretion and accumulation in airway lumen are clinical hallmarks associated with various lung diseases, such as asthma, chronic obstructive pulmonary disease, cystic fibrosis, emphysema, and lung cancer. Among 20 known mucin genes identified, 11 of them have been verified at either the mRNA and/or protein level in airways. The regulation of mucin genes is complicated, as are the mediators and signaling pathways. This review summarizes the current view on the mediators, the signaling pathways, and the transcriptional units that are involved in the regulation of airway mucin gene expression. In addition, we also point out essential features of epigenetic mechanisms for the regulation of these genes. PMID:17961085

  10. Cigarette smoke inhalation and the acute airway response.

    PubMed Central

    Higenbottam, T; Feyeraband, C; Clark, T J

    1980-01-01

    The acute airway response to smoking varying numbers (one to four) of identical cigarettes in rapid succession and smoking single cigarettes of differing tar/nicotine yields was assessed repeatedly in 13 healthy smokers. The airway response was variable, indicating airway narrowing consistently in only three subjects. There appeared no difference between forced spirometry and measurement of airway resistance in detecting the airway response. No relationship was observed between the airway response and amount of smoke inhaled into the lungs as measured either by changes in venous blood nicotine or percentage carboxyhaemoglobin. When five smokers inhaled smoke directly from a cigarette acute airway narrowing was consistently observed. A normal smoking pattern consisting of an initial drag of smoke into the mouth, followed after a pause by inhalation of smoke diluted with air, did not consistently cause airway narrowing although similar amounts of smoke as the direct drag were inhaled as assessed by changes in venous blood nicotine. The manner of smoke inhalation affects the relative concentrations of the different constituents of smoke reaching the lungs and also appears to be the main determinant of the acute airway response to smoking, which was unrelated to the number of cigarettes smoked or the tar content of the smoke. This suggests that patterns of smoke inhalation may influence the pathogenesis of bronchial disease associated with smoking. PMID:7434266

  11. Colonization of CF patients' upper airways with S. aureus contributes more decisively to upper airway inflammation than P. aeruginosa.

    PubMed

    Janhsen, Wibke Katharina; Arnold, Christin; Hentschel, Julia; Lehmann, Thomas; Pfister, Wolfgang; Baier, Michael; Böer, Klas; Hünniger, Kerstin; Kurzai, Oliver; Hipler, Uta-Christina; Mainz, Jochen Georg

    2016-10-01

    In cystic fibrosis (CF) patients' airways, inflammatory processes decisively contribute to remodeling and pulmonary destruction. The aims of this study were to compare upper airway (UAW) inflammation in the context of Staphylococcus aureus and Pseudomonas aeruginosa colonization in a longitudinal setting, and to examine further factors influencing UAW inflammation. Therefore, we analyzed soluble inflammatory mediators in noninvasively obtained nasal lavage (NL) of CF patients together with microbiology, medication, and relevant clinical parameters. NL, applying 10 mL of isotonic saline per nostril, was serially performed in 74 CF patients (326 samples). Concentrations of the inflammatory mediators' interleukin (IL)-1β, IL-6, IL-8, matrix metalloproteinase (MMP)-9, and its anti-protease TIMP-1 were quantified by bead-based multiplexed assay, neutrophil elastase (NE) via ELISA. Culture-based microbiology of the upper and lower airways (LAW), as well as serological and clinical findings, were compiled. Our results indicate that UAW colonization with S. aureus significantly impacts the concentration of all measured inflammatory mediators in NL fluid except TIMP-1, whereas these effects were not significant for P. aeruginosa. Patients with S. aureus colonization of both the UAW and LAW showed significantly increased concentrations of IL-1β, IL-6, IL-8, MMP-9, and slightly elevated concentrations of NE in NL fluid compared to non-colonized patients. This work elaborates a survey on S. aureus' virulence factors that may contribute to this underestimated pathology. Serial assessment of epithelial lining fluid by NL reveals that colonization of the UAW with S. aureus contributes more to CF airway inflammatory processes than hitherto expected. PMID:27377929

  12. Development of an integral assessment approach of health status in patients with obstructive airway diseases: the CORONA study

    PubMed Central

    van den Akker, Edmée FMM; van ‘t Hul, Alex J; Chavannes, Niels H; Braunstahl, Gert-Jan; van Bruggen, Alie; Rutten-van Mölken, Maureen PMH; in ‘t Veen, Johannes CCM

    2015-01-01

    Background Traditional assessment of patients with obstructive lung diseases (asthma and chronic obstructive pulmonary disease; COPD) relies on physiological tests. The COPD and Asthma Rotterdam Integrated Care Approach (CORONA) study aims to develop a diagnostic pathway with a more comprehensive approach to the assessment of patients with asthma and COPD in secondary care. Methods An eight-step method was used to develop and implement the pathway for patients with asthma or COPD referred to an outpatient hospital setting. Results The diagnostic pathway consists of an evidence-based set of measurements prioritized by a Delphi procedure. The pathway incorporates three innovative diagnostics: the metronome-paced hyperventilation test to measure dynamic hyperinflation, an activity monitor to objectively evaluate physical activity in daily life, and the Nijmegen Clinical Screening Instrument as a comprehensive assessment tool to acquire detailed insight into symptoms, functional limitations, and quality of life. Conclusion An innovative diagnostic pathway was developed and implemented for patients with obstructive lung diseases referred to secondary care. As this pathway aims to provide a comprehensive analysis of health status, it focuses on biomedical aspects and also reviews behavioral aspects that further elucidate the patient’s health status. The added value of the diagnostic pathway needs to be determined from both an organizational perspective and from the individual patient’s viewpoint. PMID:26609228

  13. ASSESSING EXPOSURE FACTORS OF ASTHMATIC CHILDREN

    EPA Science Inventory

    Since 1980, there has been a 75% increase in the prevalence of asthma in children in the U.S.

    A pilot study was conducted in a southeastern US city to develop and to evaluate methods and factors associated with asthmatic children's (< 6 yrs.) exposures to air pollutants. ...

  14. Assessing Teacher Manageability: A Factor Analytic Approach.

    ERIC Educational Resources Information Center

    Safran, Stephen P.; And Others

    1988-01-01

    This study analyzed 182 educators' beliefs about their ability to manage maladaptive classroom behaviors. A factor analysis of teacher manageability ratings demonstrated that, by changing the method used to group behaviors, the structure of a teacher checklist also changes. The most difficult behavior to manage was "lack of communication."…

  15. Overexpression of Smad2 Drives House Dust Mite–mediated Airway Remodeling and Airway Hyperresponsiveness via Activin and IL-25

    PubMed Central

    Gregory, Lisa G.; Mathie, Sara A.; Walker, Simone A.; Pegorier, Sophie; Jones, Carla P.; Lloyd, Clare M.

    2010-01-01

    Rationale: Airway hyperreactivity and remodeling are characteristic features of asthma. Interactions between the airway epithelium and environmental allergens are believed to be important in driving development of pathology, particularly because altered epithelial gene expression is common in individuals with asthma. Objectives: To investigate the interactions between a modified airway epithelium and a common aeroallergen in vivo. Methods: We used an adenoviral vector to generate mice overexpressing the transforming growth factor-β signaling molecule, Smad2, in the airway epithelium and exposed them to house dust mite (HDM) extract intranasally. Measurements and Main Results: Smad2 overexpression resulted in enhanced airway hyperreactivity after allergen challenge concomitant with changes in airway remodeling. Subepithelial collagen deposition was increased and smooth muscle hyperplasia was evident resulting in thickening of the airway smooth muscle layer. However, there was no increase in airway inflammation in mice given the Smad2 vector compared with the control vector. Enhanced airway hyperreactivity and remodeling did not correlate with elevated levels of Th2 cytokines, such as IL-13 or IL-4. However, mice overexpressing Smad2 in the airway epithelium showed significantly enhanced levels of IL-25 and activin A after HDM exposure. Blocking activin A with a neutralizing antibody prevented the increase in lung IL-25 and inhibited subsequent collagen deposition and also the enhanced airway hyperreactivity observed in the Smad2 overexpressing HDM-exposed mice. Conclusions: Epithelial overexpression of Smad2 can specifically alter airway hyperreactivity and remodeling in response to an aeroallergen. Moreover, we have identified novel roles for IL-25 and activin A in driving airway hyperreactivity and remodeling. PMID:20339149

  16. The Three A's in Asthma - Airway Smooth Muscle, Airway Remodeling & Angiogenesis.

    PubMed

    Keglowich, L F; Borger, P

    2015-01-01

    Asthma affects more than 300 million people worldwide and its prevalence is still rising. Acute asthma attacks are characterized by severe symptoms such as breathlessness, wheezing, tightness of the chest, and coughing, which may lead to hospitalization or death. Besides the acute symptoms, asthma is characterized by persistent airway inflammation and airway wall remodeling. The term airway wall remodeling summarizes the structural changes in the airway wall: epithelial cell shedding, goblet cell hyperplasia, hyperplasia and hypertrophy of the airway smooth muscle (ASM) bundles, basement membrane thickening and increased vascular density. Airway wall remodeling starts early in the pathogenesis of asthma and today it is suggested that remodeling is a prerequisite for other asthma pathologies. The beneficial effect of bronchial thermoplasty in reducing asthma symptoms, together with the increased potential of ASM cells of asthmatics to produce inflammatory and angiogenic factors, indicate that the ASM cell is a major effector cell in the pathology of asthma. In the present review we discuss the ASM cell and its role in airway wall remodeling and angiogenesis. PMID:26106455

  17. The Three A’s in Asthma – Airway Smooth Muscle, Airway Remodeling & Angiogenesis

    PubMed Central

    Keglowich, L.F; Borger, P

    2015-01-01

    Asthma affects more than 300 million people worldwide and its prevalence is still rising. Acute asthma attacks are characterized by severe symptoms such as breathlessness, wheezing, tightness of the chest, and coughing, which may lead to hospitalization or death. Besides the acute symptoms, asthma is characterized by persistent airway inflammation and airway wall remodeling. The term airway wall remodeling summarizes the structural changes in the airway wall: epithelial cell shedding, goblet cell hyperplasia, hyperplasia and hypertrophy of the airway smooth muscle (ASM) bundles, basement membrane thickening and increased vascular density. Airway wall remodeling starts early in the pathogenesis of asthma and today it is suggested that remodeling is a prerequisite for other asthma pathologies. The beneficial effect of bronchial thermoplasty in reducing asthma symptoms, together with the increased potential of ASM cells of asthmatics to produce inflammatory and angiogenic factors, indicate that the ASM cell is a major effector cell in the pathology of asthma. In the present review we discuss the ASM cell and its role in airway wall remodeling and angiogenesis. PMID:26106455

  18. CD38 and Airway hyperresponsiveness: Studies on human airway smooth muscle cells and mouse models

    PubMed Central

    Guedes, Alonso GP; Deshpande, Deepak A; Dileepan, Mythili; Walseth, Timothy F; Panettieri, Reynold A; Subramanian, Subbaya; Kannan, Mathur S

    2015-01-01

    Asthma is an inflammatory disease in which altered calcium regulation, contractility and airway smooth muscle (ASM) proliferation contribute to airway hyperresponsiveness and airway wall remodeling. The enzymatic activity of CD38, a cell-surface protein expressed in human ASM cells, generates calcium mobilizing second messenger molecules such as cyclic ADP-ribose. CD38 expression in human ASM cells is augmented by cytokines (e.g. TNF-α) that requires activation of MAP kinases and the transcription factors, NF-ƙB and AP-1 and post-transcriptionally regulated by miR-140-3p and miR-708 by binding to 3’ Untranslated Region of CD38 as well as by modulating the activation of signaling mechanisms involved in its regulation. Mice deficient in CD38 exhibit reduced airway responsiveness to inhaled methacholine relative to response in wild-type mice. Intranasal challenge of CD38 deficient mice with TNF-α or IL-13, or the environmental fungus Alternaria alternata, causes significantly attenuated methacholine responsiveness compared to wild-type mice, with comparable airway inflammation. Reciprocal bone marrow transfer studies revealed partial restoration of airway hyperresponsiveness to inhaled methacholine in the Cd38 deficient mice. These studies provide evidence for CD38 involvement in the development of airway hyperresponsiveness, a hallmark feature of asthma. Future studies aimed at drug discovery and delivery targeting CD38 expression and/or activity are warranted. PMID:25594684

  19. Airway dysfunction in swimmers.

    PubMed

    Bougault, Valérie; Boulet, Louis-Philippe

    2012-05-01

    Elite competitive swimmers are particularly affected by airway disorders that are probably related to regular and intense training sessions in a chlorinated environment. Upper and lower airway respiratory symptoms, rhinitis, airway hyper-responsiveness, and exercise-induced bronchoconstriction are highly prevalent in these athletes, but their influence on athletic performance is still unclear. The authors reviewed the main upper and lower respiratory ailments observed in competitive swimmers who train in indoor swimming pools, their pathophysiology, clinical significance and possible effects on performance. Issues regarding the screening of these disorders, their management and preventive measures are addressed. PMID:22247299

  20. Macrophage adaptation in airway inflammatory resolution.

    PubMed

    Kaur, Manminder; Bell, Thomas; Salek-Ardakani, Samira; Hussell, Tracy

    2015-09-01

    Bacterial and viral infections (exacerbations) are particularly problematic in those with underlying respiratory disease, including post-viral infection, asthma, chronic obstructive pulmonary disease and pulmonary fibrosis. Patients experiencing exacerbations tend to be at the more severe end of the disease spectrum and are often difficult to treat. Most of the unmet medical need remains in this patient group. Airway macrophages are one of the first cell populations to encounter airborne pathogens and, in health, exist in a state of reduced responsiveness due to interactions with the respiratory epithelium and specific factors found in the airway lumen. Granulocyte-macrophage colony-stimulating factor, interleukin-10, transforming growth factor-β, surfactant proteins and signalling via the CD200 receptor, for example, all raise the threshold above which airway macrophages can be activated. We highlight that following severe respiratory inflammation, the airspace microenvironment does not automatically re-set to baseline and may leave airway macrophages more restrained than they were at the outset. This excessive restraint is mediated in part by the clearance of apoptotic cells and components of extracellular matrix. This implies that one strategy to combat respiratory exacerbations would be to retune airway macrophage responsiveness to allow earlier bacterial recognition. PMID:26324813

  1. Prognosis and Risk Factors for Congenital Airway Anomalies in Children with Congenital Heart Disease: A Nationwide Population-Based Study in Taiwan

    PubMed Central

    Lee, Yu-Sheng; Jeng, Mei-Jy; Tsao, Pei-Chen

    2015-01-01

    Background The mortality risk associated with congenital airway anomalies (CAA) in children with congenital heart disease (CHD) is unclear. This study aimed to investigate the factors associated with CAA, and the associated mortality risk, among children with CHD. Methods This nationwide, population-based study evaluated 39,652 children with CHD aged 0–5 years between 2000 and 2011, using the Taiwan National Health Insurance Research Database (NHIRD). We performed descriptive, logistic regression, Kaplan–Meier, and Cox regression analyses of the data. Results Among the children with CHD, 1,591 (4.0%) had concomitant CAA. Children with CHD had an increased likelihood of CAA if they were boys (odds ratio [OR], 1.48; 95% confidence interval [CI], 1.33–1.64), infants (OR, 5.42; 95%CI, 4.06–7.24), or had a congenital musculoskeletal anomaly (OR, 3.19; 95%CI, 2.67–3.81), and were typically identified 0–3 years after CHD diagnosis (OR, 1.33; 95%CI 1.17–1.51). The mortality risk was increased in children with CHD and CAA (crude hazard ratio [HR], 2.05; 95%CI, 1.77–2.37), even after adjusting for confounders (adjusted HR, 1.76; 95%CI, 1.51–2.04). Mortality risk also changed by age and sex (adjusted HR and 95%CI are quoted): neonates, infants, and toddlers and preschool children, 1.67 (1.40–2.00), 1.93 (1.47–2.55), and 4.77 (1.39–16.44), respectively; and boys and girls, 1.62 (1.32–1.98) and 2.01 (1.61–2.50), respectively. Conclusion The mortality risk is significantly increased among children with CHD and comorbid CAA. Clinicians should actively seek CAA during the follow-up of children with CHD. PMID:26334302

  2. Factors influencing the assessment of treatment needs.

    PubMed

    Gjermo, P

    1991-07-01

    Epidemiologic surveys have provided data for health planning by estimating prevalence and incidence of diseases in populations. New ways of presenting epidemiologic data on periodontal diseases have changed our understanding of their extent and severity, and conversion of prevalence data into treatment need estimates has proved difficult. Furthermore, new concepts of the pathogenesis of periodontal diseases have questioned the validity of epidemiologic methods currently used. Treatment need assessments vary considerably between studies even when prevalence data from the same populations are similar. This may be due to lack of described goals for periodontal health. Various aspects of the concept of need for treatment are discussed. It is suggested that periodontal treatment need on a population level is defined as the intervention needed in order to change the existing periodontal condition to the described goal. Thus, treatment need assessments will have to include descriptive epidemiologic data as well as defined periodontal health goals. It is recommended that goals are described in terms compatible with the indicators used in the epidemiologic description of the disease status. PMID:1890213

  3. Anthropometric Assessment of Neck Adipose Tissue and Airway Volume Using Multidetector Computed Tomography: An Imaging Approach and Association With Overall Mortality.

    PubMed

    Maresky, Hillel S; Sharfman, Zachary; Ziv-Baran, Tomer; Gomori, J M; Copel, Laurian; Tal, Sigal

    2015-11-01

    Neck adiposity tissue volume (NATV) accumulation is an indicator for metabolic syndrome and cardiovascular disease (CVD). Neck circumference is a poor measure of NATV, and a quantifier for this entity has not yet been established. To evaluate volumetric quantification by multidetector computed tomography (MDCT) as a reproducible anthropometric tool to measure NATV and airway volume (AWV). A total of 519 patients, including a subset of 70 random patients who underwent head and neck CT scanning in our hospital within 1 year (2013), were studied. Included patients were all those undergoing nonenhanced CT (NECT) or CT angiography (CTA). Neck cross-sectional areas (NCSA) were measured at 2 separate levels of the neck, and 3D postprocessing tissue reconstruction was performed, and NATV and AWVs were quantified volumetrically for all patients within the year. The average NCSA at the level of the soft palate and thyroid cartilage was 22,579 and 14,500 mm, respectively. NATV when compared to the upper and lower levels of NCSA showed correlations of 0.64 and 0.79, respectively (P < 0.001). Interobserver analysis showed mean deviations of 0.46% and 0.32% for NATV and AWV, respectively. A strong correlation between NATV and body mass index (BMI) was found (r = 0.658, P < 0.001), and the top quartile of NATV:AWV patients (out of 519 patients) displayed a statistically significant mortality rate during 670 days of follow-up (d = 7.5%, P = 0.032). After adjustment for age and gender, the association between NATV:AWV and mortality was close to significant (P = 0.072). Volumetric quantification of NATV and AWV is a reproducible and prognostic anthropometric tool, as a high NATV:AWV demonstrated a significant risk factor for mortality; future research may further advance our understanding of this phenomenon. PMID:26559286

  4. Bronchial hyperreactivity is correlated with increased baseline airway tone.

    PubMed

    Bergner, A; Kellner, J; Kemp da Silva, A; Fischer, R; Gamarra, F; Huber, R M

    2006-02-21

    Physiologically, airways are not completely relaxed but maintain a baseline airway tone (BAT). Although not fulfilling the criteria for obstructive airway disease, increased BAT may nevertheless be important because the same amount of airway narrowing can be well tolerated or can cause severe airway obstruction depending on the starting point of the narrowing. In this study, we aimed at studying if BAT is correlated with bronchial hyperreactivity (BHR). For in vitro studies, airways in murine lung slices were digitally recorded and the change in cross-sectional area with time was quantified. BAT was measured by the amount of relaxation induced by permeabilization of the cell membrane with beta-escin in zero external calcium. BHR was induced by incubation of lung slices with interleukin-13 (IL-13). T-bet knock-out mice served as an additional model for BHR. T-bet knock-out mice show a shift towards TH2-lymphocytes and display histological as well as functional characteristics of asthma. In vivo, the specific airway resistance of healthy non-smoking volunteers was assessed before and after inhalation of formoterol and bronchial challenge was performed using methacholin. In murine lung slices that had been cultivated without serum, only a minimal BAT could be observed. But, after cultivation with 10 % new born calve serum, airways showed a BAT of approximately 13 % that could be reduced by incubation with an IL-13 receptor antagonist. Atropine, isoproterenol and indomethacin failed to relax airways regardless of cultivation with serum. Incubation of lung slices without serum but with IL-13 increased BAT as well as airway responsiveness to acetylcholine and both effects were more pronounced in small compared to large airways. In lung slices from T-bet knock-out mice, airways were hyperreactive compared to airways in slices from wild type mice and BAT was found to be increased. Again, both effects were more pronounced in small compared to large airways. In human non

  5. Assessing Poverty and Related Factors in Turkey

    PubMed Central

    Saatci, Esra; Akpinar, Ersin

    2007-01-01

    Poverty, a complex, multidimensional, and universal problem, has been conceptualized as income and material deprivation. In this article, we discuss poverty and related factors in Turkey. The absolute poverty line for Turkey was US $4 per capita per day. Turkey was ranked 92nd out of 177 countries with moderate human development in the 2006 Human Development Report. The individual food poverty rate was 1.35% and the non-food poverty rate was 25.6%. The highest poverty rate was among primary school graduates (42.5%; 38.5% for women and 46.8% for men). The rate for this group was higher in urban than in rural areas. Among poor people, 57.2% were married. The highest poverty rate was among agricultural workers (46.6%) and in Eastern and Southeastern Anatolia. Factors related to poverty were crowded households, unemployment, immigration, working for a daily wage in the agricultural and construction sector, low educational status, female sex or married status, lacking social insurance, and living in rural areas or in Eastern and Southeastern Anatolia. PMID:17948949

  6. Assessing poverty and related factors in Turkey.

    PubMed

    Saatci, Esra; Akpinar, Ersin

    2007-10-01

    Poverty, a complex, multidimensional, and universal problem, has been conceptualized as income and material deprivation. In this article, we discuss poverty and related factors in Turkey. The absolute poverty line for Turkey was US$ 4 per capita per day. Turkey was ranked 92nd out of 177 countries with moderate human development in the 2006 Human Development Report. The individual food poverty rate was 1.35% and the non-food poverty rate was 25.6%. The highest poverty rate was among primary school graduates (42.5%; 38.5% for women and 46.8% for men). The rate for this group was higher in urban than in rural areas. Among poor people, 57.2% were married. The highest poverty rate was among agricultural workers (46.6%) and in Eastern and Southeastern Anatolia. Factors related to poverty were crowded households, unemployment, immigration, working for a daily wage in the agricultural and construction sector, low educational status, female sex or married status, lacking social insurance, and living in rural areas or in Eastern and Southeastern Anatolia. PMID:17948949

  7. Airway management in trauma.

    PubMed

    Langeron, O; Birenbaum, A; Amour, J

    2009-05-01

    Maintenance of a patent and prevention of aspiration are essential for the management of the trauma patient, that requires experienced physicians in airway control techniques. Difficulties of the airway control in the trauma setting are increased by the vital failures, the risk of aspiration, the potential cervical spine injury, the combative patient, and the obvious risk of difficult tracheal intubation related to specific injury related to the trauma. Endotracheal intubation remains the gold standard in trauma patient airway management and should be performed via the oral route with a rapid sequence induction and a manual in-line stabilization maneuver, to decrease the risks previously mentioned. Different techniques to control the airway in trauma patients are presented: improvement of the laryngoscopic vision, lighted stylet tracheal intubation, retrograde technique for orotracheal intubation, the laryngeal mask and the intubating laryngeal mask airways, the combitube and cricothyroidotomy. Management of the airway in trauma patients requires regular training in these techniques and the knowledge of complementary techniques allowing tracheal intubation or oxygenation to overcome difficult intubation and to prevent major complications as hypoxemia and aspiration. PMID:19412149

  8. Factors in the assessment of suicidality in youth.

    PubMed

    Posner, Kelly; Melvin, Glenn A; Stanley, Barbara; Oquendo, Maria A; Gould, Madelyn

    2007-02-01

    Suicide remains a leading cause of death among youth, and suicide ideation and behavior are relatively common in both normal and clinical populations. Clinicians working with young people must assess for the presence of suicidal ideation, suicidal behavior, and other risk factors, in order to determine the level of risk. This paper provides the clinician with a summary of risk factors for youth suicide, as well as providing standardized terminology to enhance assessment of suicidal ideation and behavior. PMID:17277716

  9. Assessment of suitability of i-gel and laryngeal mask airway-supreme for controlled ventilation in anesthetized paralyzed patients: A prospective randomized trial

    PubMed Central

    Radhika, Kusuma Srividya; Sripriya, R.; Ravishankar, M.; Hemanth Kumar, V. R.; Jaya, V.; Parthasarathy, S.

    2016-01-01

    Context: Laryngeal mask airway supreme (LMA-S) has an inflatable cuff while i-gel has a noninflatable cuff made of thermoplastic elastomer. Aims: To study the efficacy of ventilation and the laryngeal seal pressures (LSPs) with either device. Our secondary objectives were to compare the ease of insertion, adequacy of positioning the device, hemodynamic response to device insertion, and any postoperative oropharyngeal morbidity. Settings and Design: A prospective, randomized, single-blinded study at Teaching Medical School in South India. Materials and Methods: Forty-two patients posted for surgery under general anesthesia were randomly divided into two groups - LMA-S and i-gel. After a standardized premedication and anesthesia induction sequence, the supra-glottic devices were introduced. Ease of insertion was assessed from the number of attempts taken to insert, insertion time, and any maneuvers required to insert the device. Position of the device was assessed by the ease of gastric catheter placement and the fibreoptic grading of laryngeal visualization. Efficacy of ventilation was determined from the LSP, peak inspiratory pressure (PIP), and end-tidal carbon dioxide (EtCO2)values. Any postoperative oropharyngeal morbidity was also recorded. Statistical Analysis: Descriptive analysis was reported as a mean and standard deviation, median, and range of continuous variables. Demographics were analyzed using a unpaired t-test for parametric data and Chi-square test for nonparametric data. Respiratory and hemodynamic data was analyzed using one-way ANOVA to find statistical difference within and between the two groups. Results: LMA-S was successfully inserted in 95% of patients and i-gel in 85.5% of patients. There was a significant difference (P = 0.021) in the LSPs between the two groups (18.15 cmH2O in LMA-S and 21.28 cmH2O in the i-gel group). There was no significant difference in the PIPs, leak fraction, and the EtCO2values. Conclusion: Both devices are

  10. [Exercise-induced airway obstruction in asthmatic children and adolescents].

    PubMed

    Zapletal, A; Zbojan, J; Pohanka, V

    1992-03-01

    In 115 asymptomatic asthmatic children and adolescents (age 6-18 years) there was studied the magnitude of airway obstruction, induced by various physical efforts and assessed from the recording of maximum expiratory flow-volume curves and in some patients by "specific" airway conductance measurement in a body plethysmograph. The effects of 5 minutes free running outdoors, 5 minutes of exercise on a bicycle ergometer (2 watts/kg of body weight), routine swimming training in swimming pool and of forced expiration maneuver on the magnitude of airway obstruction were assessed. The most frequent and largest degree of airway obstruction was observed after 5 min. free running outdoors (heart rate after running 160-200/min). The obstruction was revealed in 80-100% asthmatics in various groups. The chosen lung function parameters showed exercise-induced airway obstruction in the same patients in various proportions as well as the magnitude of the obstruction. Following free running outdoors the values of maximum expiratory flow at 25% of vital capacity and "specific" airway conductance were most reduced. Spontaneous retreat of obstruction was observed in the course of 2 hours. The physical exercise on a bicycle ergometer was a small stimulus in inducing of airway obstruction. The swimming in a pool did not provoke any obstruction. In 10% of our asthmatics airway obstruction was observed following forced expiration maneuver. Airway obstruction induced by 5 minutes free running outdoors and assessed best by flow-volume curves appeared as a suitable test in the assessment of airway hyperresponsiveness. PMID:1591810

  11. Factor Structure and Invariance across Gender of the Devereux Early Childhood Assessment Protective Factor Scale

    ERIC Educational Resources Information Center

    Ogg, Julia A.; Brinkman, Tara M.; Dedrick, Robert F.; Carlson, John S.

    2010-01-01

    Early childhood social-emotional assessment has traditionally focused on risk factors or psychopathology, and has less frequently examined protective factors that may serve to promote positive developmental outcomes for children. To advance conceptual models that include protective factors as key explanatory constructs, there is a need for…

  12. Vitamin D deficiency causes airway hyperresponsiveness, increases airway smooth muscle mass, and reduces TGF‐β expression in the lungs of female BALB/c mice

    PubMed Central

    Foong, Rachel E.; Shaw, Nicole C.; Berry, Luke J.; Hart, Prue H.; Gorman, Shelley; Zosky, Graeme R.

    2014-01-01

    Abstract Vitamin D deficiency is associated with disease severity in asthma. We tested whether there is a causal association between vitamin D deficiency, airway smooth muscle (ASM) mass, and the development of airway hyperresponsiveness (AHR). A physiologically relevant mouse model of vitamin D deficiency was developed by raising BALB/c mice on vitamin D‐deficient or ‐replete diets. AHR was assessed by measuring lung function responses to increasing doses of inhaled methacholine. Five‐micron sections from formalin‐fixed lungs were used for ASM measurement and assessment of lung structure using stereological methods. Transforming growth factor (TGF)‐β levels were measured in bronchoalveolar lavage fluid (BALF). Lungs were dissected from embryonic day (E) 17.5 vitamin D‐deficient and ‐replete fetal mice for quantification of ASM density and relative gene expression of TGF‐β signaling pathway molecules. Eight‐week‐old adult vitamin D‐deficient female mice had significantly increased airway resistance and ASM in the large airways compared with controls. Vitamin D‐deficient female mice had a smaller lung volume, volume of parenchyma, and alveolar septa. Both vitamin D‐deficient male and female mice had reduced TGF‐β levels in BALF. Vitamin D deficiency did not have an effect on ASM density in E17.5 mice, however, expression of TGF‐β1 and TGF‐β receptor I was downregulated in vitamin D‐deficient female fetal mice. Decreased expression of TGF‐β1 and TGF‐β receptor I during early lung development in vitamin D‐deficient mice may contribute to airway remodeling and AHR in vitamin D‐deficient adult female mice. This study provides a link between vitamin D deficiency and respiratory symptoms in chronic lung disease. PMID:24760528

  13. Assessment of environmental factors affecting male fertility.

    PubMed

    Dixon, R L; Sherins, R J; Lee, I P

    1979-06-01

    Exposure to drinking water containing as much as 500 ppm aluminum chloride for periods of 30, 60, and 90 days had no apparent effect on male reproductive processes. In an attempt to correlate enzyme activity with particular spermatogenic cell types, postnatal development of testicular enzymes was studied. Eight enzymes were selected: hyaluronidase (H), lactate dehydrogenase isoenzyme-X (LDH-X), dehydrogenases of sorbitol (SDH), alpha-glycerophosphate (GPDH), glucose-6-phosphate (G6PDH), malate (MDH), glyceraldehyde-3-phosphate (G3PDH), and isocitrate (ICDH). Enzyme specific activities in testicular homogenates were determined. Two types of enzyme developmental patterns were observed. One was represented by H, LDH-X, SDH, and GPDH; and the other by G6PDH, MDH, G3PDH, and ICDH. The former was characterized by a change in enzyme activities from low in newborn to high in adult while in the latter this pattern was reversed. The two complementary enzyme systems crossed each other at puberty. Prior to puberty, only spermatogonial cells are present; sperm differentiation initiated at puberty adds spermatocytes and spermatids to the testicular cell population. Male rats were exposed to borax in their diet for periods of 30 and 60 days. Concentrations of boron were 0, 500, 1000, and 2000 ppm. At the end of each experimental period, the specific activities of the selected enzymes were determined in the testis and prostate. Correlations of enzyme activity with testicular histology and androgen activities of the male accessory organs were sought. In addition, plasma FSH, LH, and testosterone levels were measured to assess pituitary-testicular interaction. Plasma and testicular boron concentrations were determined and a minimum boron concentration which induced germinal aplasia and male infertility was estimated. In both 30 and 60 day feeding studies, male rats receiving 500 ppm failed to demonstrate any significant adverse effects. In contrast, male rats receiving 100 and 2000

  14. A comparison of airway dimensions, measured by acoustic reflectometry and ultrasound before and after general anaesthesia.

    PubMed

    Ushiroda, J; Inoue, S; Kirita, T; Kawaguchi, M

    2014-12-01

    Changes in airway dimensions can occur during general anaesthesia and surgery for a variety of reasons. This study explored factors associated with postoperative changes in airway dimensions. Patient airway volume was measured by acoustic reflectometory and neck muscle diameter by ultrasound echography in the pre- and post-anaesthetic periods in a total of 281 patients. Neck circumference was also assessed during these periods. A significant decrease in median (IQR [range]) total airway volume (from 63.8 (51.8-75.7 [14.7-103]) ml to 45.9 (33.5-57.2 [6.4-96.3]) ml, p < 0.0001), and a significant increase in muscle diameter (from 4.3 (3.3-5.6 [2.2-9.0]) mm to 5.8 (4.7-7.3 [2.8-1.3]) mm, p < 0.0001) and neck circumference (from 34.0 (32.5-37.0 [29.5-49.0]) cm to 35.0 (33.5-38.0 [30.5-50.5]) cm, p < 0.0001) were observed. It may be possible that changes in airway volume and neck circumference were influenced by surgical duration or peri-operative fluid management (ρ) = -0.31 (95% CI -0.24 to -0.01), p = 0.0301, -0.17 (-0.23 to -0.06), p = 0.0038, 0.23 (0.12-0.34), p < 0.0001, and 0.16 (0.05-0.27), p = 0.0062, respectively). The intra-oral space can significantly decrease and neck thickness increase after general anaesthesia, and might increase the risk of difficult laryngoscopy and intubation if airway management is required after extubation following general anaesthesia. PMID:25123382

  15. O3-induced mucosa-linked airway muscle hyperresponsiveness in the guinea pig

    SciTech Connect

    Murlas, C.G.; Murphy, T.P.; Chodimella, V. )

    1990-07-01

    We investigated the effects of ozone exposure (3.0 ppm, 2 h) on the responsiveness of guinea pig airway muscle in vitro from animals developing bronchial hyperreactivity. Muscarinic reactivity in vivo was determined by measuring specific airway resistance (sRaw) in response to increasing concentrations of aerosolized acetylcholine (ACh) administered before and 30 min after exposure. Immediately after reactivity testing, multiple tracheal rings from ozone- and air-exposed animals were prepared and the contractile responses to increasing concentrations of substance P, ACh, or KCl were assessed in the presence of 10 microM indomethacin with or without 1 microM phosphoramidon, an inhibitor of neutral endopeptidase. Isometric force generation in vitro was measured on stimulation by cumulative concentrations of the agonists, and force generation (in g/cm2) was calculated after determination of muscle cross-sectional area. The smooth muscle of mucosa-intact airways from guinea pigs with ozone-induced bronchial hyper-reactivity proved to be hyperresponsive in vitro to substance P and ACh but not to KCl. Pretreatment with phosphoramidon abolished the increase in substance P responsiveness but had no effect on muscarinic hyperresponsiveness after ozone exposure. Furthermore, substance P responsiveness was not augmented in ozone-exposed airways in which the mucosa had been removed before testing in vitro. Likewise, muscarinic hyperresponsiveness was not present in ozone-exposed airways without mucosa. Our data indicate that airway smooth muscle responsiveness is increased in guinea pigs with ozone-induced bronchial hyperreactivity and suggest that this hyperresponsiveness may be linked to non-cyclooxygenase mucosa-derived factors.

  16. Mucociliary clearance, airway inflammation and nasal symptoms in urban motorcyclists

    PubMed Central

    Brant, Tereza C S; Yoshida, Carolina T; de S. Carvalho, Tomas; Nicola, Marina L; Martins, Jocimar A; Braga, Lays M; de Oliveira, Regiani C; Leyton, Vilma; de André, Carmen S; Saldiva, Paulo H N; Rubin, Bruce K; Nakagawa, Naomi K

    2014-01-01

    OBJECTIVES: There is evidence that outdoor workers exposed to high levels of air pollution exhibit airway inflammation and increased airway symptoms. We hypothesized that these workers would experience increased airway symptoms and decreased nasal mucociliary clearance associated with their exposure to air pollution. METHODS: In total, 25 non-smoking commercial motorcyclists, aged 18-44 years, were included in this study. These drivers work 8-12 hours per day, 5 days per week, driving on urban streets. Nasal mucociliary clearance was measured by the saccharine transit test; airway acidification was measured by assessing the pH of exhaled breath condensate; and airway symptoms were measured by the Sino-nasal Outcome Test-20 questionnaire. To assess personal air pollution exposure, the subjects used a passive-diffusion nitrogen dioxide (NO2) concentration-monitoring system during the 14 days before each assessment. The associations between NO2 and the airway outcomes were analyzed using the Mann-Whitney test and the Chi-Square test. Clinicaltrials.gov: NCT01976039. RESULTS: Compared with clearance in healthy adult males, mucociliary clearance was decreased in 32% of the motorcyclists. Additionally, 64% of the motorcyclists had airway acidification and 92% experienced airway symptoms. The median personal NO2 exposure level was 75 mg/m3 for these subjects and a significant association was observed between NO2 and impaired mucociliary clearance (p = 0.036). CONCLUSION: Non-smoking commercial motorcyclists exhibit increased airway symptoms and airway acidification as well as decreased nasal mucociliary clearance, all of which are significantly associated with the amount of exposure to air pollution. PMID:25628001

  17. Regional aerosol deposition in human upper airways

    SciTech Connect

    Swift, D.L.

    1992-11-01

    Laboratory experimental studies were carried out to investigate the factors influencing the deposition of aerosols ranging in size from 1 nm to 10 [mu]m in the human nasal, oral, pharyngeal and laryngeal airways. These experimental studies were performed in replicate upper airway physical models and in human volunteer subjects. New replicate models of the oral passage of an infant, the oral passage of an adult at two openings and the combined nasal and oral airways of an adult were constructed during the period, adding to the existing models of adult, child and infant nasal and oral airways models. Deposition studies in the adult oral and adult nasal models were performed under simulated cyclic flow conditions with 1 nm particles to compare with previously measured constant flow studies. Similar studies with inertial particles (1--10 [mu]m diameter) were performed with the adult nasal model; in both instances, results with cyclic flow were similar to constant flow results using a simple average flow rate based on inspiratory volume and time of inspiration. Human subject studies were performed with particle sizes 5--20 nm for nasal inspiration; preliminary analysis shows good agreement with model studies at several representative flow rates. Nasal inspiratory inertial deposition of 1--4 [mu]m diameter particles was measured in several adults as a function of airway dimensions; dimensional changes of the valve area by decongestion did not produce concomitant deposition changes.

  18. Silibinin attenuates allergic airway inflammation in mice

    SciTech Connect

    Choi, Yun Ho; Jin, Guang Yu; Guo, Hui Shu; Piao, Hong Mei; Li, Liang chang; Li, Guang Zhao; Lin, Zhen Hua; Yan, Guang Hai

    2012-10-26

    Highlights: Black-Right-Pointing-Pointer Silibinin diminishes ovalbumin-induced inflammatory reactions in the mouse lung. Black-Right-Pointing-Pointer Silibinin reduces the levels of various cytokines into the lung of allergic mice. Black-Right-Pointing-Pointer Silibinin prevents the development of airway hyperresponsiveness in allergic mice. Black-Right-Pointing-Pointer Silibinin suppresses NF-{kappa}B transcriptional activity. -- Abstract: Allergic asthma is a chronic inflammatory disease regulated by coordination of T-helper2 (Th2) type cytokines and inflammatory signal molecules. Silibinin is one of the main flavonoids produced by milk thistle, which is reported to inhibit the inflammatory response by suppressing the nuclear factor-kappa B (NF-{kappa}B) pathway. Because NF-{kappa}B activation plays a pivotal role in the pathogenesis of allergic inflammation, we have investigated the effect of silibinin on a mouse ovalbumin (OVA)-induced asthma model. Airway hyperresponsiveness, cytokines levels, and eosinophilic infiltration were analyzed in bronchoalveolar lavage fluid and lung tissue. Pretreatment of silibinin significantly inhibited airway inflammatory cell recruitment and peribronchiolar inflammation and reduced the production of various cytokines in bronchoalveolar fluid. In addition, silibinin prevented the development of airway hyperresponsiveness and attenuated the OVA challenge-induced NF-{kappa}B activation. These findings indicate that silibinin protects against OVA-induced airway inflammation, at least in part via downregulation of NF-{kappa}B activity. Our data support the utility of silibinin as a potential medicine for the treatment of asthma.

  19. Simulators and difficult airway management skills.

    PubMed

    Schaefer, John J

    2004-01-01

    Although difficult airway management remains one of the leading factors in anaesthetic deaths, there have been tremendous advances in the field in the last few decades. The question is, are advanced airway management skills being taught and used? Of the numerous training tools available, simulators have the advantages of providing whole-task learning with the potential to change behaviour and, when applied to large groups of trainees, the possibility of achieving standardized application of the safest practices for a range of scenarios limited only by the creativity of the program designers. Partial-task trainers include computer-based software programs and simulators. Full-scale simulators include a variety of products from several manufacturers. To take full advantage of simulators as educational tools, curricula should be designed around a set of educational objectives that address the objectives of learning in all three skill domains (cognitive, psychomotor, and affective). Simulation experiences using partial-task or whole-task trainers should be coupled whenever feasible with a structured clinical experience in airway management. This can best be achieved through a dedicated airway management rotation. Monitored procedure logs may also be used. Whether using a simulator or in a clinical rotation, experiences should be graded, for example, gaining experience in an adult population before gaining experience in paediatrics and in each population mastering airway management skills for common scenarios before advancing to more complicated techniques such as fibreoptic bronchoscopy. PMID:14717871

  20. Ozone enhances diesel exhaust particles (DEP)-induced interleukin-8 (IL-8) gene expression in human airway epithelial cells through activation of nuclear factors- kappaB (NF-kappaB) and IL-6 (NF-IL6).

    PubMed

    Kafoury, Ramzi M; Kelley, James

    2005-12-01

    Ozone, a highly reactive oxidant gas is a major component of photochemical smog. As an inhaled toxicant, ozone induces its adverse effects mainly on the lung. Inhalation of particulate matter has been reported to cause airway inflammation in humans and animals. Furthermore, epidemiological evidence has indicated that exposure to particulate matter (PM[2.5-10]), including diesel exhaust particles (DEP) has been correlated with increased acute and chronic respiratory morbidity and exacerbation of asthma. Previously, exposure to ozone or particulate matter and their effect on the lung have been addressed as separate environmental problems. Ozone and particulate matter may be chemically coupled in the ambient air. In the present study we determined whether ozone exposure enhances DEP effect on interleukin-8 (IL-8) gene expression in human airway epithelial cells. We report that ozone exposure (0.5 ppm x 1 hr) significantly increased DEP-induced IL-8 gene expression in A549 cells (117 +/- 19 pg/ml, n = 6, p < 0.05) as compared to cultures treated with DEP (100 microg/ml x 4 hr) alone (31 +/- 3 pg/ml, n = 6), or cultures exposed to purified air (24 +/- 6 pg/ml, n = 6). The increased DEP-induced IL-8 gene expression following ozone exposure was attributed to ozone-induced increase in the activity of the transcription factors NF-kappaB and NF-IL6. The results of the present study indicate that ozone exposure enhances the toxicity of DEP in human airway epithelial cells by augmenting IL-8 gene expression, a potent chemoattractant of neutrophils in the lung. PMID:16819095

  1. c-Jun N-terminal kinase and Akt signalling pathways regulating tumour necrosis factor-α-induced interleukin-32 expression in human lung fibroblasts: implications in airway inflammation

    PubMed Central

    Li, Dagen; Chen, Dapeng; Zhang, Xuemei; Wang, Hong; Song, Zixin; Xu, Wenchun; He, Yujuan; Yin, Yibing; Cao, Ju

    2015-01-01

    Airway inflammatory diseases such as chronic obstructive pulmonary disease (COPD) and asthma are associated with elevated expression of interleukin-32 (IL-32), a recently described cytokine that appears to play a critical role in inflammation. However, so far, the regulation of pulmonary IL-32 production has not been fully established. We examined the expression of IL-32 by tumour necrosis factor-α (TNF-α) in primary human lung fibroblasts. Human lung fibroblasts were cultured in the presence or absence of TNF-α and/or other cytokines/Toll-like receptor (TLR) ligands or various signalling molecule inhibitors to analyse the expression of IL-32 by quantitative RT-PCR and ELISA. Next, activation of Akt and c-Jun N-terminal kinase (JNK) signalling pathways was investigated by Western blot. Interleukin-32 mRNA of four spliced isoforms (α,β,γ and δ) was up-regulated upon TNF-α stimulation, which was associated with a significant IL-32 protein release from TNF-α-activated human lung fibroblasts. The combination of interferon-γ and TNF-α induced enhanced IL-32 release in human lung fibroblasts, whereas IL-4, IL-17A, IL-27 and TLR ligands did not alter IL-32 release in human lung fibroblasts either alone, or in combination with TNF-α. Furthermore, the activation of Akt and JNK pathways regulated TNF-α-induced IL-32 expression in human lung fibroblasts, and inhibition of the Akt and JNK pathways was able to suppress the increased release of IL-32 to nearly the basal level. These data suggest that TNF-α may be involved in airway inflammation via the induction of IL-32 by activating Akt and JNK signalling pathways. Therefore, the TNF-α/IL-32 axis may be a potential therapeutic target for airway inflammatory diseases. PMID:25157456

  2. Intrathoracic airway wall detection using graph search and scanner PSF information

    NASA Astrophysics Data System (ADS)

    Reinhardt, Joseph M.; Park, Wonkyu; Hoffman, Eric A.; Sonka, Milan

    1997-05-01

    Measurements of the in vivo bronchial tree can be used to assess regional airway physiology. High-resolution CT (HRCT) provides detailed images of the lungs and has been used to evaluate bronchial airway geometry. Such measurements have been sued to assess diseases affecting the airways, such as asthma and cystic fibrosis, to measure airway response to external stimuli, and to evaluate the mechanics of airway collapse in sleep apnea. To routinely use CT imaging in a clinical setting to evaluate the in vivo airway tree, there is a need for an objective, automatic technique for identifying the airway tree in the CT images and measuring airway geometry parameters. Manual or semi-automatic segmentation and measurement of the airway tree from a 3D data set may require several man-hours of work, and the manual approaches suffer from inter-observer and intra- observer variabilities. This paper describes a method for automatic airway tree analysis that combines accurate airway wall location estimation with a technique for optimal airway border smoothing. A fuzzy logic, rule-based system is used to identify the branches of the 3D airway tree in thin-slice HRCT images. Raycasting is combined with a model-based parameter estimation technique to identify the approximate inner and outer airway wall borders in 2D cross-sections through the image data set. Finally, a 2D graph search is used to optimize the estimated airway wall locations and obtain accurate airway borders. We demonstrate this technique using CT images of a plexiglass tube phantom.

  3. Examining the factor structure of the recovery assessment scale.

    PubMed

    Corrigan, Patrick W; Salzer, Mark; Ralph, Ruth O; Sangster, Yvette; Keck, Lorraine

    2004-01-01

    This article follows up on earlier research examining the factor structure of a measure of recovery from serious mental illness. Exactly 1,824 persons with serious mental illness who were participating in the baseline interview for a multistate study on consumer-operated services completed the Recovery Assessment Scale (RAS) plus measures representing hope, meaning of life, quality of life, symptoms, and empowerment. Results of exploratory and subsequent confirmatory factor analyses of the RAS for random halves of the sample yielded five factors: personal confidence and hope, willingness to ask for help, goal and success orientation, reliance on others, and no domination by symptoms. Subsequent regression analyses showed that these five factors were uniquely related to the additional constructs assessed in the study. We compared these findings with those of other studies to summarize the factor structure that currently emerges on recovery. PMID:15957202

  4. Airway responsiveness to psychological processes in asthma and health

    PubMed Central

    Ritz, Thomas

    2012-01-01

    Psychosocial factors have been found to impact airway pathophysiology in respiratory disease with considerable consistency. Influences on airway mechanics have been studied particularly well. The goal of this article is to review the literature on airway responses to psychological stimulation, discuss potential pathways of influence, and present a well-established emotion-induction paradigm to study airway obstruction elicited by unpleasant stimuli. Observational studies have found systematic associations between lung function and daily mood changes. The laboratory-based paradigm of bronchoconstrictive suggestion has been used successfully to elicit airway obstruction in a substantial proportion of asthmatic individuals. Other studies have demonstrated modulation of airway responses to standard airway challenges with exercise, allergens, or pharmacological agents by psychological factors. Standardized emotion-induction techniques have consistently shown airway constriction during unpleasant stimulation, with surgery, blood, and injury stimuli being particularly powerful. Findings with various forms of stress induction have been more mixed. A number of methodological factors may account for variability across studies, such as choice of measurement technique, temporal association between stimulation and measurement, and the specific quality and intensity of the stimulus material, in particular the extent of implied action-orientation. Research has also begun to elucidate physiological processes associated with psychologically induced airway responses, with vagal excitation and ventilatory influences being the most likely candidate pathways, whereas the role of specific central nervous system pathways and inflammatory processes has been less studied. The technique of emotion-induction using films has the potential to become a standardized challenge paradigm for the further exploration of airway hyperresponsiveness mediated by central nervous system processes. PMID

  5. Supraglottic airway devices.

    PubMed

    Ramachandran, Satya Krishna; Kumar, Anjana M

    2014-06-01

    Supraglottic airway devices (SADs) are used to keep the upper airway open to provide unobstructed ventilation. Early (first-generation) SADs rapidly replaced endotracheal intubation and face masks in > 40% of general anesthesia cases due to their versatility and ease of use. Second-generation devices have further improved efficacy and utility by incorporating design changes. Individual second-generation SADs have allowed more dependable positive-pressure ventilation, are made of disposable materials, have integrated bite blocks, are better able to act as conduits for tracheal tube placement, and have reduced risk of pulmonary aspiration of gastric contents. SADs now provide successful rescue ventilation in > 90% of patients in whom mask ventilation or tracheal intubation is found to be impossible. However, some concerns with these devices remain, including failing to adequately ventilate, causing airway damage, and increasing the likelihood of pulmonary aspiration of gastric contents. Careful patient selection and excellent technical skills are necessary for successful use of these devices. PMID:24891199

  6. Glucagon Like Peptide-1 (GLP-1) Modulates OVA-Induced Airway Inflammation and Mucus Secretion Involving a Protein Kinase A (PKA)-Dependent Nuclear Factor-κB (NF-κB) Signaling Pathway in Mice

    PubMed Central

    Zhu, Tao; Wu, Xiao-ling; Zhang, Wei; Xiao, Min

    2015-01-01

    Asthma is a common chronic pulmonary inflammatory disease, featured with mucus hyper-secretion in the airway. Recent studies found that glucagon like peptide-1 (GLP-1) analogs, including liraglutide and exenatide, possessed a potent anti-inflammatory property through a protein kinase A (PKA)-dependent signaling pathway. Therefore, the aim of current study was to investigate the value of GLP-1 analog therapy liraglutide in airway inflammation and mucus secretion in a murine model of ovalbumin (OVA)-induced asthma, and its underlying molecular mechanism. In our study, BALB/c mice were sensitized and challenged by OVA to induce chronic asthma. Pathological alterations, the number of cells and the content of inflammatory mediators in bronchoalveolar lavage fluid (BALF), and mucus secretion were observed and measured. In addition, the mRNA and protein expression of E-selectin and MUC5AC were analyzed by qPCR and Western blotting. Then, the phosphorylation of PKA and nuclear factor-κB (NF-κB) p65 were also measured by Western blotting. Further, NF-κB p65 DNA binding activity was detected by ELISA. OVA-induced airway inflammation, airway mucus hyper-secretion, the up-regulation of E-selectin and MUC5AC were remarkably inhibited by GLP-1 in mice (all p < 0.01). Then, we also found that OVA-reduced phosphorylation of PKA, and OVA-enhanced NF-κB p65 activation and NF-κB p65 DNA binding activity were markedly improved by GLP-1 (all p < 0.01). Furthermore, our data also figured out that these effects of GLP-1 were largely abrogated by the PKA inhibitor H-89 (all p < 0.01). Taken together, our results suggest that OVA-induced asthma were potently ameliorated by GLP-1 possibly through a PKA-dependent inactivation of NF-κB in mice, indicating that GLP-1 analogs may be considered an effective and safe drug for the potential treatment of asthma in the future. PMID:26343632

  7. Persistent severe hypereosinophilic asthma is not associated with airway remodeling.

    PubMed

    Alagha, Khuder; Jarjour, Baihas; Bommart, Sebastien; Aviles, Berta; Varrin, Muriel; Gamez, Anne Sophie; Molinari, Nicolas; Vachier, Isabelle; Paganin, Fabrice; Chanez, Pascal; Bourdin, Arnaud

    2015-02-01

    Hypereosinophilic asthma (HEA) is considered as a specific severe asthma phenotype. Whether eosinophils have a link with airway remodeling characterized by pathological (thickening of the basement membrane), functional (persistent airflow impairment and decline in lung function) and imaging features (increase airway wall thickness at CT scan) is still debated. In a one year prospective cohort of 142 severe asthma patients (according to IMI), 14 persistent HEA patients (defined by a persistent blood eosinophilia >500/mm(3) at two consecutive visits) were identified and compared with ten patients without any blood eosinophilia during the follow-up period (NEA, blood eosinophilia always <500/mm(3)). Airflow and lung volumes were recorded. Bronchial biopsies obtained at enrollment were stained for eosinophils (EG2) and basement membrane thickness (BM) was quantified. Imaging by CT scan acquisition was standardized and bronchial abnormalities quantified. ACQ score and exacerbations were prospectively recorded. HEA was not associated with preeminent features of airway remodeling assessed by airflow impairment (Best ever FEV1 values 97% ± 20 in HEA vs. 80 ± 24% in NEA, p = 0.020), decline of FEV1 (FEV1 Decline 40 ± 235 ml/y in HEA vs. 19 ± 40 ml/y in NEA, P = 0.319), submucosal abnormalities (BM thickness 7.80 ± 2.66 μm in HEA vs. 6.84 ± 2.59 in NEA, p = 0.37) and airway wall thickening at CT-scan (0.250 ± 0.036 mm vs. 0.261 ± 0.043, p = 0.92). Eosinophils blood count was inversely correlated with semiquantitative imaging score (rho -0.373, p = 0.039). Smoking history and positive skin prick tests were independent risk factors for increased BM thickening. Outcomes were similar in both populations (Control and exacerbations). Persistent HEA is not associated with evidences of airway remodeling. PMID:25592243

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

    PubMed

    Kaminsky, David A

    2012-01-01

    Spirometry is considered the primary method to detect the air flow limitation associated with obstructive lung disease. However, air flow limitation is the end-result of many factors that contribute to obstructive lung disease. One of these factors is increased airway resistance. Airway resistance is traditionally measured by relating air flow and driving pressure using body plethysmography, thus deriving airway resistance (R(aw)), specific airway resistance (sR(aw)), and specific airway conductance (sG(aw)). Other methods to measure airway resistance include the forced oscillation technique (FOT), which allows calculation of respiratory system resistance (R(RS)) and reactance (X(RS)), and the interrupter technique, which allows calculation of interrupter resistance (R(int)). An advantage of these other methods is that they may be easier to perform than spirometry, making them particularly suited to patients who cannot perform spirometry, such as young children, patients with neuromuscular disorders, or patients on mechanical ventilation. Since spirometry also requires a deep inhalation, which can alter airway resistance, these alternative methods may provide more sensitive measures of airway resistance. Furthermore, the FOT provides unique information about lung mechanics that is not available from analysis using spirometry, body plethysmography, or the interrupter technique. However, it is unclear whether any of these measures of airway resistance contribute clinically important information to the traditional measures derived from spirometry (FEV(1), FVC, and FEV(1)/FVC). The purpose of this paper is to review the physiology and methodology of these measures of airway resistance, and then focus on their clinical utility in relation to each other and to spirometry. PMID:22222128

  9. Upper and lower pharyngeal airway space in West-Tamil Nadu population

    PubMed Central

    Mani, Prabhakaran; Muthukumar, Karthi; Krishnan, Prabhakar; Senthil Kumar, K. P.

    2015-01-01

    Aim: To compare the upper and lower pharyngeal airway (LPA) width in Class II malocclusion patients with low, average, and high vertical growth patterns. Study Design: Cross-sectional analytical study. Materials and Methods: Pretreatment lateral cephalometric films of 90 Class II subjects were used to measure the upper and LPAs. The inclusion criteria were subjects of West-Tamil Nadu, aged between 14 and 25 years, only skeletal Class II subjects of either gender and no pharyngeal pathology at initial visit. The sample comprised a total of 90 Class II subjects divided into three groups according to the vertical facial pattern: Normodivergent (n = 30), hypodivergent (n = 30), and hyperdivergent (n = 30). The assessment of upper and LPAs was done according to McNamara's airway analysis. Statistical Analysis: The intergroup comparison of the upper and LPAs was performed with one-way analysis of variance and the Tukey test was used to compare among the various vertical patterns. Results: Skeletal Class II subjects with hyperdivergent facial pattern showed statistically significant narrow upper pharyngeal width when compared to normodivergent and hypodivergent facial patterns. No statistically significant difference was found in the lower pharyngeal width in all three vertical facial growth patterns. Conclusion: Subjects with Class II malocclusions and hyperdivergent growth pattern have significantly narrow upper pharyngeal airway space when compared to other two vertical patterns. Narrow pharyngeal airway space is one of the predisposing factors for mouth breathing and obstructive sleep apnea. PMID:26538913

  10. Issues of critical airway management (Which anesthesia; which surgical airway?).

    PubMed

    Bonanno, Fabrizio Giuseppe

    2012-10-01

    Which anesthesia for patients with critical airway? Safe and effective analgesia and anesthesia in critical airway is a skilled task especially after severe maxillofacial injury combined with head injury and hemorrhagic shock. If on one side sedation is wanted, on the other hand it may worsen the airway and hemodynamic situation to a point where hypoventilation and decrease of blood pressure, common side-effect of many opioids, may prejudice the patient's level of consciousness and hemodynamic compensation, compounding an already critical situation. What to do when endotracheal intubation fails and blood is trickling down the airways in an unconscious patient or when a conscious patient has to sit up to breathe? Which surgical airway in critical airway? Comparative studies among the various methods of emergency surgical airway would be unethical; furthermore, operator's training and experience is relevant for indications and performance. PMID:23248494

  11. INHIBITION OF PAN NEUROTROPHIN RECEPTOR P75 ATTENUATES DIESEL PARTICULATE-INDUCED ENHANCEMENT OF ALLERGIC AIRWAY RESPONSES IN C57/BL6J MICE

    EPA Science Inventory

    Recent investigations have linked neurotrophins including nerve growth factor (NGF), neurotrophin-3 (NT-3), and brain-derived neurotrophic factor (BDNF) to allergic airways diseases. Antibody blockade of NGF attenuates airway resistance in allergic mice. Diesel exhaust particle...

  12. Total airway reconstruction.

    PubMed

    Connor, Matthew P; Barrera, Jose E; Eller, Robert; McCusker, Scott; O'Connor, Peter

    2013-02-01

    We present a case of obstructive sleep apnea (OSA) that required multilevel surgical correction of the airway and literature review and discuss the role supraglottic laryngeal collapse can have in OSA. A 34-year-old man presented to a tertiary otolaryngology clinic for treatment of OSA. He previously had nasal and palate surgeries and a Repose tongue suspension. His residual apnea hypopnea index (AHI) was 67. He had a dysphonia associated with a true vocal cord paralysis following resection of a benign neck mass in childhood. He also complained of inspiratory stridor with exercise and intolerance to continuous positive airway pressure. Physical examination revealed craniofacial hypoplasia, full base of tongue, and residual nasal airway obstruction. On laryngoscopy, the paretic aryepiglottic fold arytenoid complex prolapsed into the laryngeal inlet with each breath. This was more pronounced with greater respiratory effort. Surgical correction required a series of operations including awake tracheostomy, supraglottoplasty, midline glossectomy, genial tubercle advancement, maxillomandibular advancement, and reconstructive rhinoplasty. His final AHI was 1.9. Our patient's supraglottic laryngeal collapse constituted an area of obstruction not typically evaluated in OSA surgery. In conjunction with treating nasal, palatal, and hypopharyngeal subsites, our patient's supraglottoplasty represented a key component of his success. This case illustrates the need to evaluate the entire upper airway in a complicated case of OSA. PMID:22965285

  13. Epithelial hyperplasia, airways

    Cancer.gov

    Number of respiratory epithelial cells is increased diffusely or focally. Frequently luminal protrusions are observed, sometimes forming papillae. Mucous (goblet) cell metaplastic hyperplasia is a variant, in which the respiratory epithelium of conducting airways is replaced by mucous cells either as a single or a pseudostratified layer.

  14. Advances in prehospital airway management

    PubMed Central

    Jacobs, PE; Grabinsky, A

    2014-01-01

    Prehospital airway management is a key component of emergency responders and remains an important task of Emergency Medical Service (EMS) systems worldwide. The most advanced airway management techniques involving placement of oropharyngeal airways such as the Laryngeal Mask Airway or endotracheal tube. Endotracheal tube placement success is a common measure of out-of-hospital airway management quality. Regional variation in regard to training, education, and procedural exposure may be the major contributor to the findings in success and patient outcome. In studies demonstrating poor outcomes related to prehospital-attempted endotracheal intubation (ETI), both training and skill level of the provider are usually often low. Research supports a relationship between the number of intubation experiences and ETI success. National standards for certification of emergency medicine provider are in general too low to guarantee good success rate in emergency airway management by paramedics and physicians. Some paramedic training programs require more intense airway training above the national standard and some EMS systems in Europe staff their system with anesthesia providers instead. ETI remains the cornerstone of definitive prehospital airway management, However, ETI is not without risk and outcomes data remains controversial. Many systems may benefit from more input and guidance by the anesthesia department, which have higher volumes of airway management procedures and extensive training and experience not just with training of airway management but also with different airway management techniques and adjuncts. PMID:24741499

  15. Supraglottic airway devices in children

    PubMed Central

    Ramesh, S; Jayanthi, R

    2011-01-01

    Modern anaesthesia practice in children was made possible by the invention of the endotracheal tube (ET), which made lengthy and complex surgical procedures feasible without the disastrous complications of airway obstruction, aspiration of gastric contents or asphyxia. For decades, endotracheal intubation or bag-and-mask ventilation were the mainstays of airway management. In 1983, this changed with the invention of the laryngeal mask airway (LMA), the first supraglottic airway device that blended features of the facemask with those of the ET, providing ease of placement and hands-free maintenance along with a relatively secure airway. The invention and development of the LMA by Dr. Archie Brain has had a significant impact on the practice of anaesthesia, management of the difficult airway and cardiopulmonary resuscitation in children and neonates. This review article will be a brief about the clinical applications of supraglottic airways in children. PMID:22174464

  16. Factor-Analytic Procedures for Assessing Response Pattern Scalability

    ERIC Educational Resources Information Center

    Ferrando, Pere J.

    2007-01-01

    This paper proposes procedures for assessing the fit of a psychometric model at the level of the individual respondent. The procedures are intended for personality measures made up of Likert-type items, which, in applied research, are usually analyzed by means of factor analysis. Two scalability indices are proposed, which can be considered as…

  17. Mechanical ventilation causes airway distension with proinflammatory sequelae in mice.

    PubMed

    Nickles, Hannah T; Sumkauskaite, Migle; Wang, Xin; Wegner, Ingmar; Puderbach, Michael; Kuebler, Wolfgang M

    2014-07-01

    The pathogenesis of ventilator-induced lung injury has predominantly been attributed to overdistension or mechanical opening and collapse of alveoli, whereas mechanical strain on the airways is rarely taken into consideration. Here, we hypothesized that mechanical ventilation may cause significant airway distension, which may contribute to the pathological features of ventilator-induced lung injury. C57BL/6J mice were anesthetized and mechanically ventilated at tidal volumes of 6, 10, or 15 ml/kg body wt. Mice were imaged by flat-panel volume computer tomography, and central airways were segmented and rendered in 3D for quantitative assessment of airway distension. Alveolar distension was imaged by intravital microscopy. Functional dead space was analyzed in vivo, and proinflammatory cytokine release was analyzed in isolated, ventilated tracheae. CT scans revealed a reversible, up to 2.5-fold increase in upper airway volume during mechanical ventilation compared with spontaneous breathing. Airway distension was most pronounced in main bronchi, which showed the largest volumes at tidal volumes of 10 ml/kg body wt. Conversely, airway distension in segmental bronchi and functional dead space increased almost linearly, and alveolar distension increased even disproportionately with higher tidal volumes. In isolated tracheae, mechanical ventilation stimulated the release of the early-response cytokines TNF-α and IL-1β. Mechanical ventilation causes a rapid, pronounced, and reversible distension of upper airways in mice that is associated with an increase in functional dead space. Upper airway distension is most pronounced at moderate tidal volumes, whereas higher tidal volumes redistribute preferentially to the alveolar compartment. Airway distension triggers proinflammatory responses and may thus contribute relevantly to ventilator-induced pathologies. PMID:24816486

  18. [COMPLEX ASSESSMENT OF ENVIRONMENTAL FACTORS AND POSTVACCINAL IMMUNE STATE].

    PubMed

    Kryazhev, D A; Boev, M V; Tulina, L M; Neplokhov, A A; Boev, V M

    2016-01-01

    This article was written on the base of the analysis of data of protocols of annual serological sturdies of the post-vaccination immunity status in indicator groups of populations, the analysis of samples of drinking water air and soil with the assessment of the socio-economic development of mono-towns and rural settlements. In the article there is reflected the comprehensive assessment of environmental factors and specific features of the formation of socio-economic conditions of rural communities and mono towns. There was performed a comparative assessment of the status of post-vaccination immunity to infections controlled by specific means of prevention, in different age groups in mono towns and rural settlements. There was established a dependence of the formation of post-vaccination immunity on the state of environmental factors. PMID:27266020

  19. Management of the Traumatized Airway.

    PubMed

    Jain, Uday; McCunn, Maureen; Smith, Charles E; Pittet, Jean-Francois

    2016-01-01

    There is a lack of evidence-based approach regarding the best practice for airway management in patients with a traumatized airway. General recommendations for the management of the traumatized airway are summarized in table 5. Airway trauma may not be readily apparent, and its evaluation requires a high level of suspicion for airway disruption and compression. For patients with facial trauma, control of the airway may be significantly impacted by edema, bleeding, inability to clear secretions, loss of bony support, and difficulty with face mask ventilation. With the airway compression from neck swelling or hematoma, intubation attempts can further compromise the airway due to expanding hematoma. For patients with airway disruption, the goal is to pass the tube across the injured area without disrupting it or to insert the airway distal to the injury using a surgical approach. If airway injury is extensive, a surgical airway distal to the site of injury may be the best initial approach. Alternatively, if orotracheal intubation is chosen, spontaneous ventilation may be maintained or RSI may be performed. RSI is a common approach. Thus, some of the patients intubated may subsequently require tracheostomy. A stable patient with limited injuries may not require intubation but should be watched carefully for at least several hours. Because of a paucity of evidence-based data, the choice between these approaches and the techniques utilized is a clinical decision depending on the patient's condition, clinical setting, injuries to airway and other organs, and available personnel, expertise, and equipment. Inability to obtain a definitive airway is always an absolute indication for an emergency cricothyroidotomy or surgical tracheostomy. PMID:26517857

  20. Assessing the five-factor model of personality description.

    PubMed

    Briggs, S R

    1992-06-01

    Several approaches to assessing the dimensions of the five-factor model are reviewed and evaluated. The items in the assessment instrument may be adjectives or phrases, and the instrument itself may have been developed specifically to measure the five factors or may have been reinterpreted in terms of the five-factor model. Data are presented comparing an adjective-based measure of the model (Goldberg, 1990) with two phrase-based measures (Costa & McCrae, 1985; Hogan, 1986), and recommendations are made for the choice of an instrument in different research contexts. Allport's (1937) distinctions between the structure of the trait lexicon and the structure of personality in individuals are reiterated. PMID:1635044

  1. Snoring-Induced Nerve Lesions in the Upper Airway

    PubMed Central

    Poothrikovil, Rajesh P; Al Abri, Mohammed A

    2012-01-01

    The prevalence of habitual snoring is extremely high in the general population, and is reported to be roughly 40% in men and 20% in women. The low-frequency vibrations of snoring may cause physical trauma and, more specifically, peripheral nerve injuries, just as jobs which require workers to use vibrating tools over the course of many years result in local nerve lesions in the hands. Histopathological analysis of upper airway (UA) muscles have shown strong evidence of a varying severity of neurological lesions in groups of snoring patients. Neurophysiological assessment shows evidence of active and chronic denervation and re-innervation in the palatopharyngeal muscles of obstructive sleep apnoea (OSA) patients. Neurogenic lesions of UA muscles induced by vibration trauma impair the reflex dilation abilities of the UA, leading to an increase in the possibility of UA collapse. The neurological factors which are partly responsible for the progressive nature of OSAS warrant the necessity of early assessment in habitual snorers. PMID:22548134

  2. Intratracheal Bleomycin Causes Airway Remodeling and Airflow Obstruction in Mice

    PubMed Central

    Polosukhin, Vasiliy V.; Degryse, Amber L.; Newcomb, Dawn C.; Jones, Brittany R.; Ware, Lorraine B.; Lee, Jae Woo; Loyd, James E.; Blackwell, Timothy S.; Lawson, William E.

    2014-01-01

    Introduction In addition to parenchymal fibrosis, fibrotic remodeling of the distal airways has been reported in interstitial lung diseases. Mechanisms of airway wall remodeling, which occurs in a variety of chronic lung diseases, are not well defined and current animal models are limited. Methods We quantified airway remodeling in lung sections from subjects with idiopathic pulmonary fibrosis (IPF) and controls. To investigate intratracheal bleomycin as a potential animal model for fibrotic airway remodeling, we evaluated lungs from C57BL/6 mice after bleomycin treatment by histologic scoring for fibrosis and peribronchial inflammation, morphometric evaluation of subepithelial connective tissue volume density, TUNEL assay, and immunohistochemistry for transforming growth factor β1 (TGFβ1), TGFβ2, and the fibroblast marker S100A4. Lung mechanics were determined at 3 weeks post-bleomycin. Results IPF lungs had small airway remodeling with increased bronchial wall thickness compared to controls. Similarly, bleomycin treated mice developed dose-dependent airway wall inflammation and fibrosis and greater airflow resistance after high dose bleomycin. Increased TUNEL+ bronchial epithelial cells and peribronchial inflammation were noted by 1 week, and expression of TGFβ1 and TGFβ2 and accumulation of S100A4+ fibroblasts correlated with airway remodeling in a bleomycin dose-dependent fashion. Conclusions IPF is characterized by small airway remodeling in addition to parenchymal fibrosis, a pattern also seen with intratracheal bleomycin. Bronchial remodeling from intratracheal bleomycin follows a cascade of events including epithelial cell injury, airway inflammation, pro-fibrotic cytokine expression, fibroblast accumulation, and peribronchial fibrosis. Thus, this model can be utilized to investigate mechanisms of airway remodeling. PMID:22394287

  3. Coordinate Control of Expression of Nrf2-Modulated Genes in the Human Small Airway Epithelium Is Highly Responsive to Cigarette Smoking

    PubMed Central

    Hübner, Ralf-Harto; Schwartz, Jamie D; De Bishnu, P; Ferris, Barbara; Omberg, Larsson; Mezey, Jason G; Hackett, Neil R; Crystal, Ronald G

    2009-01-01

    Nuclear factor erythroid 2–related factor 2 (Nrf2) is an oxidant-responsive transcription factor known to induce detoxifying and antioxidant genes. Cigarette smoke, with its large oxidant content, is a major stress on the cells of small airway epithelium, which are vulnerable to oxidant damage. We assessed the role of cigarette smoke in activation of Nrf2 in the human small airway epithelium in vivo. Fiberoptic bronchoscopy was used to sample the small airway epithelium in healthy-nonsmoker and healthy-smoker, and gene expression was assessed using microarrays. Relative to nonsmokers, Nrf2 protein in the small airway epithelium of smokers was activated and localized in the nucleus. The human homologs of 201 known murine Nrf2-modulated genes were identified, and 13 highly smoking-responsive Nrf2-modulated genes were identified. Construction of an Nrf2 index to assess the expression levels of these 13 genes in the airway epithelium of smokers showed coordinate control, an observation confirmed by quantitative PCR. This coordinate level of expression of the 13 Nrf2-modulated genes was independent of smoking history or demographic parameters. The Nrf2 index was used to identify two novel Nrf2-modulated, smoking-responsive genes, pirin (PIR) and UDP glucuronosyltransferase 1-family polypeptide A4 (UGT1A4). Both genes were demonstrated to contain functional antioxidant response elements in the promoter region. These observations suggest that Nrf2 plays an important role in regulating cellular defenses against smoking in the highly vulnerable small airway epithelium cells, and that there is variability within the human population in the Nrf2 responsiveness to oxidant burden. PMID:19593404

  4. Systems physiology of the airways in health and obstructive pulmonary disease.

    PubMed

    Bates, Jason H T

    2016-09-01

    Fresh air entering the mouth and nose is brought to the blood-gas barrier in the lungs by a repetitively branching network of airways. Provided the individual airway branches remain patent, this airway tree achieves an enormous amplification in cross-sectional area from the trachea to the terminal bronchioles. Obstructive lung diseases such as asthma occur when airway patency becomes compromised. Understanding the pathophysiology of these obstructive diseases thus begins with a consideration of the factors that determine the caliber of an individual airway, which include the force balance between the inward elastic recoil of the airway wall, the outward tethering forces of its parenchymal attachments, and any additional forces due to contraction of airway smooth muscle. Other factors may also contribute significantly to airway narrowing, such as thickening of the airway wall and accumulation of secretions in the lumen. Airway obstruction becomes particularly severe when these various factors occur in concert. However, the effect of airway abnormalities on lung function cannot be fully understood only in terms of what happens to a single airway because narrowing throughout the airway tree is invariably heterogeneous and interdependent. Obstructive lung pathologies thus manifest as emergent phenomena arising from the way in which the airway tree behaves a system. These emergent phenomena are studied with clinical measurements of lung function made by spirometry and by mechanical impedance measured with the forced oscillation technique. Anatomically based computational models are linking these measurements to underlying anatomic structure in systems physiology terms. WIREs Syst Biol Med 2016, 8:423-437. doi: 10.1002/wsbm.1347 For further resources related to this article, please visit the WIREs website. PMID:27340818

  5. Upper and lower airway pathology in young children with allergic- and non-allergic rhinitis.

    PubMed

    Chawes, Bo L K

    2011-05-01

    of the nasal mucosa in children already at age 6 years. Non-allergic rhinitis exhibited no change in the nasal airway patency, but some nasal eosinophilia albeit less than children with allergic rhinitis. These findings suggest different pathology in allergic- and non-allergic rhinitis which may have important clinical implications for early pharmacological treatment of rhinitis in young children. In paper II, we utilized the nasal airway patency end-points derived from paper I to examine whether upper and lower airway patency are associated. Upper airway patency was assessed by acoustic rhinometry before and after intranasal α-agonist and lower airway patency by spirometry before and after inhaled β2-agonist. Upper and lower airway patencies were strongly associated and independent of body size, rhinitis and asthma. The association was consistent for both baseline values and for decongested nasal airway patency and post-β2 FEV1. Blood and nasal eosinophilia were also associated with nasal airway obstruction. This suggests generalized diminished airway dimensions as a novel susceptibility factor for concurrent symptoms of asthma and rhinitis in early childhood and supports the notion of a common pathophysiology in asthma and rhinitis. The clinical interpretation of these findings is that all children presenting either rhinitis or asthma should be considered inflamed in the entire respiratory tract. In paper III, we aimed to describe asthma and intermediary asthma end-points associated with allergic- and non-allergic rhinitis in preschool-aged children. At age 7 years, we evaluated prevalence of asthma, eczema, food sensitization, and filaggrin mutations; levels of total IgE, FeNO, and blood-eosinophils; lung function and bronchial responsiveness to cold dry air. We found that asthma was similarly associated with allergic- and non-allergic rhinitis suggesting a link between upper and lower airway diseases beyond an allergy associated inflammation. Only children

  6. Assessment of maladaptive variants of Five-Factor Model traits.

    PubMed

    Lynam, Donald R

    2012-12-01

    Research has shown that the personality disorders (PDs) bear consistent relations to general models of personality functioning, particularly in relation to the Five-Factor Model (FFM). In addition to suggesting that the PDs might be understood as constellations of traits from the FFM, this research also suggests that these constellations might be used to assess the PDs. The present article reviews previous research using the NEO Personality Inventory-Revised (NEO PI-R; Costa & McCrae, ) to assess disordered personality and discusses some shortcomings of this approach. Next, I detail studies that have used what is known about the relations between the FFM and disordered personality to construct new assessments that are grounded in the basic science of personality but designed to assess the more pathological aspects. Finally, the advantages of this approach are outlined. PMID:22321444

  7. Classification of pulmonary airway disease based on mucosal color analysis

    NASA Astrophysics Data System (ADS)

    Suter, Melissa; Reinhardt, Joseph M.; Riker, David; Ferguson, John Scott; McLennan, Geoffrey

    2005-04-01

    Airway mucosal color changes occur in response to the development of bronchial diseases including lung cancer, cystic fibrosis, chronic bronchitis, emphysema and asthma. These associated changes are often visualized using standard macro-optical bronchoscopy techniques. A limitation to this form of assessment is that the subtle changes that indicate early stages in disease development may often be missed as a result of this highly subjective assessment, especially in inexperienced bronchoscopists. Tri-chromatic CCD chip bronchoscopes allow for digital color analysis of the pulmonary airway mucosa. This form of analysis may facilitate a greater understanding of airway disease response. A 2-step image classification approach is employed: the first step is to distinguish between healthy and diseased bronchoscope images and the second is to classify the detected abnormal images into 1 of 4 possible disease categories. A database of airway mucosal color constructed from healthy human volunteers is used as a standard against which statistical comparisons are made from mucosa with known apparent airway abnormalities. This approach demonstrates great promise as an effective detection and diagnosis tool to highlight potentially abnormal airway mucosa identifying a region possibly suited to further analysis via airway forceps biopsy, or newly developed micro-optical biopsy strategies. Following the identification of abnormal airway images a neural network is used to distinguish between the different disease classes. We have shown that classification of potentially diseased airway mucosa is possible through comparative color analysis of digital bronchoscope images. The combination of the two strategies appears to increase the classification accuracy in addition to greatly decreasing the computational time.

  8. Reproducibility of airway wall thickness measurements

    NASA Astrophysics Data System (ADS)

    Schmidt, Michael; Kuhnigk, Jan-Martin; Krass, Stefan; Owsijewitsch, Michael; de Hoop, Bartjan; Peitgen, Heinz-Otto

    2010-03-01

    Airway remodeling and accompanying changes in wall thickness are known to be a major symptom of chronic obstructive pulmonary disease (COPD), associated with reduced lung function in diseased individuals. Further investigation of this disease as well as monitoring of disease progression and treatment effect demand for accurate and reproducible assessment of airway wall thickness in CT datasets. With wall thicknesses in the sub-millimeter range, this task remains challenging even with today's high resolution CT datasets. To provide accurate measurements, taking partial volume effects into account is mandatory. The Full-Width-at-Half-Maximum (FWHM) method has been shown to be inappropriate for small airways1,2 and several improved algorithms for objective quantification of airway wall thickness have been proposed.1-8 In this paper, we describe an algorithm based on a closed form solution proposed by Weinheimer et al.7 We locally estimate the lung density parameter required for the closed form solution to account for possible variations of parenchyma density between different lung regions, inspiration states and contrast agent concentrations. The general accuracy of the algorithm is evaluated using basic tubular software and hardware phantoms. Furthermore, we present results on the reproducibility of the algorithm with respect to clinical CT scans, varying reconstruction kernels, and repeated acquisitions, which is crucial for longitudinal observations.

  9. Airway epithelial cell responses to ozone injury

    SciTech Connect

    Leikauf, G.D.; Simpson, L.G.; Zhao, Qiyu

    1995-03-01

    The airway epithelial cell is an important target in ozone injury. Once activated, the airway epithelium responds in three phases. The initial, or immediate phase, involves activation of constitutive cells, often through direct covalent interactions including the formation of secondary ozonolysis products-hydroxyhydroperoxides, aldehydes, and hydrogen peroxide. Recently, we found hydroxyhydroperoxides to be potent agonists; of bioactive eicosanoid formation by human airway epithelial cells in culture. Other probable immediate events include activation and inactivation of enzymes present on the epithelial surface (e.g., neutral endopeptidase). During the next 2 to 24 hr, or early phase, epithelial cells respond by synthesis and release of chemotactic factors, including chemokines-macrophage inflammatory protein-2, RANTES, and interleukin-8. Infiltrating leukocytes during this period also release elastase, an important agonist of epithelial cell mucus secretion and additional chemokine formation. The third (late) phase of ozone injury is characterized by eosinophil or monocyte infiltration. Cytokine expression leads to alteration of structural protein synthesis, with increases in fibronectin evident by in situ hybridization. Synthesis of epithelial antiproteases, e.g., secretary leukocyte protease inhibitor, may also increase locally 24 to 48 hr after elastase concentrations become excessive. Thus, the epithelium is not merely a passive barrier to ozone injury but has a dynamic role in directing the migration, activating, and then counteracting inflammatory cells. Through these complex interactions, epithelial cells can be viewed as the initiators (alpha) and the receptors (omega) of ozone-induced airway disease. 51 refs., 2 figs., 3 tabs.

  10. Link between vitamin D and airway remodeling

    PubMed Central

    Berraies, Anissa; Hamzaoui, Kamel; Hamzaoui, Agnes

    2014-01-01

    In the last decade, many epidemiologic studies have investigated the link between vitamin D deficiency and asthma. Most studies have shown that vitamin D deficiency increases the risk of asthma and allergies. Low levels of vitamin D have been associated with asthma severity and loss of control, together with recurrent exacerbations. Remodeling is an early event in asthma described as a consequence of production of mediators and growth factors by inflammatory and resident bronchial cells. Consequently, lung function is altered, with a decrease in forced expiratory volume in one second and exacerbated airway hyperresponsiveness. Subepithelial fibrosis and airway smooth muscle cell hypertrophy are typical features of structural changes in the airways. In animal models, vitamin D deficiency enhances inflammation and bronchial anomalies. In severe asthma of childhood, major remodeling is observed in patients with low vitamin D levels. Conversely, the antifibrotic and antiproliferative effects of vitamin D in smooth muscle cells have been described in several experiments. In this review, we briefly summarize the current knowledge regarding the relationship between vitamin D and asthma, and focus on its effect on airway remodeling and its potential therapeutic impact for asthma. PMID:24729717

  11. Upper Airway Mechanics

    PubMed Central

    Verbraecken, Johan A.; De Backer, Wilfried A.

    2009-01-01

    This review discusses the pathophysiological aspects of sleep-disordered breathing, with focus on upper airway mechanics in obstructive and central sleep apnoea, Cheyne-Stokes respiration and obesity hypoventilation syndrome. These disorders constitute the end points of a spectrum with distinct yet interrelated mechanisms that lead to substantial pathology, i.e. increased upper airway collapsibility, control of breathing instability, increased work of breathing, disturbed ventilatory system mechanics and neurohormonal changes. Concepts are changing. Although sleep apnoea is considered more and more to be an increased loop gain disorder, the central type of apnoea is now considered as an obstructive event, because it causes pharyngeal narrowing, associated with prolonged expiration. Although a unifying concept for the pathogenesis is lacking, it seems that these patients are in a vicious circle. Knowledge of common patterns of sleep-disordered breathing may help to identify these patients and guide therapy. PMID:19478479

  12. Assessing the factor structure of a role functioning item bank

    PubMed Central

    Ware, John E.; Bjorner, Jakob B.

    2013-01-01

    Purpose Role functioning (RF) is an important part of health-related quality of life, but is hard to measure due to the wide definition of roles and fluctuations in role participation. This study aims to explore the dimensionality of a newly developed item bank assessing the impact of health on RF. Methods A battery of measures with skip patterns including the new RF bank was completed by 2,500 participants answering only questions on social roles relevant to them. Confirmatory factor analyses were conducted for the participants answering items from all conceptual domains (N = 1193). Conceptually based dimensionality and method effects reflecting positively and negatively worded items were explored in a series of models. Results A bi-factor model (CFI = .93, RMSEA = .08) with one general and four conceptual factors (social, family, occupation, generic) was retained. Positively worded items were excluded from the final solution due to misfit. While a single factor model with methods factors had a poor fit (CFI = .88, RMSEA = .13), high loadings on the general factor in the bi-factor model suggest that the RF bank is sufficiently unidimensional for IRT analysis. Conclusions The bank demonstrated sufficient unidimensionality for IRT-based calibration of all the items on a common metric and development of a computerized adaptive test. PMID:21153710

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

    PubMed

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

    2015-11-01

    We have previously demonstrated increased airway smooth muscle (ASM) mass and airway hyperresponsiveness in whole-life vitamin D-deficient female mice. In this study, we aimed to uncover the molecular mechanisms contributing to altered lung structure and function. RNA was extracted from lung tissue of whole-life vitamin D-deficient and -replete female mice, and gene expression patterns were profiled by RNA sequencing. The data showed that genes involved in embryonic organ development, pattern formation, branching morphogenesis, Wingless/Int signaling, and inflammation were differentially expressed in vitamin D-deficient mice. Network analysis suggested that differentially expressed genes were connected by the hubs matrix metallopeptidase 9; NF-κ light polypeptide gene enhancer in B cells inhibitor, α; epidermal growth factor receptor; and E1A binding protein p300. Given our findings that developmental pathways may be altered, we investigated if the timing of vitamin D exposure (in utero vs. postnatal) had an impact on lung health outcomes. Gene expression was measured in in utero or postnatal vitamin D-deficient mice, as well as whole-life vitamin D-deficient and -replete mice at 8 weeks of age. Baseline lung function, airway hyperresponsiveness, and airway inflammation were measured and lungs fixed for lung structure assessment using stereological methods and quantification of ASM mass. In utero vitamin D deficiency was sufficient to increase ASM mass and baseline airway resistance and alter lung structure. There were increased neutrophils but decreased lymphocytes in bronchoalveolar lavage. Expression of inflammatory molecules S100A9 and S100A8 was mainly increased in postnatal vitamin D-deficient mice. These observations suggest that in utero vitamin D deficiency can alter lung structure and function and increase inflammation, contributing to symptoms in chronic diseases, such as asthma. PMID:25867172

  14. Prioritizing risk factors to identify preventive interventions for economic assessment

    PubMed Central

    Blakely, Tony; Foster, Rachel H; Hadorn, David; Vos, Theo

    2012-01-01

    Abstract Objective To explore a risk factor approach for identifying preventive interventions that require more in-depth economic assessment, including cost-effectiveness analyses. Methods A three-step approach was employed to: (i) identify the risk factors that contribute most substantially to disability-adjusted life years (DALYs); (ii) re-rank these risk factors based on the availability of effective preventive interventions warranting further cost-effectiveness analysis (and in some instances on evidence from existing cost-effectiveness analyses); and (iii) re-rank these risk factors in accordance with their relative contribution to health inequalities. Health inequalities between the Māori and non-Māori populations in New Zealand were used by way of illustration. Findings Seven of the top 10 risk factors prioritized for research on preventive interventions in New Zealand were also among the 10 risk factors most highly ranked as contributing to DALYs in high-income countries of the World Health Organization’s Western Pacific Region. The final list of priority risk factors included tobacco use; alcohol use; high blood pressure; high blood cholesterol; overweight/obesity, and physical inactivity. All of these factors contributed to health inequalities. Effective interventions for preventing all of them are available, and for each risk factor there is at least one documented cost-saving preventive intervention. Conclusion The straightforward approach to prioritizing risk factors described in this paper may be applicable in many countries, and even in those countries that lack the capacity to perform additional cost-effectiveness analyses, this approach will still make it possible to determine which cost-effective interventions should be implemented in the short run. PMID:22423159

  15. Brief mechanical ventilation impacts airway cartilage properties in neonatal lambs

    PubMed Central

    Kim, Minwook; Pugarelli, Joan; Miller, Thomas L.; Wolfson, Marla R.; Dodge, George R.; Shaffer, Thomas H.

    2012-01-01

    Ultrasound imaging allows in vivo assessment of tracheal kinetics and cartilage structure. To date, the impact of mechanical ventilation (MV) on extracellular matrix (ECM) in airway cartilage is unclear, but an indication of its functional and structural change may support the development of protective therapies. The objective of this study was to characterize changes in mechanical properties of the neonatal airway during MV with alterations in cartilage ECM. Trachea segments were isolated in a neonatal lamb model; ultrasound dimensions and pressure-volume relationships were measured on sham (no MV; n = 6) and MV (n = 7) airways for 4 h. Tracheal cross-sections were harvested at 4 h, tissues were fixed and stained, and Fourier transform infrared imaging spectroscopy (FT-IRIS) was performed. Over 4 h of MV, bulk modulus (28%) and elastic modulus (282%) increased. The MV tracheae showed higher collagen, proteoglycan content, and collagen integrity (new tissue formation); whereas no changes were seen in the controls. These data are clinically relevant in that airway properties can be correlated with MV and changes in cartilage extracellular matrix. Mechanical ventilation increases the in vivo dimensions of the trachea, and is associated with evidence of airway tissue remodeling. Injury to the neonatal airway from MV may have relevance for the development of tracheomalacia. We demonstrated active airway tissue remodeling during MV using a FT-IRIS technique which identifies changes in ECM. PMID:22170596

  16. CT based computerized identification and analysis of human airways: A review

    PubMed Central

    Pu, Jiantao; Gu, Suicheng; Liu, Shusen; Zhu, Shaocheng; Wilson, David; Siegfried, Jill M.; Gur, David

    2012-01-01

    As one of the most prevalent chronic disorders, airway disease is a major cause of morbidity and mortality worldwide. In order to understand its underlying mechanisms and to enable assessment of therapeutic efficacy of a variety of possible interventions, noninvasive investigation of the airways in a large number of subjects is of great research interest. Due to its high resolution in temporal and spatial domains, computed tomography (CT) has been widely used in clinical practices for studying the normal and abnormal manifestations of lung diseases, albeit there is a need to clearly demonstrate the benefits in light of the cost and radiation dose associated with CT examinations performed for the purpose of airway analysis. Whereas a single CT examination consists of a large number of images, manually identifying airway morphological characteristics and computing features to enable thorough investigations of airway and other lung diseases is very time-consuming and susceptible to errors. Hence, automated and semiautomated computerized analysis of human airways is becoming an important research area in medical imaging. A number of computerized techniques have been developed to date for the analysis of lung airways. In this review, we present a summary of the primary methods developed for computerized analysis of human airways, including airway segmentation, airway labeling, and airway morphometry, as well as a number of computer-aided clinical applications, such as virtual bronchoscopy. Both successes and underlying limitations of these approaches are discussed, while highlighting areas that may require additional work. PMID:22559631

  17. CT based computerized identification and analysis of human airways: A review

    SciTech Connect

    Pu Jiantao; Gu Suicheng; Liu Shusen; Zhu Shaocheng; Wilson, David; Siegfried, Jill M.; Gur, David

    2012-05-15

    As one of the most prevalent chronic disorders, airway disease is a major cause of morbidity and mortality worldwide. In order to understand its underlying mechanisms and to enable assessment of therapeutic efficacy of a variety of possible interventions, noninvasive investigation of the airways in a large number of subjects is of great research interest. Due to its high resolution in temporal and spatial domains, computed tomography (CT) has been widely used in clinical practices for studying the normal and abnormal manifestations of lung diseases, albeit there is a need to clearly demonstrate the benefits in light of the cost and radiation dose associated with CT examinations performed for the purpose of airway analysis. Whereas a single CT examination consists of a large number of images, manually identifying airway morphological characteristics and computing features to enable thorough investigations of airway and other lung diseases is very time-consuming and susceptible to errors. Hence, automated and semiautomated computerized analysis of human airways is becoming an important research area in medical imaging. A number of computerized techniques have been developed to date for the analysis of lung airways. In this review, we present a summary of the primary methods developed for computerized analysis of human airways, including airway segmentation, airway labeling, and airway morphometry, as well as a number of computer-aided clinical applications, such as virtual bronchoscopy. Both successes and underlying limitations of these approaches are discussed, while highlighting areas that may require additional work.

  18. Bitter tasting compounds dilate airways by inhibiting airway smooth muscle calcium oscillations and calcium sensitivity

    PubMed Central

    Tan, Xiahui; Sanderson, Michael J

    2014-01-01

    Background and Purpose While selective, bitter tasting, TAS2R agonists can relax agonist-contracted airway smooth muscle (ASM), their mechanism of action is unclear. However, ASM contraction is regulated by Ca2+ signalling and Ca2+ sensitivity. We have therefore investigated how the TAS2R10 agonists chloroquine, quinine and denotonium regulate contractile agonist-induced Ca2+ signalling and sensitivity. Experimental Approach Airways in mouse lung slices were contracted with either methacholine (MCh) or 5HT and bronchodilation assessed using phase-contrast microscopy. Ca2+ signalling was measured with 2-photon fluorescence microscopy of ASM cells loaded with Oregon Green, a Ca2+-sensitive indicator (with or without caged-IP3). Effects on Ca2+ sensitivity were assessed on lung slices treated with caffeine and ryanodine to permeabilize ASM cells to Ca2+. Key Results The TAS2R10 agonists dilated airways constricted by either MCh or 5HT, accompanied by inhibition of agonist-induced Ca2+ oscillations. However, in non-contracted airways, TAS2R10 agonists, at concentrations that maximally dilated constricted airways, did not evoke Ca2+ signals in ASM cells. Ca2+ increases mediated by the photolysis of caged-IP3 were also attenuated by chloroquine, quinine and denotonium. In Ca2+-permeabilized ASM cells, the TAS2R10 agonists dilated MCh- and 5HT-constricted airways. Conclusions and Implications TAS2R10 agonists reversed bronchoconstriction by inhibiting agonist-induced Ca2+ oscillations while simultaneously reducing the Ca2+ sensitivity of ASM cells. Reduction of Ca2+ oscillations may be due to inhibition of Ca2+ release through IP3 receptors. Further characterization of bronchodilatory TAS2R agonists may lead to the development of novel therapies for the treatment of bronchoconstrictive conditions. PMID:24117140

  19. Brachycephalic airway syndrome.

    PubMed

    Meola, Stacy D

    2013-08-01

    Brachycephalic airway syndrome is a common finding in brachycephalic breeds. A combination of primary and secondary changes can progress to life-threatening laryngeal collapse. Early recognition of primary anatomic abnormalities that include stenotic nares, elongated soft palate, and hypoplastic trachea would allow the clinician to make early recommendations for medical and surgical management, which can improve the quality of life in affected animals. PMID:24182996

  20. Plasma exudation. Correlation between Evans blue dye and radiolabeled albumin in guinea pig airways in vivo

    SciTech Connect

    Rogers, D.F.; Boschetto, P.; Barnes, P.J. )

    1989-07-01

    We quantified the tissue exudation and luminal transudation of two plasma markers, Evans blue (EB) dye and ({sup 125}I)-human serum albumin (HSA), into the airways of the anesthetized guinea pig in response to platelet activating factor (PAF). There was a highly significant correlation between the tissue content of EB and ({sup 125}I)-HSA in all airways studied. Significant correlation for transudation of the two markers was limited to high rates of plasma leakage. ({sup 125}I)-HSA was the more sensitive marker for the association between exudation and transudation and the effect of PAF on transudation. EB was the better marker for assessing the relationship between the dose of PAF and plasma exudation.

  1. Upper airway resistance syndrome.

    PubMed

    Hasan, N; Fletcher, E C

    1998-07-01

    Many clinicians are familiar with the clinical symptoms and signs of obstructive sleep apnea (OSA). In its most blatant form, OSA is complete airway obstruction with repetitive, prolonged pauses in breathing, arterial oxyhemoglobin desaturation; followed by arousal with resumption of breathing. Daytime symptoms of this disorder include excessive daytime somnolence, intellectual dysfunction, and cardiovascular effects such as systemic hypertension, angina, myocardial infarction, and stroke. It has been recently recognized that increased pharyngeal resistance with incomplete obstruction can lead to a constellation of symptoms identical to OSA called "upper airway resistance syndrome" (UARS). The typical findings of UARS on sleep study are: (1) repetitive arousals from EEG sleep coinciding with a (2) waxing and waning of the respiratory airflow pattern and (3) increased respiratory effort as measured by esophageal pressure monitoring. There may be few, if any, obvious apneas or hypopneas with desaturation, but snoring may be a very prominent finding. Treatment with nasal positive airway pressure (NCPAP) eliminates the symptoms and confirms the diagnosis. Herein we describe two typical cases of UARS. PMID:9676067

  2. Airway closure in microgravity.

    PubMed

    Dutrieue, Brigitte; Verbanck, Sylvia; Darquenne, Chantal; Prisk, G Kim

    2005-08-25

    Recent single breath washout (SBW) studies in microgravity and on the ground have suggested an important effect of airway closure on gas mixing in the human lung, reflected particularly in the phase III slope of vital capacity SBW and bolus tests. In order to explore this effect, we designed a SBW in which subjects inspired 2-l from residual volume (RV) starting with a 150 ml bolus of He and SF6. In an attempt to vary the pattern of airways closure configuration before the test, the experiments were conducted in 1G and in microgravity during parabolic flight allowing the pre-test expiration to RV to be either in microgravity or at 1.8 G, with the actual test gas inhalation performed entirely in microgravity. Contrary to our expectations, the measured phase III slope and phase IV height and volume obtained from seven subjects in microgravity were essentially identical irrespective of the gravity level during the pre-test expiration to RV. The results suggest that airway closure configuration at RV before the test inspiration has no apparent impact on phases III and IV generation. PMID:15979418

  3. LIGHT is a crucial mediator of airway remodeling.

    PubMed

    Hung, Jen-Yu; Chiang, Shyh-Ren; Tsai, Ming-Ju; Tsai, Ying-Ming; Chong, Inn-Wen; Shieh, Jiunn-Min; Hsu, Ya-Ling

    2015-05-01

    Chronic inflammatory airway diseases like asthma and chronic obstructive pulmonary disease are major health problems globally. Airway epithelial cells play important role in airway remodeling, which is a critical process in the pathogenesis of diseases. This study aimed to demonstrate that LIGHT, an inflammatory factor secreted by T cells after allergen exposure, is responsible for promoting airway remodeling. LIGHT increased primary human bronchial epithelial cells (HBECs) undergoing epithelial-mesenchymal transition (EMT) and expressing MMP-9. The induction of EMT was associated with increased NF-κB activation and p300/NF-κB association. The interaction of NF-κB with p300 facilitated NF-κB acetylation, which in turn, was bound to the promoter of ZEB1, resulting in E-cadherin downregulation. LIGHT also stimulated HBECs to produce numerous cytokines/chemokines that could worsen airway inflammation. Furthermore, LIGHT enhanced HBECs to secrete activin A, which increased bronchial smooth muscle cell (BSMC) migration. In contrast, depletion of activin A decreased such migration. The findings suggest a new molecular determinant of LIGHT-mediated pathogenic changes in HBECs and that the LIGHT-related vicious cycle involving HBECs and BSMCs may be a potential target for the treatment of chronic inflammation airway diseases with airway remodeling. PMID:25251281

  4. Long-Acting Beta Agonists Enhance Allergic Airway Disease

    PubMed Central

    Knight, John M.; Mak, Garbo; Shaw, Joanne; Porter, Paul; McDermott, Catherine; Roberts, Luz; You, Ran; Yuan, Xiaoyi; Millien, Valentine O.; Qian, Yuping; Song, Li-Zhen; Frazier, Vincent; Kim, Choel; Kim, Jeong Joo; Bond, Richard A.; Milner, Joshua D.; Zhang, Yuan; Mandal, Pijus K.; Luong, Amber; Kheradmand, Farrah

    2015-01-01

    Asthma is one of the most common of medical illnesses and is treated in part by drugs that activate the beta-2-adrenoceptor (β2-AR) to dilate obstructed airways. Such drugs include long acting beta agonists (LABAs) that are paradoxically linked to excess asthma-related mortality. Here we show that LABAs such as salmeterol and structurally related β2-AR drugs such as formoterol and carvedilol, but not short-acting agonists (SABAs) such as albuterol, promote exaggerated asthma-like allergic airway disease and enhanced airway constriction in mice. We demonstrate that salmeterol aberrantly promotes activation of the allergic disease-related transcription factor signal transducer and activator of transcription 6 (STAT6) in multiple mouse and human cells. A novel inhibitor of STAT6, PM-242H, inhibited initiation of allergic disease induced by airway fungal challenge, reversed established allergic airway disease in mice, and blocked salmeterol-dependent enhanced allergic airway disease. Thus, structurally related β2-AR ligands aberrantly activate STAT6 and promote allergic airway disease. This untoward pharmacological property likely explains adverse outcomes observed with LABAs, which may be overcome by agents that antagonize STAT6. PMID:26605551

  5. Long-Acting Beta Agonists Enhance Allergic Airway Disease.

    PubMed

    Knight, John M; Mak, Garbo; Shaw, Joanne; Porter, Paul; McDermott, Catherine; Roberts, Luz; You, Ran; Yuan, Xiaoyi; Millien, Valentine O; Qian, Yuping; Song, Li-Zhen; Frazier, Vincent; Kim, Choel; Kim, Jeong Joo; Bond, Richard A; Milner, Joshua D; Zhang, Yuan; Mandal, Pijus K; Luong, Amber; Kheradmand, Farrah; McMurray, John S; Corry, David B

    2015-01-01

    Asthma is one of the most common of medical illnesses and is treated in part by drugs that activate the beta-2-adrenoceptor (β2-AR) to dilate obstructed airways. Such drugs include long acting beta agonists (LABAs) that are paradoxically linked to excess asthma-related mortality. Here we show that LABAs such as salmeterol and structurally related β2-AR drugs such as formoterol and carvedilol, but not short-acting agonists (SABAs) such as albuterol, promote exaggerated asthma-like allergic airway disease and enhanced airway constriction in mice. We demonstrate that salmeterol aberrantly promotes activation of the allergic disease-related transcription factor signal transducer and activator of transcription 6 (STAT6) in multiple mouse and human cells. A novel inhibitor of STAT6, PM-242H, inhibited initiation of allergic disease induced by airway fungal challenge, reversed established allergic airway disease in mice, and blocked salmeterol-dependent enhanced allergic airway disease. Thus, structurally related β2-AR ligands aberrantly activate STAT6 and promote allergic airway disease. This untoward pharmacological property likely explains adverse outcomes observed with LABAs, which may be overcome by agents that antagonize STAT6. PMID:26605551

  6. Upper Airway Elasticity Estimation in Pediatric Down Syndrome Sleep Apnea Patients Using Collapsible Tube Theory.

    PubMed

    Subramaniam, Dhananjay Radhakrishnan; Mylavarapu, Goutham; McConnell, Keith; Fleck, Robert J; Shott, Sally R; Amin, Raouf S; Gutmark, Ephraim J

    2016-05-01

    Elasticity of the soft tissues surrounding the upper airway lumen is one of the important factors contributing to upper airway disorders such as snoring and obstructive sleep apnea. The objective of this study is to calculate patient specific elasticity of the pharynx from magnetic resonance (MR) images using a 'tube law', i.e., the relationship between airway cross-sectional area and transmural pressure difference. MR imaging was performed under anesthesia in children with Down syndrome (DS) and obstructive sleep apnea (OSA). An airway segmentation algorithm was employed to evaluate changes in airway cross-sectional area dilated by continuous positive airway pressure (CPAP). A pressure-area relation was used to make localized estimates of airway wall stiffness for each patient. Optimized values of patient specific Young's modulus for tissue in the velopharynx and oropharynx, were estimated from finite element simulations of airway collapse. Patient specific deformation of the airway wall under CPAP was found to exhibit either a non-linear 'hardening' or 'softening' behavior. The localized airway and tissue elasticity were found to increase with increasing severity of OSA. Elasticity based patient phenotyping can potentially assist clinicians in decision making on CPAP and airway or tissue elasticity can supplement well-known clinical measures of OSA severity. PMID:26314989

  7. Drought Risk Assessment based on Natural and Social Factors

    NASA Astrophysics Data System (ADS)

    Huang, Jing; Wang, Huimin; Han, Dawei

    2015-04-01

    In many parts of the world, drought hazard is becoming more frequent and severe due to climate change and human activities. It is crucial to monitor and assess drought conditions, especially for decision making support in agriculture sector. The vegetation index (VI) decreases, and the land surface temperature (LST) increases when the vegetation is under drought stress. Therefore both of these remotely sensed indices are widely used in drought monitoring and assessment. Temperature-Vegetation Dryness Index (TVDI) is obtained by establishing the feature space of the normalized difference vegetation index (NDVI) and LST, which reflects agriculture dry situation by inverting soil moisture. However, these indices only concern the natural hazard-causing factors. Our society is a complex large-scale system with various natural and social elements. The drought risk is the joint consequence of hazard-causing factors and hazard-affected bodies. For example, as the population increases, the exposure of the hazard-affected bodies also tends to increase. The high GDP enhances the response ability of government, and the irrigation and water conservancy reduces the vulnerability. Such characteristics of hazard-affected bodies should be coupled with natural factors. In this study, the 16-day moderate-resolution imaging spectroradiometer (MODIS) NDVI and LST data are combined to establish NDVI-Ts space according to different land use types in Yunnan Province, China. And then, TVDIs are calculated through dry and wet edges modeled as a linear fit to data for each land cover type. Next, the efforts are turned to establish an integrated drought assessment index of social factors and TVDI through ascertaining attribute weight based on rough sets theory. Thus, the new CDI (comprehensive drought index) recorded during spring of 2010 and the spatial variations in drought are analyzed and compared with TVDI dataset. Moreover, actual drought risk situation in the study area is given to

  8. Permanent respiratory impairment and upper airway symptoms despite clinical improvement in patients with reactive airways dysfunction syndrome.

    PubMed

    Demeter, S L; Cordasco, E M; Guidotti, T L

    2001-04-10

    We previously reported clinical findings for 19 patients who developed symptomatic airways hyperactivity following an acute exposure to an inhaled irritant and who were given the diagnosis of reactive airways dysfunction syndrome (RADS). We now report on nine of these patients who have been followed for a mean of 9 years, allowing assessment of function, symptoms, and comorbidity beyond the early phase of acute airway injury and inflammation. None of the patients have resolved their airway hyper-responsiveness and symptoms completely, although only in one subject, who had a premorbid history of asthma, has the condition progressed. A common feature has been sinusitis and other upper-airway symptoms. We conclude that in this group of patients, RADS presented in a consistent pattern regardless of the cause of airway injury, resolved only partially, even in subjects without a premorbid history of respiratory disease, and was associated with significant secondary morbidity, especially affecting the upper airway. This pattern was evident regardless of smoking status or age at time of exposure. We conclude that for these subjects, RADS was a distinct entity with a consistent natural history that conferred permanent impairment, but did generally improve somewhat over time. PMID:11327398

  9. Transcription factor motif quality assessment requires systematic comparative analysis

    PubMed Central

    Kibet, Caleb Kipkurui; Machanick, Philip

    2016-01-01

    Transcription factor (TF) binding site prediction remains a challenge in gene regulatory research due to degeneracy and potential variability in binding sites in the genome. Dozens of algorithms designed to learn binding models (motifs) have generated many motifs available in research papers with a subset making it to databases like JASPAR, UniPROBE and Transfac. The presence of many versions of motifs from the various databases for a single TF and the lack of a standardized assessment technique makes it difficult for biologists to make an appropriate choice of binding model and for algorithm developers to benchmark, test and improve on their models. In this study, we review and evaluate the approaches in use, highlight differences and demonstrate the difficulty of defining a standardized motif assessment approach. We review scoring functions, motif length, test data and the type of performance metrics used in prior studies as some of the factors that influence the outcome of a motif assessment. We show that the scoring functions and statistics used in motif assessment influence ranking of motifs in a TF-specific manner. We also show that TF binding specificity can vary by source of genomic binding data. We also demonstrate that information content of a motif is not in isolation a measure of motif quality but is influenced by TF binding behaviour. We conclude that there is a need for an easy-to-use tool that presents all available evidence for a comparative analysis. PMID:27092243

  10. Assessing Protective Factors of Youth Who Sexually Offended in Singapore

    PubMed Central

    Chu, Chi Meng; Lee, Yirong

    2015-01-01

    Sexual offending has attracted increasing public concern because of its long-term effects. Although there is an increasing amount of research on the risk factors for recidivism among youth who have sexually offended, there is a dearth of research on the protective factors for desistence from recidivism. The current study investigated the associations between protective factors and recidivism among 97 Singaporean youth who sexually offended (YSO). In addition, the predictive validity with regard to two new measures of protective factors—the Desistence for Adolescents Who Sexually Harm (DASH-13), and Structured Assessment of Protective Factors for Violence Risk (SAPROF)—were also evaluated. Results indicated that both the DASH-13 and the SAPROF were inversely related to the Estimate of Risk of Adolescent Sexual Offense Recidivism (ERASOR). However, neither the DASH-13 nor the SAPROF were found to have adequate predictive validity or incremental validity for sexual or nonsexual recidivism. The implications for the assessment and management of YSO are discussed. PMID:25527632

  11. Increased Th2 cytokine secretion, eosinophilic airway inflammation, and airway hyperresponsiveness in neurturin-deficient mice.

    PubMed

    Michel, Tatiana; Thérésine, Maud; Poli, Aurélie; Domingues, Olivia; Ammerlaan, Wim; Brons, Nicolaas H C; Hentges, François; Zimmer, Jacques

    2011-06-01

    Neurotrophins such as nerve growth factor and brain-derived neurotrophic factor have been described to be involved in the pathogenesis of asthma. Neurturin (NTN), another neurotrophin from the glial cell line-derived neurotrophic factor family, was shown to be produced by human immune cells: monocytes, B cells, and T cells. Furthermore, it was previously described that the secretion of inflammatory cytokines was dramatically stimulated in NTN knockout (NTN(-/-)) mice. NTN is structurally similar to TGF-β, a protective cytokine in airway inflammation. This study investigates the implication of NTN in a model of allergic airway inflammation using NTN(-/-) mice. The bronchial inflammatory response of OVA-sensitized NTN(-/-) mice was compared with wild-type mice. Airway inflammation, Th2 cytokines, and airway hyperresponsiveness (AHR) were examined. NTN(-/-) mice showed an increase of OVA-specific serum IgE and a pronounced worsening of inflammatory features. Eosinophil number and IL-4 and IL-5 concentration in the bronchoalveolar lavage fluid and lung tissue were increased. In parallel, Th2 cytokine secretion of lung draining lymph node cells was also augmented when stimulated by OVA in vitro. Furthermore, AHR was markedly enhanced in NTN(-/-) mice after sensitization and challenge when compared with wild-type mice. Administration of NTN before challenge with OVA partially rescues the phenotype of NTN(-/-) mice. These findings provide evidence for a dampening role of NTN on allergic inflammation and AHR in a murine model of asthma. PMID:21508262

  12. Management of the artificial airway.

    PubMed

    Branson, Richard D; Gomaa, Dina; Rodriquez, Dario

    2014-06-01

    Management of the artificial airway includes securing the tube to prevent dislodgement or migration as well as removal of secretions. Preventive measures include adequate humidification and appropriate airway suctioning. Monitoring airway patency and removing obstruction are potentially life-saving components of airway management. Cuff pressure management is important for preventing aspiration and mucosal damage as well as assuring adequate ventilation. A number of new monitoring techniques have been introduced, and automated cuff pressure control is becoming more common. The respiratory therapist should be adept with all these devices and understand the appropriate application and management. PMID:24891202

  13. CT Metrics of Airway Disease and Emphysema in Severe COPD

    PubMed Central

    Kim, Woo Jin; Silverman, Edwin K.; Hoffman, Eric; Criner, Gerard J.; Mosenifar, Zab; Sciurba, Frank C.; Make, Barry J.; Carey, Vincent; Estépar, Raúl San José; Diaz, Alejandro; Reilly, John J.; Martinez, Fernando J.; Washko, George R.

    2009-01-01

    Background: CT scan measures of emphysema and airway disease have been correlated with lung function in cohorts of subjects with a range of COPD severity. The contribution of CT scan-assessed airway disease to objective measures of lung function and respiratory symptoms such as dyspnea in severe emphysema is less clear. Methods: Using data from 338 subjects in the National Emphysema Treatment Trial (NETT) Genetics Ancillary Study, densitometric measures of emphysema using a threshold of −950 Hounsfield units (%LAA-950) and airway wall phenotypes of the wall thickness (WT) and the square root of wall area (SRWA) of a 10-mm luminal perimeter airway were calculated for each subject. Linear regression analysis was performed for outcome variables FEV1 and percent predicted value of FEV1 with CT scan measures of emphysema and airway disease. Results: In univariate analysis, there were significant negative correlations between %LAA-950 and both the WT (r = −0.28, p = 0.0001) and SRWA (r = −0.19, p = 0.0008). Airway wall thickness was weakly but significantly correlated with postbronchodilator FEV1% predicted (R = −0.12, p = 0.02). Multivariate analysis showed significant associations between either WT or SRWA (β = −5.2, p = 0.009; β = −2.6, p = 0.008, respectively) and %LAA-950 (β = −10.6, p = 0.03) with the postbronchodilator FEV1% predicted. Male subjects exhibited significantly thicker airway wall phenotypes (p = 0.007 for WT and p = 0.0006 for SRWA). Conclusions: Airway disease and emphysema detected by CT scanning are inversely related in patients with severe COPD. Airway wall phenotypes were influenced by gender and associated with lung function in subjects with severe emphysema. PMID:19411295

  14. Trigger of bronchial hyperresponsiveness development may not always need eosinophilic airway inflammation in very early stage of asthma

    PubMed Central

    Obase, Yasushi; Kishikawa, Reiko; Kohno, Shigeru; Iwanaga, Tomoaki

    2016-01-01

    Background: Cough variant asthma (CVA), a suggested precursor of standard bronchial asthma (SBA), is characterized by positive bronchial hyperresponsiveness (BHR) and a chronic cough response to bronchodilator that persists for >8 weeks. Objective: Airway inflammation, BHR, and airway obstructive damage were analyzed to assess whether CVA represents early or mild-stage SBA. Methods: Patients with newly diagnosed CVA (n = 72) and SBA (n = 84) naive to oral or inhaled corticosteroids and without exacerbated asthma were subjected to spirometry, impulse oscillometry, BHR tests, sputum induction, and fractional exhaled nitric oxide measurements. Results: In the patients with CVA, spirometry demonstrated higher forced expiratory volume in 1 second (FEV1) to forced vital capacity ratio, FEV1 percent predicted, flow volume at 50% of vital capacity % predicted, and flow volume at 25% of vital capacity % predicted values, and impulse oscillometry demonstrated lower R5–Z20, AX, and Fres, and higher X5 values. In addition, the fractional exhaled nitric oxide and sputum eosinophil numbers were lower and the PC20 was higher than in patients with moderate SBA. However, these factors were similar in the patients with CVA and in the patients with intermittent mild SBA. A significantly smaller proportion of the patients with CVA had increased sputum eosinophils than the patients with intermittent mild SBA (p < 0.0001). However, interestingly, among the patients with CVA, no significant differences in the PC20 values were found between the patients with and those without increased sputum eosinophils. Conclusions: All measures of central and peripheral airway obstruction, eosinophilic inflammation, and airway hyperresponsiveness in patients with CVA were milder than in patients with moderate SBA but were similar to those of patients with intermittent mild SBA. In CVA, the BHR was not affected by airway eosinophilic inflammation, which indicated that the very early development of BHR

  15. Effect of heparin and a low-molecular weight heparinoid on PAF-induced airway responses in neonatally immunized rabbits.

    PubMed Central

    Sasaki, M.; Herd, C. M.; Page, C. P.

    1993-01-01

    1. We have investigated the effect of an unfractionated heparin preparation, a low-molecular weight heparinoid (Org 10172) and the polyanionic molecule polyglutamic acid against PAF-induced airway hyperresponsiveness and pulmonary cell infiltration in neonatally immunized rabbits in vivo. 2. Exposure of neonatally immunized rabbits to aerosolized platelet activating factor (PAF) (80 micrograms ml-1 for 60 min) elicited an increase in airway responsiveness to inhaled histamine 24 h and 72 h following challenge which was associated with an infiltration of inflammatory cells into the airways, as assessed by bronchoalveolar lavage (BAL). 3. A significant increase in the total numbers of cells recovered from BAL fluid was associated with significantly increased cell numbers of neutrophils, eosinophils and mononuclear cells 24 h following PAF exposure. The numbers of eosinophils and neutrophils in the airways remained elevated 72 h after challenge. 4. The intravenous administration of an unfractionated preparation of heparin (100 units kg-1) or Org 10172 (100 micrograms kg-1) 30 min prior to PAF exposure significantly inhibited the airway hyperresponsiveness induced by PAF, 24 h and 72 h following challenge. PAF-induced hyperresponsiveness was not significantly affected by prior intravenous administration of polyglutamic acid (100 micrograms kg-1). 5. The intravenous administration of unfractionated heparin (100 units kg-1), Org 10172 (100 micrograms kg-1) or polyglutamic acid (100 micrograms kg-1) 30 min prior to PAF exposure significantly inhibited the expected increase in total cell infiltration. 6. This study shows that unfractionated heparin and a low-molecular weight heparinoid, Org 10172, are capable of inhibiting both the airway hyperresponsiveness and pulmonary cell infiltration induced by PAF in the rabbit. PMID:7693273

  16. Factors Associated with Men's Assessment of Prostate Cancer Treatment Choice.

    PubMed

    Ross, Louie E; Howard, Daniel L; Bowie, Janice V; Thorpe, Roland J; Kinlock, Ballington L; Burt, Carol; LaVeist, Thomas A

    2016-06-01

    The objective of this study is to examine factors among a group of African American and White men in North Carolina and their assessment of prostate cancer treatment choice or belief that treatment chosen was best. A sample of men (N = 877) with a history of prostate cancer diagnosis was recruited from the North Carolina Cancer Registry during 2007-2008 and asked to participate in a telephone interview covering several measures about their initial prostate cancer treatment. Logistic regression was used to assess demographic, psychosocial, and clinical factors on whether they felt that they had chosen the best treatment for the disease. Respondents were majority White (52.7 %), married (75.9 %), and had surgery (67.9 %) as their initial treatment. At the bivariate level, factors associated with the belief that the treatment chosen was best were as follows: White race/ethnicity, higher levels of education, a more recent treatment date, having health insurance coverage, type of treatment received, higher levels of bother from side effects, greater contentment with their quality of life, and doctor discussions of the various treatment options. Similarly, the multivariate analysis showed increased odds of belief that the treatment chosen was the best among demographic (i.e., race/ethnicity, level of education, and health insurance coverage) as well as psychosocial and clinical variables (i.e., greater bother from side effects, greater contentment with their quality of life, and initial treatment received). Results suggest that demographic, psychosocial, and clinical factors play an important role for men in assessing their treatment choices for prostate cancer. PMID:25893926

  17. Exercise and airway injury in athletes.

    PubMed

    Couto, Mariana; Silva, Diana; Delgado, Luis; Moreira, André

    2013-01-01

    Olympic level athletes present an increased risk for asthma and allergy, especially those who take part in endurance sports, such as swimming or running, and in winter sports. Classical postulated mechanisms behind EIA include the osmotic, or airway-drying, hypothesis. Hyperventilation leads to evaporation of water and the airway surface liquid becomes hyperosmolar, providing a stimulus for water to move from any cell nearby, which results in the shrinkage of cells and the consequent release of inflammatory mediators that cause airway smooth muscle contraction. But the exercise-induced asthma/bronchoconstriction explanatory model in athletes probably comprises the interaction between environmental training factors, including allergens and ambient conditions such as temperature, humidity and air quality; and athlete's personal risk factors, such as genetic and neuroimmuneendocrine determinants. After the stress of training and competitions athletes experience higher rate of upper respiratory tract infections (URTI), compared with lesser active individuals. Increasing physical activity in non-athletes is associated with a decreased risk of URTI. Heavy exercise induces marked immunodepression which is multifactorial in origin. Prolonged, high intensity exercise temporarily impairs the immune competence while moderate activity may enhance immune function. The relationship between URTI and exercise is affected by poorly known individual determinants such genetic susceptibility, neurogenic mediated immune inflammation and epithelial barrier dysfunction. Further studies should better define the aetiologic factors and mechanisms involved in the development of asthma in athletes, and propose relevant preventive and therapeutic measures. PMID:23697359

  18. Incidence of unanticipated difficult airway in obstetric patients in a teaching institution.

    PubMed

    Tao, Weike; Edwards, Jason T; Tu, Faping; Xie, Yang; Sharma, Shiv K

    2012-01-31

    PURPOSE: Our aim was to determine the incidence of difficult intubation during pregnancy-related surgery at a high-risk, high-volume teaching institution. METHODS: Airway experience was analyzed among patients who had pregnancy-related surgery under general anesthesia from January 2001 through February 2006. A difficult airway was defined as needing three or more direct laryngoscopy (DL) attempts, use of the additional airway equipment after the DL attempts, or conversion to regional anesthesia due to inability to intubate. Airway characteristics were compared between patients with and without a difficult airway. In addition, pre- and postoperative airway evaluations were compared to identify factors closely related to changes from pregnancy. RESULTS: In a total of 30,766 operations, 2,158 (7%) were performed with general anesthesia. Among these, 1,026 (47.5%) were for emergency cesarean delivery (CD), 610 (28.3%) for nonemergency CD, and 522 (24.2%) for non-CD procedures. A total of 12 patients (0.56%) were identified as having a difficult airway. Four patients were intubated with further DL attempts; others required mask ventilation and other airway equipment. Two patients were ventilated through a laryngeal mask airway without further intubation attempts. Ten of the 12 difficult airway cases were encountered by residents during their first year of clinical anesthesia training. There were no maternal or fetal complications except one possible aspiration. CONCLUSION: Unanticipated difficult airways accounted for 0.56% of all pregnancy-related surgical patients. More than 99.9% of all obstetric patients could be intubated. A difficult airway is more likely to be encountered by anesthesia providers with <1 year of experience. Proper use of airway equipment may help secure the obstetric airway or provide adequate ventilation. Emergency CD did not add an additional level of difficulty over nonemergency CD. PMID:22290734

  19. Air-Q intubating laryngeal airway: A study of the second generation supraglottic airway device

    PubMed Central

    Attarde, Viren Bhaskar; Kotekar, Nalini; Shetty, Sarika M

    2016-01-01

    Background and Aims: Air-Q intubating laryngeal mask airway (ILA) is used as a supraglottic airway device and as a conduit for endotracheal intubation. This study aims to assess the efficacy of the Air-Q ILA regarding ease of insertion, adequacy of ventilation, rate of successful intubation, haemodynamic response and airway morbidity. Methods: Sixty patients presenting for elective surgery at our Medical College Hospital were selected. Following adequate premedication, baseline vital parameters, pulse rate and blood pressure were recorded. Air-Q size 3.5 for patients 50-70 kg and size 4.5 for 70-100 kg was selected. After achieving adequate intubating conditions, Air-Q ILA was introduced. Confirming adequate ventilation, appropriate sized endotracheal tube was advanced through the Air-Q blindly to intubate the trachea. Placement of the endotracheal tube in trachea was confirmed. Results: Air-Q ILA was successfully inserted in 88.3% of patients in first attempt and 11.7% patients in second attempt. Ventilation was adequate in 100% of patients. Intubation was successful in 76.7% of patients with Air-Q ILA. 23.3% of patients were intubated by direct laryngoscopy following failure with two attempts using Air-Q ILA. Post-intubation the change in heart rate was statistically significant (P < 0.0001). 10% of patients were noted to have a sore throat and 5% of patients had mild airway trauma. Conclusion: Air-Q ILA is a reliable device as a supraglottic airway ensuring adequate ventilation as well as a conduit for endotracheal intubation. It benefits the patient by avoiding the stress of direct laryngoscopy and is also superior alternative device for use in a difficult airway. PMID:27212722

  20. 21 CFR 868.5110 - Oropharyngeal airway.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5110 Oropharyngeal airway. (a... provide a patent airway. (b) Classification. Class I (general controls). The device is exempt from...

  1. 21 CFR 868.5110 - Oropharyngeal airway.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5110 Oropharyngeal airway. (a... provide a patent airway. (b) Classification. Class I (general controls). The device is exempt from...

  2. Control of local immunity by airway epithelial cells.

    PubMed

    Weitnauer, M; Mijošek, V; Dalpke, A H

    2016-03-01

    The lung is ventilated by thousand liters of air per day. Inevitably, the respiratory system comes into contact with airborne microbial compounds, most of them harmless contaminants. Airway epithelial cells are known to have innate sensor functions, thus being able to detect microbial danger. To avoid chronic inflammation, the pulmonary system has developed specific means to control local immune responses. Even though airway epithelial cells can act as proinflammatory promoters, we propose that under homeostatic conditions airway epithelial cells are important modulators of immune responses in the lung. In this review, we discuss epithelial cell regulatory functions that control reactivity of professional immune cells within the microenvironment of the airways and how these mechanisms are altered in pulmonary diseases. Regulation by epithelial cells can be divided into two mechanisms: (1) mediators regulate epithelial cells' innate sensitivity in cis and (2) factors are produced that limit reactivity of immune cells in trans. PMID:26627458

  3. Vehicle emission unit risk factors for transportation risk assessments

    SciTech Connect

    Biwer, B.M.; Butler, J.P.

    1999-12-01

    When the transportation risk posed by shipments of hazardous chemical and radioactive materials is being assessed, it is necessary to evaluate the risks associated with both vehicle emissions and cargo-related risks. Diesel exhaust and fugitive dust emissions from vehicles transporting hazardous shipments lead to increased air pollution, which increases the risk of latent fatalities in the affected population along the transport route. The estimated risk from these vehicle-related sources can often by as large or larger than the estimated risk associated with the material being transported. In this paper, data from the US Environmental Protection Agency's Motor Vehicle-Related Air Toxics Study are first used to develop latent cancer fatality estimates per kilometer of travel in rural and urban areas for all diesel truck classes. These unit risk factors are based on studies investigating the carcinogenic nature of diesel exhaust. With the same methodology, the current per=kilometer latent fatality risk factor used in transportation risk assessment for heavy diesel trucks in urban areas is revised and the analysis expanded to provide risk factors for rural areas and all diesel truck classes. These latter fatality estimates may include, but are not limited to, cancer fatalities and are based primarily on the most recent epidemiological data available on mortality rates associated with ambient air PM-10 concentrations.

  4. Vehicle emission unit risk factors for transportation risk assessments.

    PubMed

    Biwer, B M; Butler, J P

    1999-12-01

    When the transportation risk posed by shipments of hazardous chemical and radioactive materials is being assessed, it is necessary to evaluate the risks associated with both vehicle emissions and cargo-related risks. Diesel exhaust and fugitive dust emissions from vehicles transporting hazardous shipments lead to increased air pollution, which increases the risk of latent fatalities in the affected population along the transport route. The estimated risk from these vehicle-related sources can often be as large or larger than the estimated risk associated with the material being transported. In this paper, data from the U.S. Environmental Protection Agency's Motor Vehicle-Related Air Toxics Study are first used to develop latent cancer fatality estimates per kilometer of travel in rural and urban areas for all diesel truck classes. These unit risk factors are based on studies investigating the carcinogenic nature of diesel exhaust. With the same methodology, the current per-kilometer latent fatality risk factor used in transportation risk assessments for heavy diesel trucks in urban areas is revised and the analysis expanded to provide risk factors for rural areas and all diesel truck classes. These latter fatality estimates may include, but are not limited to, cancer fatalities and are based primarily on the most recent epidemiological data available on mortality rates associated with ambient air PM-10 concentrations. PMID:10765454

  5. Review article: Extubation of the difficult airway and extubation failure.

    PubMed

    Cavallone, Laura F; Vannucci, Andrea

    2013-02-01

    Respiratory complications after tracheal extubation are associated with significant morbidity and mortality, suggesting that process improvements in this clinical area are needed. The decreased rate of respiratory adverse events occurring during tracheal intubation since the implementation of guidelines for difficult airway management supports the value of education and guidelines in advancing clinical practice. Accurate use of terms in defining concepts and describing distinct clinical conditions is paramount to facilitating understanding and fostering education in the treatment of tracheal extubation-related complications. As an example, understanding the distinction between extubation failure and weaning failure allows one to appreciate the need for pre-extubation tests that focus on assessing airway patency in addition to evaluating the ability to breathe spontaneously. Tracheal reintubation after planned extubation is a relatively rare event in the postoperative period of elective surgeries, with reported rates of reintubation in the operating room and postanesthesia care unit between 0.1% and 0.45%, but is a fairly common event in critically ill patients (0.4%-25%). Conditions such as obesity, obstructive sleep apnea, major head/neck and upper airway surgery, and obstetric and cervical spine procedures carry significantly increased risks of extubation failure and are frequently associated with difficult airway management. Extubation failure follows loss of upper airway patency. Edema, soft tissue collapse, and laryngospasm are among the most frequent mechanisms of upper airway obstruction. Planning for tracheal extubation is a critical component of a successful airway management strategy, particularly when dealing with situations at increased risk for extubation failure and in patients with difficult airways. Adequate planning requires identification of patients who have or may develop a difficult airway, recognition of situations at increased risk of

  6. Continuous positive airway pressure: Physiology and comparison of devices.

    PubMed

    Gupta, Samir; Donn, Steven M

    2016-06-01

    Nasal continuous positive airway pressure (CPAP) is increasingly used for respiratory support in preterm babies at birth and after extubation from mechanical ventilation. Various CPAP devices are available for use that can be broadly grouped into continuous flow and variable flow. There are potential physiologic differences between these CPAP systems and the choice of a CPAP device is too often guided by individual expertise and experience rather than by evidence. When interpreting the evidence clinicians should take into account the pressure generation sources, nasal interface, and the factors affecting the delivery of pressure, such as mouth position and respiratory drive. With increasing use of these devices, better monitoring techniques are required to assess the efficacy and early recognition of babies who are failing and in need of escalated support. PMID:26948884

  7. Brachycephalic airway obstructive syndrome.

    PubMed

    Wykes, P M

    1991-06-01

    This is a complex condition, recognized primarily in brachycephalic breeds, that results in varying degrees of upper airway obstruction. The signs consist of respiratory distress, stridor, reduced exercise tolerance, and in more severe cases, cyanosis and collapse. The inherent anatomy of the brachycephalic skull contributes to the development of these signs. Such anatomic features include: a shortened and distorted nasopharynx, stenotic nares, an elongated soft palate, and everted laryngeal saccules. The increased negative pressure created in the pharyngolaryngeal region, as a result of these obstructing structures, ultimately results in distortion and collapse of the arytenoid cartilages of the larynx. PMID:1802247

  8. Particle Deposition During Airway Closure

    NASA Astrophysics Data System (ADS)

    Tai, Cheng-Feng; Halpern, David; Grotberg, James B.

    2011-11-01

    Inhaled aerosol particles deposit in the lung and may be from environmental, toxic, or medical therapy sources. While much research focuses on inspiratory deposition, primarily at airway bifurcations due to inertial impaction, there are other mechanisms that allow the particles to reach the airway surface, such as gravitational settling and diffusion depending on particle size. We introduce a new mechanism not previously studied, i.e. aerosol deposition from airway closure. The airways are lined with a liquid layer. Due to the surface tension driven instability, a liquid plug can form from this layer which blocks the airway. This process of airway closure tends to occur toward the end of expiration. In this study, the efficiency of the impaction of the particles during airway closure will be investigated. The particles will be released from the upstream of the airway and convected by the air flow and deposited onto the closing liquid layer. We solve the governing equations using a finite volume approach in conjunction with a sharp interface method for the interfaces. Once the velocity field of the gas flow is obtained, the path of the particles will be calculated and the efficiency of the deposition can be estimated. We acknowledge support from the National Institutes of Health grant number NIH HL85156.

  9. Operative endoscopy of the airway

    PubMed Central

    Walters, Dustin M.

    2016-01-01

    Airway endoscopy has long been an important and useful tool in the management of thoracic diseases. As thoracic specialists have gained experience with both flexible and rigid bronchoscopic techniques, the technology has continued to evolve so that bronchoscopy is currently the foundation for diagnosis and treatment of many thoracic ailments. Airway endoscopy plays a significant role in the biopsy of tumors within the airways, mediastinum, and lung parenchyma. Endoscopic methods have been developed to treat benign and malignant airway stenoses and tracheomalacia. And more recently, techniques have been conceived to treat end-stage emphysema and prolonged air leaks in select patients. This review describes the abundant uses of airway endoscopy, as well as technical considerations and limitations of the current technologies. PMID:26981263

  10. Compliance Measurements of the Upper Airway in Pediatric Down Syndrome Sleep Apnea Patients.

    PubMed

    Subramaniam, Dhananjay Radhakrishnan; Mylavarapu, Goutham; McConnell, Keith; Fleck, Robert J; Shott, Sally R; Amin, Raouf S; Gutmark, Ephraim J

    2016-04-01

    Compliance of soft tissue and muscle supporting the upper airway are two of several factors contributing to pharyngeal airway collapse. We present a novel, minimally invasive method of estimating regional variations in pharyngeal elasticity. Magnetic resonance images for pediatric sleep apnea patients with Down syndrome [9.5 ± 4.3 years (mean age ± standard deviation)] were analyzed to segment airways corresponding to baseline (no mask pressure) and two positive pressures. A three dimensional map was created to evaluate axial and circumferential variation in radial displacements of the airway, dilated by the positive pressures. The displacements were then normalized with respect to the appropriate transmural pressure and radius of an equivalent circle to obtain a measure of airway compliance. The resulting elasticity maps indicated the least and most compliant regions of the pharynx. Airway stiffness of the most compliant region [403 ± 204 (mean ± standard deviation) Pa] decreased with severity of obstructive sleep apnea. The non-linear response of the airway wall to continuous positive airway pressure was patient specific and varied between anatomical locations. We identified two distinct elasticity phenotypes. Patient phenotyping based on airway elasticity can potentially assist clinical practitioners in decision making on the treatments needed to improve airway patency. PMID:26215306

  11. Management of Near-Complete Airway Obstruction Caused by a Vallecular Cyst in an Infant Using a Tongue Tip Traction Suture.

    PubMed

    Wong, Christine M; Ghazal, Elizabeth A; Dyleski, Robin A; Applegate, Richard L

    2016-01-15

    Airway obstruction in infants can be because of a number of airway issues, one of which is a vallecular cyst. Although uncommonly seen, the management strategy for this difficult airway can be applied to many other difficult airway cases. We report the use of a preoperative oral fiberoptic assessment of the airway, use of a tongue stitch, and manipulation of a flexible nasal fiberoptic bronchoscope to secure the airway. Keeping the patient breathing spontaneously with low-dose ketamine also facilitated successful tracheal intubation. PMID:26599736

  12. Toxicity assessment of aggregated/agglomerated cerium oxide nanoparticles in an in vitro 3D airway model: the influence of mucociliary clearance.

    PubMed

    Frieke Kuper, C; Gröllers-Mulderij, Mariska; Maarschalkerweerd, Thérèse; Meulendijks, Nicole M M; Reus, Astrid; van Acker, Frédérique; Zondervan-van den Beuken, Esther K; Wouters, Mariëlle E L; Bijlsma, Sabina; Kooter, Ingeborg M

    2015-03-01

    We investigated the toxicity of aggregated nanoparticles of cerium oxide (CeO2) using an in vitro 3D human bronchial epithelial model that included a mucociliary apparatus (MucilAir™). CeO2 was dispersed in saline and applied to the apical surface of the model. CeO2 did not induce distinct effects in the model, whereas it did in BEAS-2B and A549 cell cultures. The absence of effects of CeO2 was not because of the model's insensitivity. Nanoparticles of zinc oxide (ZnO) elicited positive responses in the toxicological assays. Respiratory mucus (0.1% and 1%) added to dispersions increased aggregation/agglomeration to such an extent that most CeO2 sedimented within a few minutes. Also, the mucociliary apparatus of the model removed CeO2 from the central part of the apical surface to the borders. This 'clearance' may have prevented the majority of CeO2 from reaching the epithelial cells. Chemical analysis of cerium in the basal tissue culture medium showed only minimal translocation of cerium across the 3D barrier. In conclusion, mucociliary defence appeared to prevent CeO2 reaching the respiratory epithelial cells in this 3D in vitro model. This model and approach can be used to study compounds of specific toxicological concern in airway defence mechanisms in vitro. PMID:25448805

  13. Comparative assessment of ProSeal™ laryngeal mask airway intervention versus standard technique of endotracheal extubation for attenuation of pressor response in controlled hypertensive patients

    PubMed Central

    Singh, Raj Pal; Gulabani, Michell; Kaur, Mohandeep; Sood, Rajesh

    2016-01-01

    Background and Aims: Swapping of the endotracheal tube with laryngeal mask airway (LMA) before emergence from anaesthesia is one of the methods employed for attenuation of pressor response at extubation. We decided to compare the placement of ProSeal™ LMA (PLMA) before endotracheal extubation versus conventional endotracheal extubation in controlled hypertensive patients scheduled for elective surgeries under general anaesthesia. Methods: Sixty consenting adult patients were randomly allocated to two groups of thirty each; Group E in whom extubation was performed using standard technique and Group P in whom PLMA was inserted before endotracheal extubation (Bailey manoeuvre). The primary outcome parameter was heart rate (HR). The secondary outcomes were systolic, diastolic and mean blood pressure (MBP), electrocardiogram, oxygen saturation and end-tidal carbon dioxide. Two-tailed paired Student's t-test was used for comparison between the two study groups. The value of P < 0.05 was considered as statistically significant. Results: The patient characteristics, demographic data and surgical procedures were comparable in the two groups. A statistically significant decrease was observed in HR in Group P as compared to Group E. Secondary outcomes such as systolic, diastolic and MBP depicted a statistically insignificant difference. Conclusion: Bailey manoeuvre was not effective method to be completely relied upon during extubation when compared to standard extubation. PMID:27512160

  14. A High-Value, Low-Cost Bubble Continuous Positive Airway Pressure System for Low-Resource Settings: Technical Assessment and Initial Case Reports

    PubMed Central

    Brown, Jocelyn; Machen, Heather; Kawaza, Kondwani; Mwanza, Zondiwe; Iniguez, Suzanne; Lang, Hans; Gest, Alfred; Kennedy, Neil; Miros, Robert; Richards-Kortum, Rebecca; Molyneux, Elizabeth; Oden, Maria

    2013-01-01

    Acute respiratory infections are the leading cause of global child mortality. In the developing world, nasal oxygen therapy is often the only treatment option for babies who are suffering from respiratory distress. Without the added pressure of bubble Continuous Positive Airway Pressure (bCPAP) which helps maintain alveoli open, babies struggle to breathe and can suffer serious complications, and frequently death. A stand-alone bCPAP device can cost $6,000, too expensive for most developing world hospitals. Here, we describe the design and technical evaluation of a new, rugged bCPAP system that can be made in small volume for a cost-of-goods of approximately $350. Moreover, because of its simple design—consumer-grade pumps, medical tubing, and regulators—it requires only the simple replacement of a <$1 diaphragm approximately every 2 years for maintenance. The low-cost bCPAP device delivers pressure and flow equivalent to those of a reference bCPAP system used in the developed world. We describe the initial clinical cases of a child with bronchiolitis and a neonate with respiratory distress who were treated successfully with the new bCPAP device. PMID:23372661

  15. Measuring and imaging small airways dysfunction in asthma

    PubMed Central

    2013-01-01

    Asthma is a chronic inflammatory disorder of the airways causing typical symptoms, and the diagnosis is supported by evidence of airflow obstruction which is variable, reversible or inducible. However, standard assessment of lung function with spirometry does not measure dysfunction in small airways which are < 2 mm in diameter towards the periphery of the lung. These airways make only a small contribution to airway resistance under normal circumstances. Nevertheless, there is mounting evidence that pathology and dysfunction in these small airways are implicated in the pathogenesis and natural history of asthma. Using forced oscillation and the multibreath nitrogen washout techniques, uneven ventilation (ventilation heterogeneity) due to small airways dysfunction has been shown to be an important marker of asthma disease activity, even in the absence of abnormalities in standard spirometric measurements. Recent advances in imaging research, particularly with hyperpolarised gas magnetic resonance imaging, have also given insights into the significance and dynamic nature of ventilation heterogeneity in asthma. The challenge is to integrate these new physiological and imaging insights to further our understanding of asthma and facilitate potential new treatments. PMID:24260727

  16. Chlorine-induced injury to the airways in mice.

    PubMed

    Martin, James G; Campbell, Holly R; Iijima, Hiroaki; Gautrin, Denyse; Malo, Jean-Luc; Eidelman, David H; Hamid, Qutayba; Maghni, Karim

    2003-09-01

    Exposure to chlorine gas (Cl2) causes occupational asthma that we hypothesized occurs through the induction of airway inflammation and airway hyperresponsiveness by oxidative damage. Respiratory mechanics and airway responsiveness to methacholine were assessed in A/J mice 24 hours after a 5-minute exposure to 100, 200, 400, or 800 ppm Cl2 and 2 and 7 days after inhalation of 400 ppm Cl2. Airway responsiveness was higher 24 hours after 400 and 800 ppm Cl2. Responsiveness after inhalation of 400 ppm Cl2 returned to normal by 2 days but was again elevated at 7 days. Airway epithelial loss, patchy alveolar damage, proteinaceous exudates, and inflammatory cells within alveolar walls were observed in animals exposed to 800 ppm Cl2. Macrophages, granulocytes, epithelial cells, and nitrate/nitrite levels increased in lung lavage fluid. Increased inducible nitric oxide synthase expression and oxidation of lung proteins were observed. Epithelial cells and alveolar macrophages from mice exposed to 800 ppm Cl2 stained for 3-nitrotyrosine residues. Inhibition of inducible nitric oxide synthase with 1400W (1 mg/kg) abrogated the Cl2-induced changes in responsiveness. We conclude that chlorine exposure causes functional and pathological changes in the airways associated with oxidative stress. Inducible nitric oxide synthase is involved in the induction of changes in responsiveness to methacholine. PMID:12724121

  17. Obstetric Anaesthetists' Association and Difficult Airway Society guidelines for the management of difficult and failed tracheal intubation in obstetrics*

    PubMed Central

    Mushambi, M C; Kinsella, S M; Popat, M; Swales, H; Ramaswamy, K K; Winton, A L; Quinn, A C

    2015-01-01

    The Obstetric Anaesthetists' Association and Difficult Airway Society have developed the first national obstetric guidelines for the safe management of difficult and failed tracheal intubation during general anaesthesia. They comprise four algorithms and two tables. A master algorithm provides an overview. Algorithm 1 gives a framework on how to optimise a safe general anaesthetic technique in the obstetric patient, and emphasises: planning and multidisciplinary communication; how to prevent the rapid oxygen desaturation seen in pregnant women by advocating nasal oxygenation and mask ventilation immediately after induction; limiting intubation attempts to two; and consideration of early release of cricoid pressure if difficulties are encountered. Algorithm 2 summarises the management after declaring failed tracheal intubation with clear decision points, and encourages early insertion of a (preferably second-generation) supraglottic airway device if appropriate. Algorithm 3 covers the management of the ‘can't intubate, can't oxygenate’ situation and emergency front-of-neck airway access, including the necessity for timely perimortem caesarean section if maternal oxygenation cannot be achieved. Table 1 gives a structure for assessing the individual factors relevant in the decision to awaken or proceed should intubation fail, which include: urgency related to maternal or fetal factors; seniority of the anaesthetist; obesity of the patient; surgical complexity; aspiration risk; potential difficulty with provision of alternative anaesthesia; and post-induction airway device and airway patency. This decision should be considered by the team in advance of performing a general anaesthetic to make a provisional plan should failed intubation occur. The table is also intended to be used as a teaching tool to facilitate discussion and learning regarding the complex nature of decision-making when faced with a failed intubation. Table 2 gives practical considerations of how

  18. Obstetric Anaesthetists' Association and Difficult Airway Society guidelines for the management of difficult and failed tracheal intubation in obstetrics.

    PubMed

    Mushambi, M C; Kinsella, S M; Popat, M; Swales, H; Ramaswamy, K K; Winton, A L; Quinn, A C

    2015-11-01

    The Obstetric Anaesthetists' Association and Difficult Airway Society have developed the first national obstetric guidelines for the safe management of difficult and failed tracheal intubation during general anaesthesia. They comprise four algorithms and two tables. A master algorithm provides an overview. Algorithm 1 gives a framework on how to optimise a safe general anaesthetic technique in the obstetric patient, and emphasises: planning and multidisciplinary communication; how to prevent the rapid oxygen desaturation seen in pregnant women by advocating nasal oxygenation and mask ventilation immediately after induction; limiting intubation attempts to two; and consideration of early release of cricoid pressure if difficulties are encountered. Algorithm 2 summarises the management after declaring failed tracheal intubation with clear decision points, and encourages early insertion of a (preferably second-generation) supraglottic airway device if appropriate. Algorithm 3 covers the management of the 'can't intubate, can't oxygenate' situation and emergency front-of-neck airway access, including the necessity for timely perimortem caesarean section if maternal oxygenation cannot be achieved. Table 1 gives a structure for assessing the individual factors relevant in the decision to awaken or proceed should intubation fail, which include: urgency related to maternal or fetal factors; seniority of the anaesthetist; obesity of the patient; surgical complexity; aspiration risk; potential difficulty with provision of alternative anaesthesia; and post-induction airway device and airway patency. This decision should be considered by the team in advance of performing a general anaesthetic to make a provisional plan should failed intubation occur. The table is also intended to be used as a teaching tool to facilitate discussion and learning regarding the complex nature of decision-making when faced with a failed intubation. Table 2 gives practical considerations of how to

  19. Assessing vulnerability to drought: identifying underlying factors across Europe

    NASA Astrophysics Data System (ADS)

    Urquijo, Julia; Gonzalez Tánago, Itziar; Ballesteros, Mario; De Stefano, Lucia

    2015-04-01

    Drought is considered one of the most severe and damaging natural hazards in terms of people and sectors affected and associated losses. Drought is a normal and recurrent climatic phenomenon that occurs worldwide, although its spatial and temporal characteristics vary significantly among climates. In the case of Europe, in the last thirty years, the region has suffered several drought events that have caused estimated economic damages over a €100 billion and have affected almost 20% of its territory and population. In recent years, there has been a growing awareness among experts and authorities of the need to shift from a reactive crisis approach to a drought risk management approach, as well as of the importance of designing and implementing policies, strategies and plans at country and river basin levels to deal with drought. The identification of whom and what is vulnerable to drought is a central aspect of drought risk mitigation and planning and several authors agree that societal vulnerability often determines drought risk more than the actual precipitation shortfalls. The final aim of a drought vulnerability assessment is to identify the underlying sources of drought impact, in order to develop policy options that help to enhance coping capacity and therefore to prevent drought impact. This study identifies and maps factors underlying vulnerability to drought across Europe. The identification of factors influencing vulnerability starts from the analysis of past drought impacts in four European socioeconomic sectors. This analysis, along with an extensive literature review, led to the selection of vulnerability factors that are both relevant and adequate for the European context. Adopting the IPCC model, vulnerability factors were grouped to describe exposure, sensitivity and adaptive capacity. The aggregation of these components has resulted in the mapping of vulnerability to drought across Europe at NUTS02 level. Final results have been compared with

  20. A real-time assessment of factors influencing medication events.

    PubMed

    Dollarhide, Adrian W; Rutledge, Thomas; Weinger, Matthew B; Fisher, Erin Stucky; Jain, Sonia; Wolfson, Tanya; Dresselhaus, Timothy R

    2014-01-01

    Reducing medical error is critical to improving the safety and quality of healthcare. Physician stress, fatigue, and excessive workload are performance-shaping factors (PSFs) that may influence medical events (actual administration errors and near misses), but direct relationships between these factors and patient safety have not been clearly defined. This study assessed the real-time influence of emotional stress, workload, and sleep deprivation on self-reported medication events by physicians in academic hospitals. During an 18-month study period, 185 physician participants working at four university-affiliated teaching hospitals reported medication events using a confidential reporting application on handheld computers. Emotional stress scores, perceived workload, patient case volume, clinical experience, total sleep, and demographic variables were also captured via the handheld computers. Medication event reports (n = 11) were then correlated with these demographic and PSFs. Medication events were associated with 36.1% higher perceived workload (p < .05), 38.6% higher inpatient caseloads (p < .01), and 55.9% higher emotional stress scores (p < .01). There was a trend for reported events to also be associated with less sleep (p = .10). These results confirm the effect of factors influencing medication events, and support attention to both provider and hospital environmental characteristics for improving patient safety. PMID:23551380

  1. Assessing peridomestic entomological factors as predictors for Lyme disease

    USGS Publications Warehouse

    Connally, N.P.; Ginsberg, H.S.; Mather, T.N.

    2006-01-01

    The roles of entomologic risk factors, including density of nymphal blacklegged ticks (Ixodes scapularis), prevalence of nymphal infection with the etiologic agent (Borrelia burgdorferi), and density of infected nymphs, in determining the risk of human Lyme disease were assessed at residences in the endemic community of South Kingstown, RI. Nymphs were sampled between May and July from the wooded edge around 51 and 47 residential properties in 2002 and 2003, respectively. Nymphs were collected from all residences sampled. Tick densities, infection rates, and densities of infected nymphs were all significantly higher around homes reporting Lyme disease histories in 2003, while only infection rates were significantly higher in 2002. However, densities of infected nymphs did not significantly predict the probability of Lyme disease at a residence (by logistic regression) in either year. There were no significant differences in entomologic risk factors between homes with state-confirmed Lyme disease histories and homes with self-reported cases (not reported to the state health department). Therefore, although entomologic risk factors tended to be higher at residences with cases of Lyme disease, entomological indices, in the absence of human behavior measures, were not useful predictors of Lyme disease at the scale of individual residences in a tick-endemic community.

  2. [Clinical relevance of distal airway involvement in asthma].

    PubMed

    Torrego Fernández, Alfons; Muñoz Cano, Rosa M

    2011-04-01

    Asthma continues to be a global health problem, despite advances in diagnostic techniques and treatment. The inflammatory nature of asthma is currently indisputable, as is the involvement of the entire respiratory tree, both the proximal and most distal airways, which has been demonstrated in multiple studies. The development of the therapeutic arsenal, with more potent drugs and improved inhalation devices, has allowed a certain control to be maintained over the inflammatory process, although the inability to reach the most distal points of the airways has posed a stumbling block that seems difficult to overcome. However, the available information on the real role of distal airway involvement in asthma remains very scarce. Physiopathological evidence shows that, in addition to the large airways, the small or distal airways (those with a diameter of less than 2 mm) substantially contribute to the severity of asthma. Several studies have shown that the inflammatory process seems to be more intense in this area. This finding has been related to nocturnal asthma and an increase in glucocorticoid receptor-beta-expressing cells, associated with corticosteroid-resistant asthma and fatal asthma. Equally, small airway involvement seems to be a highly important factor in asthma in the pediatric age group. PMID:21640280

  3. Maxillofacial Injury-Not Always a Difficult Airway.

    PubMed

    Glasheen, John; Hennelly, David; Cusack, Stephen

    2015-08-01

    The optimal method for securing the airway in injured patients is controversial. Maxillofacial injury has been shown to be a marker for difficult airway management; however, a delay in intubation may result in deterioration of intubating conditions due to further airway bleeding and swelling. Decisions on the timing and method of airway management depend on multiple factors, including patient characteristics, the skill set of the clinicians, and logistical considerations. This report describes the case of a multi-agency response to a motor-vehicle collision in a rural area in Ireland. One young male patient had sustained significant maxillofacial injuries, multiple limb injuries, and had a decreased level of consciousness. Further airway compromise occurred following extrication. Difficult intubation was predicted; however, abnormal jaw mobility from bilateral mandibular fractures enabled easy laryngoscopy and intubation. Although preparation must be made for difficult airway management in the setting of maxillofacial injury, appropriately trained and experienced practitioners should not be deterred from performing early intubation when indicated. PMID:25994879

  4. Airway hyperresponsiveness; smooth muscle as the principal actor

    PubMed Central

    Lauzon, Anne-Marie; Martin, James G.

    2016-01-01

    Airway hyperresponsiveness (AHR) is a defining characteristic of asthma that refers to the capacity of the airways to undergo exaggerated narrowing in response to stimuli that do not result in comparable degrees of airway narrowing in healthy subjects. Airway smooth muscle (ASM) contraction mediates airway narrowing, but it remains uncertain as to whether the smooth muscle is intrinsically altered in asthmatic subjects or is responding abnormally as a result of the milieu in which it sits. ASM in the trachea or major bronchi does not differ in its contractile characteristics in asthmatics, but the more pertinent peripheral airways await complete exploration. The mass of ASM is increased in many but not all asthmatics and therefore cannot be a unifying hypothesis for AHR, although when increased in mass it may contribute to AHR. The inability of a deep breath to reverse or prevent bronchial narrowing in asthma may reflect an intrinsic difference in the mechanisms that lead to softening of contracted ASM when subjected to stretch. Cytokines such as interleukin-13 and tumor necrosis factor-α promote a more contractile ASM phenotype. The composition and increased stiffness of the matrix in which ASM is embedded promotes a more proliferative and pro-inflammatory ASM phenotype, but the expected dedifferentiation and loss of contractility have not been shown. Airway epithelium may drive ASM proliferation and/or molecular remodeling in ways that may lead to AHR. In conclusion, AHR is likely multifactorial in origin, reflecting the plasticity of ASM properties in the inflammatory environment of the asthmatic airway. PMID:26998246

  5. Airway hyperresponsiveness; smooth muscle as the principal actor.

    PubMed

    Lauzon, Anne-Marie; Martin, James G

    2016-01-01

    Airway hyperresponsiveness (AHR) is a defining characteristic of asthma that refers to the capacity of the airways to undergo exaggerated narrowing in response to stimuli that do not result in comparable degrees of airway narrowing in healthy subjects. Airway smooth muscle (ASM) contraction mediates airway narrowing, but it remains uncertain as to whether the smooth muscle is intrinsically altered in asthmatic subjects or is responding abnormally as a result of the milieu in which it sits. ASM in the trachea or major bronchi does not differ in its contractile characteristics in asthmatics, but the more pertinent peripheral airways await complete exploration. The mass of ASM is increased in many but not all asthmatics and therefore cannot be a unifying hypothesis for AHR, although when increased in mass it may contribute to AHR. The inability of a deep breath to reverse or prevent bronchial narrowing in asthma may reflect an intrinsic difference in the mechanisms that lead to softening of contracted ASM when subjected to stretch. Cytokines such as interleukin-13 and tumor necrosis factor-α promote a more contractile ASM phenotype. The composition and increased stiffness of the matrix in which ASM is embedded promotes a more proliferative and pro-inflammatory ASM phenotype, but the expected dedifferentiation and loss of contractility have not been shown. Airway epithelium may drive ASM proliferation and/or molecular remodeling in ways that may lead to AHR. In conclusion, AHR is likely multifactorial in origin, reflecting the plasticity of ASM properties in the inflammatory environment of the asthmatic airway. PMID:26998246

  6. Airway cooling and mucosal injury during cold weather exercise.

    PubMed

    Davis, M S; Lockard, A J; Marlin, D J; Freed, A N

    2002-09-01

    In human subjects that exercise strenuously in cold weather, there is evidence that hyperventilation with cold air leads to peripheral airway cooling, desiccation and mucosal injury. Our hypothesis was that hyperventilation with cold air can result in penetration of unconditioned air (air that is not completely warmed and humidified) into the peripheral airways of exercising horses, resulting in peripheral airway mucosal injury. To test this hypothesis, a thermister-tipped catheter was inserted through the midcervical trachea and advanced into a sublobar bronchus in three horses that cantered on a treadmill at 6.6 m/s while breathing cold (5 degrees C) air. The mean (+/- s.e.) intra-airway temperature during cantering was 33.3 +/- 0.4 degrees C, a value comparable to the bronchial lumen temperatures measured in man during maximal exercise while breathing subfreezing dry air. In a second experiment, 6 fit Thoroughbred racehorses with satisfactory performance were used to determine whether strenuous exercise in cold conditions can produce airway injury. Horses were assigned to Exercise (E) or Control (C) groups in a random crossover design. Samples of bronchoalveolar lavage fluid (BALF) in the E treatment were recovered within 30 min of galloping exercise in 4 degrees C, 100% relative humidity (E), while in C BALF samples were obtained when the horses had not performed any exercise for at least 48 h prior. Ciliated epithelial cells in BALF were higher in E than in the C treatment. Similar results have been found in human athletes and laboratory animal models of cold weather exercise. These results support the hypothesis that, similar to man, horses that exercise in cold weather experience peripheral airway mucosal injury due to the penetration of unconditioned air. Furthermore, these results suggest that airway cooling and desiccation may be a factor in airway inflammation commonly found in equine athletes. PMID:12405726

  7. Putting the Squeeze on Airway Epithelia.

    PubMed

    Park, Jin-Ah; Fredberg, Jeffrey J; Drazen, Jeffrey M

    2015-07-01

    Asthma is characterized by chronic inflammation, airway hyperresponsiveness, and progressive airway remodeling. The airway epithelium is known to play a critical role in the initiation and perpetuation of these processes. Here, we review how excessive epithelial stress generated by bronchoconstriction is sufficient to induce airway remodeling, even in the absence of inflammatory cells. PMID:26136543

  8. Putting the Squeeze on Airway Epithelia

    PubMed Central

    Park, Jin-Ah; Fredberg, Jeffrey J.

    2015-01-01

    Asthma is characterized by chronic inflammation, airway hyperresponsiveness, and progressive airway remodeling. The airway epithelium is known to play a critical role in the initiation and perpetuation of these processes. Here, we review how excessive epithelial stress generated by bronchoconstriction is sufficient to induce airway remodeling, even in the absence of inflammatory cells. PMID:26136543

  9. Methacholine-Induced Variations in Airway Volume and the Slope of the Alveolar Capnogram Are Distinctly Associated with Airflow Limitation and Airway Closure

    PubMed Central

    Plantier, Laurent; Marchand-Adam, Sylvain; Boyer, Laurent; Taillé, Camille; Delclaux, Christophe

    2015-01-01

    Mechanisms driving alteration of lung function in response to inhalation of a methacholine aerosol are incompletely understood. To explore to what extent large and small airways contribute to airflow limitation and airway closure in this context, volumetric capnography was performed before (n = 93) and after (n = 78) methacholine provocation in subjects with an intermediate clinical probability of asthma. Anatomical dead space (VDaw), reflecting large airway volume, and the slope of the alveolar capnogram (slope3), an index of ventilation heterogeneity linked to small airway dysfunction, were determined. At baseline, VDaw was positively correlated with lung volumes, FEV1 and peak expiratory flow, while slope3 was not correlated with any lung function index. Variations in VDaw and slope3 following methacholine stimulation were correlated to a small degree (R2 = -0.20). Multivariate regression analysis identified independent associations between variation in FEV1 and variations in both VDaw (Standardized Coefficient-SC = 0.66) and Slope3 (SC = 0.35). By contrast, variation in FVC was strongly associated with variations in VDaw (SC = 0.8) but not Slope3. Thus, alterations in the geometry and/or function of large and small airways were weakly correlated and contributed distinctly to airflow limitation. While both large and small airways contributed to airflow limitation as assessed by FEV1, airway closure as assessed by FVC reduction mostly involved the large airways. PMID:26599006

  10. Methacholine-Induced Variations in Airway Volume and the Slope of the Alveolar Capnogram Are Distinctly Associated with Airflow Limitation and Airway Closure.

    PubMed

    Plantier, Laurent; Marchand-Adam, Sylvain; Boyer, Laurent; Taillé, Camille; Delclaux, Christophe

    2015-01-01

    Mechanisms driving alteration of lung function in response to inhalation of a methacholine aerosol are incompletely understood. To explore to what extent large and small airways contribute to airflow limitation and airway closure in this context, volumetric capnography was performed before (n = 93) and after (n = 78) methacholine provocation in subjects with an intermediate clinical probability of asthma. Anatomical dead space (VDaw), reflecting large airway volume, and the slope of the alveolar capnogram (slope3), an index of ventilation heterogeneity linked to small airway dysfunction, were determined. At baseline, VDaw was positively correlated with lung volumes, FEV1 and peak expiratory flow, while slope3 was not correlated with any lung function index. Variations in VDaw and slope3 following methacholine stimulation were correlated to a small degree (R2 = -0.20). Multivariate regression analysis identified independent associations between variation in FEV1 and variations in both VDaw (Standardized Coefficient-SC = 0.66) and Slope3 (SC = 0.35). By contrast, variation in FVC was strongly associated with variations in VDaw (SC = 0.8) but not Slope3. Thus, alterations in the geometry and/or function of large and small airways were weakly correlated and contributed distinctly to airflow limitation. While both large and small airways contributed to airflow limitation as assessed by FEV1, airway closure as assessed by FVC reduction mostly involved the large airways. PMID:26599006

  11. Residual Daytime Sleepiness in Obstructive Sleep Apnea After Continuous Positive Airway Pressure Optimization: Causes and Management.

    PubMed

    Chapman, Julia L; Serinel, Yasmina; Marshall, Nathaniel S; Grunstein, Ronald R

    2016-09-01

    Excessive daytime sleepiness (EDS) is common in obstructive sleep apnea (OSA), but it is also common in the general population. When sleepiness remains after continuous positive airway pressure (CPAP) treatment of OSA, comorbid conditions or permanent brain injury before CPAP therapy may be the cause of the residual sleepiness. There is currently no broad approach to treating residual EDS in patients with OSA. Individual assessment must be made of comorbid conditions and medications, and of lifestyle factors that may be contributing to the sleepiness. Modafinil and armodafinil are the only pharmacologic agents indicated for residual sleepiness in these patients. PMID:27542881

  12. Characterisation factors for life cycle impact assessment of sound emissions.

    PubMed

    Cucurachi, S; Heijungs, R

    2014-01-15

    Noise is a serious stressor affecting the health of millions of citizens. It has been suggested that disturbance by noise is responsible for a substantial part of the damage to human health. However, no recommended approach to address noise impacts was proposed by the handbook for life cycle assessment (LCA) of the European Commission, nor are characterisation factors (CFs) and appropriate inventory data available in commonly used databases. This contribution provides CFs to allow for the quantification of noise impacts on human health in the LCA framework. Noise propagation standards and international reports on acoustics and noise impacts were used to define the model parameters. Spatial data was used to calculate spatially-defined CFs in the form of 10-by-10-km maps. The results of this analysis were combined with data from the literature to select input data for representative archetypal situations of emission (e.g. urban day with a frequency of 63 Hz, rural night at 8000 Hz, etc.). A total of 32 spatial and 216 archetypal CFs were produced to evaluate noise impacts at a European level (i.e. EU27). The possibility of a user-defined characterisation factor was added to support the possibility of portraying the situation of full availability of information, as well as a highly-localised impact analysis. A Monte Carlo-based quantitative global sensitivity analysis method was applied to evaluate the importance of the input factors in determining the variance of the output. The factors produced are ready to be implemented in the available LCA databases and software. The spatial approach and archetypal approach may be combined and selected according to the amount of information available and the life cycle under study. The framework proposed and used for calculations is flexible enough to be expanded to account for impacts on target subjects other than humans and to continents other than Europe. PMID:24035845

  13. KGF alters gene expression in human airway epithelia: potential regulation of the inflammatory response.

    PubMed

    Prince, L S; Karp, P H; Moninger, T O; Welsh, M J

    2001-07-17

    Keratinocyte growth factor (KGF) regulates several functions in adult and developing lung epithelia; it causes proliferation, stimulates secretion of fluid and electrolytes, enhances repair, and may minimize injury. To gain insight into the molecular processes influenced by KGF, we applied KGF to primary cultures of well-differentiated human airway epithelia and used microarray hybridization to assess the abundance of gene transcripts. Of 7,069 genes tested, KGF changed expression levels of 910. Earlier studies showed that KGF causes epithelial proliferation, and as expected, treatment altered expression of numerous genes involved in cell proliferation. We found that KGF stimulated transepithelial Cl(-) transport, but the number of cystic fibrosis (CF) transmembrane conductance regulator (CFTR) transcripts fell. Although transcripts for ClC-1 and ClC-7 Cl(-) channels increased, KGF failed to augment transepithelial Cl(-) transport in CF epithelia, suggesting that KGF-stimulated Cl(-) transport in differentiated airway epithelia depends on the CFTR Cl(-) channel. Interestingly, KGF decreased transcripts for many interferon (IFN)-induced genes. IFN causes trafficking of Stat dimers to the nucleus, where they activate transcription of IFN-induced genes. We found that KGF prevented the IFN-stimulated trafficking of Stat1 from the cytosol to the nucleus, suggesting a molecular mechanism for KGF-mediated suppression of the IFN-signaling pathway. These results suggest that in addition to stimulating proliferation and repair of damaged airway epithelia, KGF stimulates Cl(-) transport and may dampen the response of epithelial cells to inflammatory mediators. PMID:11459923

  14. Chronic exposure to perfluorinated compounds: Impact on airway hyperresponsiveness and inflammation

    PubMed Central

    Ryu, Min H.; Jha, Aruni; Ojo, Oluwaseun O.; Mahood, Thomas H.; Basu, Sujata; Detillieux, Karen A.; Nikoobakht, Neda; Wong, Charles S.; Loewen, Mark; Becker, Allan B.

    2014-01-01

    Emerging epidemiological evidence reveals a link between lung disease and exposure to indoor pollutants such as perfluorinated compounds (PFCs). PFC exposure during critical developmental stages may increase asthma susceptibility. Thus, in a murine model, we tested the hypothesis that early life and continued exposure to two ubiquitous household PFCs, perfluorooctanoic acid (PFOA) and perflurooctanesulfonic acid (PFOS), can induce lung dysfunction that exacerbates allergen-induced airway hyperresponsiveness (AHR) and inflammation. Balb/c mice were exposed to PFOA or PFOS (4 mg/kg chow) from gestation day 2 to 12 wk of age by feeding pregnant and nursing dams, and weaned pups. Some pups were also sensitized and challenged with ovalbumin (OVA). We assessed lung function and inflammatory cell and cytokine expression in the lung and examined bronchial goblet cell number. PFOA, but not PFOS, without the OVA sensitization/challenge induced AHR concomitant with a 25-fold increase of lung macrophages. PFOA exposure did not affect OVA-induced lung inflammatory cell number. In contrast, PFOS exposure inhibited OVA-induced lung inflammation, decreasing total cell number in lung lavage by 68.7%. Interferon-γ mRNA in the lung was elevated in all PFC-exposed groups. Despite these effects, neither PFOA nor PFOS affected OVA-induced AHR. Our data do not reveal PFOA or PFOS exposure as a risk factor for more severe allergic asthma-like symptoms, but PFOA alone can induce airway inflammation and alter airway function. PMID:25217661

  15. Increased airway glucose increases airway bacterial load in hyperglycaemia

    PubMed Central

    Gill, Simren K.; Hui, Kailyn; Farne, Hugo; Garnett, James P.; Baines, Deborah L.; Moore, Luke S.P.; Holmes, Alison H.; Filloux, Alain; Tregoning, John S.

    2016-01-01

    Diabetes is associated with increased frequency of hospitalization due to bacterial lung infection. We hypothesize that increased airway glucose caused by hyperglycaemia leads to increased bacterial loads. In critical care patients, we observed that respiratory tract bacterial colonisation is significantly more likely when blood glucose is high. We engineered mutants in genes affecting glucose uptake and metabolism (oprB, gltK, gtrS and glk) in Pseudomonas aeruginosa, strain PAO1. These mutants displayed attenuated growth in minimal medium supplemented with glucose as the sole carbon source. The effect of glucose on growth in vivo was tested using streptozocin-induced, hyperglycaemic mice, which have significantly greater airway glucose. Bacterial burden in hyperglycaemic animals was greater than control animals when infected with wild type but not mutant PAO1. Metformin pre-treatment of hyperglycaemic animals reduced both airway glucose and bacterial load. These data support airway glucose as a critical determinant of increased bacterial load during diabetes. PMID:27273266

  16. Increased airway glucose increases airway bacterial load in hyperglycaemia.

    PubMed

    Gill, Simren K; Hui, Kailyn; Farne, Hugo; Garnett, James P; Baines, Deborah L; Moore, Luke S P; Holmes, Alison H; Filloux, Alain; Tregoning, John S

    2016-01-01

    Diabetes is associated with increased frequency of hospitalization due to bacterial lung infection. We hypothesize that increased airway glucose caused by hyperglycaemia leads to increased bacterial loads. In critical care patients, we observed that respiratory tract bacterial colonisation is significantly more likely when blood glucose is high. We engineered mutants in genes affecting glucose uptake and metabolism (oprB, gltK, gtrS and glk) in Pseudomonas aeruginosa, strain PAO1. These mutants displayed attenuated growth in minimal medium supplemented with glucose as the sole carbon source. The effect of glucose on growth in vivo was tested using streptozocin-induced, hyperglycaemic mice, which have significantly greater airway glucose. Bacterial burden in hyperglycaemic animals was greater than control animals when infected with wild type but not mutant PAO1. Metformin pre-treatment of hyperglycaemic animals reduced both airway glucose and bacterial load. These data support airway glucose as a critical determinant of increased bacterial load during diabetes. PMID:27273266

  17. Rare Upper Airway Anomalies.

    PubMed

    Windsor, Alanna; Clemmens, Clarice; Jacobs, Ian N

    2016-01-01

    A broad spectrum of congenital upper airway anomalies can occur as a result of errors during embryologic development. In this review, we will describe the clinical presentation, diagnosis, and management strategies for a few select, rare congenital malformations of this system. The diagnostic tools used in workup of these disorders range from prenatal tests to radiological imaging, swallowing evaluations, indirect or direct laryngoscopy, and rigid bronchoscopy. While these congenital defects can occur in isolation, they are often associated with disorders of other organ systems or may present as part of a syndrome. Therefore workup and treatment planning for patients with these disorders often involves a team of multiple specialists, including paediatricians, otolaryngologists, pulmonologists, speech pathologists, gastroenterologists, and geneticists. PMID:26277452

  18. [Reactive airways dysfunction syndrome].

    PubMed

    Costa, R; Orriols, R

    2005-01-01

    Reactive airways dysfunction syndrome, better known as RADS, was described as a clinical entity consisting in the appearance of bronchial asthma due to massive toxic inhalation. The term was coined and recognised for the first time in 1985. Since then different publications have verified new cases as well as different causal agents. It usually arises from an accident at the work place and in closed or poorly ventilated spaces, where high concentrations of irritant products are inhaled in the form of gas, smoke or vapour. In the following minutes or hours symptoms of bronchial obstruction appear in an acute form, with bronchial hyperresponsiveness persisting for months or years. The affected patients do not show a recurrence of symptoms following exposure to non-toxic doses of the same agent that started the symptoms. This is why diagnosis is based on clinical manifestations as it is not reproducible through a provocation test. PMID:15915173

  19. Lentiviral vector gene transfer to porcine airways.

    PubMed

    Sinn, Patrick L; Cooney, Ashley L; Oakland, Mayumi; Dylla, Douglas E; Wallen, Tanner J; Pezzulo, Alejandro A; Chang, Eugene H; McCray, Paul B

    2012-01-01

    In this study, we investigated lentiviral vector development and transduction efficiencies in well-differentiated primary cultures of pig airway epithelia (PAE) and wild-type pigs in vivo. We noted gene transfer efficiencies similar to that observed for human airway epithelia (HAE). Interestingly, feline immunodeficiency virus (FIV)-based vectors transduced immortalized pig cells as well as pig primary cells more efficiently than HIV-1-based vectors. PAE express TRIM5α, a well-characterized species-specific lentiviral restriction factor. We contrasted the restrictive properties of porcine TRIM5α against FIV- and HIV-based vectors using gain and loss of function approaches. We observed no effect on HIV-1 or FIV conferred transgene expression in response to porcine TRIM5α overexpression or knockdown. To evaluate the ability of GP64-FIV to transduce porcine airways in vivo, we delivered vector expressing mCherry to the tracheal lobe of the lung and the ethmoid sinus of 4-week-old pigs. One week later, epithelial cells expressing mCherry were readily detected. Our findings indicate that pseudotyped FIV vectors confer similar tropisms in porcine epithelia as observed in human HAE and provide further support for the selection of GP64 as an appropriate envelope pseudotype for future preclinical gene therapy studies in the porcine model of cystic fibrosis (CF).Molecular Therapy - Nucleic Acids (2012) 1, e56; doi:10.1038/mtna.2012.47; published online 27 November 2012. PMID:23187455

  20. Human factors assessments of D and D technologies

    SciTech Connect

    Carpenter, C.P.; Evans, T.T.; McCabe, B.

    2000-07-01

    On April 2, 1997, the US Secretary of Energy directed the US Assistant Secretary of Environmental Management and of Safety and Health to require field input of appropriate data to ensure that safety and health considerations were properly addressed in the Accelerating Cleanup: Focus on 2006 Plan. The US Department of Energy (DOE) field managers have committed to the Secretary that they will fully implement integrated safety management systems (ISMSs) at their respective sites by the end of fiscal year 1999. The Secretary has further directed that headquarters safety and health guidance be developed to support consistent and comprehensive project baseline summaries from the field. The Secretary has committed to institutionalizing ISMS as an integral component of the way the DOE conducts its business. The Defense Nuclear Facilities Safety Board continues to oversee and closely monitor the DOE's commitment to the safety and health of its workers. The DOE is committed to a management system approach to ensure that work is performed in a manner that protects the worker, public, and environment. The Deactivation and Decommissioning Focus Area (DDFA) is actively addressing the need to incorporate environmental safety and health (ES and H) considerations in developing technologies. The DDFA is partnered with the Operating Engineers National Hazmat Program (OENHP) to evaluate the ES and H considerations of the innovative and improved decontamination and decommissioning technologies. Part of the implementation of the ES and H work practices in the field is through a cooperative agreement between the National Energy Technology Laboratory (NETL) and the OENHP. The objective of this program is to establish an International Environmental Technology and Training Center to conduct human factors assessments and protocols on environmental technologies. The intent of the human factors assessments is to enhance the effectiveness and efficiency of the technologies and to enhance

  1. Epithelial injury and repair in airways diseases.

    PubMed

    Grainge, Christopher L; Davies, Donna E

    2013-12-01

    Asthma is a common chronic disease characterized by variable respiratory distress with underlying airway inflammation and airflow obstruction. The incidence of asthma has risen inexorably over the past 50 years, suggesting that environmental factors are important in its etiology. All inhaled environmental stimuli interact with the lung at the respiratory epithelium, and it is a testament to the effectiveness of the airway innate defenses that the majority of inhaled substances are cleared without the need to elicit an inflammatory response. However, once this barrier is breached, effective communication with immune and inflammatory cells is required to protect the internal milieu of the lung. In asthma, the respiratory epithelium is known to be structurally and functionally abnormal. Structurally, the epithelium shows evidence of damage and has more mucus-producing cells than normal airways. Functionally, the airway epithelial barrier can be more permeable and more sensitive to oxidants and show a deficient innate immune response to respiratory virus infection compared with that in normal individuals. The potential of a susceptible epithelium and the underlying mesenchyme to create a microenvironment that enables deviation of immune and inflammatory responses to external stimuli may be crucial in the development and progression of asthma. In this review, we consider three important groups of environmental stimuli on the epithelium in asthma: oxidants, such as environmental pollution and acetaminophen; viruses, including rhinovirus; and agents that cause barrier disruption, such as house dust mite allergens. The pathology associated with each stimulus is considered, and potential future treatments arising from research on their effects are presented. PMID:24297122

  2. Divers' lung function: small airways disease?

    PubMed Central

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

    1990-01-01

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

  3. Assessment of Risk Factors in Patients With Myocardial Infarction

    PubMed Central

    Kiani, Fatemeh; Hesabi, Nasrin; Arbabisarjou, Azizollah

    2016-01-01

    Background: Coronary artery diseases (CAD) are one of the important health problems in the world, although considerable progresses have been made to decrease the mortality, they are still the first cause of death in many countries. Hence, the necessity of examining effective factors and risk factors on CAD can be one of the most important health priorities in many countries like Iran. Objective: This study was performed to assess the risk factors in patients with myocardial infarction (MI) in Zahedan. Materials and Methods: This is a cross sectional study in which 213 patients were examined. They had been diagnosed to have heart failure. Data gathering took 18 months. Data gathering tool was a designed checklist which was filled up by an experienced nurse during interview. Obtained results were recorded in files and analyzed in SPSS 21. Results: Results showed that 70% of patients were women and only 30% were men. 48% of them were illiterate and patients mean age was 58.3. SD had been 12.6. The mean of pain onset time till referring to hospital was 11 hours with SD of 2.1. 17% of patients (coronary artery diseases history), 25.5% (hypertension history), 26% (diabetes history), 15.5% (cholesterol history), 13% (smoking) and 3% have reported CABG history. The majority of people who referred had inferior MI (40.4%). 67.1% normal rhythm, 2.8% atrial fibrillation and 16% had ventricular tachycardia. Statistical tests showed a significant correlation between sex and the mean of referring time (p<0.05) but the relation between age and referring time was not significant. Conclusion: Effective risk factors on MI were recognized in this study. Some of them such as age, sex and education cannot be modified but many are controllable such as hypertension, diabetes, cholesterol, and smoking and on time referring after pain onset. Having considered the results of this study health promotion for society and especially vulnerable people can be provided by omitting or reducing risk

  4. Apoptosis and the Airway Epithelium

    PubMed Central

    White, Steven R.

    2011-01-01

    The airway epithelium functions as a barrier and front line of host defense in the lung. Apoptosis or programmed cell death can be elicited in the epithelium as a response to viral infection, exposure to allergen or to environmental toxins, or to drugs. While apoptosis can be induced via activation of death receptors on the cell surface or by disruption of mitochondrial polarity, epithelial cells compared to inflammatory cells are more resistant to apoptotic stimuli. This paper focuses on the response of airway epithelium to apoptosis in the normal state, apoptosis as a potential regulator of the number and types of epithelial cells in the airway, and the contribution of epithelial cell apoptosis in important airways diseases. PMID:22203854

  5. Extraglottic airway devices: A review

    PubMed Central

    Ramaiah, Ramesh; Das, Debasmita; Bhananker, Sanjay M; Joffe, Aaron M

    2014-01-01

    Extraglottic airway devices (EAD) have become an integral part of anesthetic care since their introduction into clinical practice 25 years ago and have been used safely hundreds of millions of times, worldwide. They are an important first option for difficult ventilation during both in-hospital and out-of-hospital difficult airway management and can be utilized as a conduit for tracheal intubation either blindly or assisted by another technology (fiberoptic endoscopy, lightwand). Thus, the EAD may be the most versatile single airway technique in the airway management toolbox. However, despite their utility, knowledge regarding specific devices and the supporting data for their use is of paramount importance to patient's safety. In this review, number of commercially available EADs are discussed and the reported benefits and potential pitfalls are highlighted. PMID:24741502

  6. United airway disease: current perspectives

    PubMed Central

    Giavina-Bianchi, Pedro; Aun, Marcelo Vivolo; Takejima, Priscila; Kalil, Jorge; Agondi, Rosana Câmara

    2016-01-01

    Upper and lower airways are considered a unified morphological and functional unit, and the connection existing between them has been observed for many years, both in health and in disease. There is strong epidemiologic, pathophysiologic, and clinical evidence supporting an integrated view of rhinitis and asthma: united airway disease in the present review. The term “united airway disease” is opportune, because rhinitis and asthma are chronic inflammatory diseases of the upper and lower airways, which can be induced by allergic or nonallergic reproducible mechanisms, and present several phenotypes. Management of rhinitis and asthma must be jointly carried out, leading to better control of both diseases, and the lessons of the Allergic Rhinitis and Its Impact on Asthma initiative cannot be forgotten. PMID:27257389

  7. Tachykinin receptors and airway pathophysiology.

    PubMed

    Maggi, C A

    1993-05-01

    The mammalian tachykinins (TKs), substance P and neurokinin A, are present in sensory nerve fibres in the upper and lower airways of various mammalian species, including humans. TKs are released from these afferent nerves in an "efferent" mode at peripheral level, especially in response to irritant stimuli. TKs exert a variety of biological effects (bronchoconstriction, plasma protein extravasation, stimulation of mucus secretion), collectively known as "neurogenic inflammation", and this process is thought to be of potential pathogenic relevance for various airway diseases. The recent development of potent and selective TK receptor antagonists on the one hand provides important new tools for the understanding of basic airway physiology and pathophysiology and, on the other, opens new possibilities for therapy of airway diseases. PMID:8390944

  8. Imaging of the Distal Airways

    PubMed Central

    Tashkin, Donald P.; de Lange, Eduard E.

    2009-01-01

    Imaging techniques of the lung continues to advance with improving ability to image the more distal airways. Two imaging techniques are reviewed, computerized tomography and magnetic resonance with hyperpolarized helium-3. PMID:19962040

  9. The Virtual Pediatric Airways Workbench.

    PubMed

    Quammen, Cory W; Taylor Ii, Russell M; Krajcevski, Pavel; Mitran, Sorin; Enquobahrie, Andinet; Superfine, Richard; Davis, Brad; Davis, Stephanie; Zdanski, Carlton

    2016-01-01

    The Virtual Pediatric Airways Workbench (VPAW) is a patient-centered surgical planning software system targeted to pediatric patients with airway obstruction. VPAW provides an intuitive surgical planning interface for clinicians and supports quantitative analysis regarding prospective surgeries to aid clinicians deciding on potential surgical intervention. VPAW enables a full surgical planning pipeline, including importing DICOM images, segmenting the airway, interactive 3D editing of airway geometries to express potential surgical treatment planning options, and creating input files for offline geometric analysis and computational fluid dynamics simulations for evaluation of surgical outcomes. In this paper, we describe the VPAW system and its use in one case study with a clinician to successfully describe an intended surgery outcome. PMID:27046595

  10. Role of Rho kinase isoforms in murine allergic airway responses.

    PubMed

    Zhu, M; Liu, P-Y; Kasahara, D I; Williams, A S; Verbout, N G; Halayko, A J; Fedulov, A; Shoji, T; Williams, E S; Noma, K; Shore, S A; Liao, J K

    2011-10-01

    Inhibition of Rho-associated coiled-coil forming kinases (ROCKs) reduces allergic airway responses in mice. The purpose of this study was to determine the roles of the two ROCK isoforms, ROCK1 and ROCK2, in these responses. Wildtype (WT) mice and heterozygous ROCK1 and ROCK2 knockout mice (ROCK1(+/-) and ROCK2(+/-), respectively) were sensitised and challenged with ovalbumin. ROCK expression and activation were assessed by western blotting. Airway responsiveness was measured by forced oscillation. Bronchoalveolar lavage was performed and the lungs were fixed for histological assessment. Compared with WT mice, ROCK1 and ROCK2 expression were 50% lower in lungs of ROCK1(+/-) and ROCK2(+/-) mice, respectively, without changes in the other isoform. In WT lungs, ROCK activation increased after ovalbumin challenge and was sustained for several hours. This activation was reduced in ROCK1(+/-) and ROCK2(+/-) lungs. Airway responsiveness was comparable in WT, ROCK1(+/-), and ROCK2(+/-) mice challenged with PBS. Ovalbumin challenge caused airway hyperresponsiveness in WT, but not ROCK1(+/-) or ROCK2(+/-) mice. Lavage eosinophils and goblet cell hyperplasia were significantly reduced in ovalbumin-challenged ROCK1(+/-) and ROCK2(+/-) versus WT mice. Ovalbumin-induced changes in lavage interleukin-13, interleukin-5 and lymphocytes were also reduced in ROCK1(+/-) mice. In conclusion, both ROCK1 and ROCK2 are important in regulating allergic airway responses. PMID:21565918

  11. Airway Surface Mycosis in Chronic Th2-Associated Airway Disease

    PubMed Central

    Porter, Paul; Lim, Dae Jun; Maskatia, Zahida Khan; Mak, Garbo; Tsai, Chu-Lin; Citardi, Martin J; Fakhri, Samer; Shaw, Joanne L.; Fothergil, Annette; Kheradmand, Farrah; Corry, David B; Luong, Amber

    2014-01-01

    Background Environmental fungi have been linked to T helper type 2 (Th2) cell-related airway inflammation and the Th2-associated chronic airway diseases asthma, chronic rhinosinusitis with nasal polyps (CRSwNP) and allergic fungal rhinosinusitis (AFRS), but whether these organisms participate directly or indirectly in disease pathology remains unknown. Objective To determine the frequency of fungus isolation and fungus-specific immunity in Th2-associated and non-associated airway disease patients. Methods Sinus lavage fluid and blood were collected from sinus surgery patients (n=118) including CRS patients with and without nasal polyps and AFRS and non-CRS/non-asthmatic control patients. Asthma status was deteremined from medical history. Sinus lavage fluids were cultured and directly examined for evidence of viable fungi. Peripheral blood mononuclear cells were restimulated with fungal antigens in an enzyme linked immunocell spot (ELISpot) assay to determine total memory fungus-specific IL-4-secreting cells. These data were compared to fungus-specific IgE levels measured from plasma by ELISA. Results Filamentous fungi were significantly more commonly cultured from Th2-associated airway disease subjects (asthma, CRSwNP, or AFRS: n=68) compared to non-Th2-associated control patients (n=31); 74% vs 16% respectively, p<0.001. Both fungus-specific IL-4 ELISpot (n=48) and specific IgE (n=70) data correlated with Th2-associated diseases (sensitivity 73% and specificity 100% vs. 50% and 77%, respectively). Conclusions The frequent isolation of fungi growing directly within the airways accompanied by specific immunity to these organisms only in patients with Th2-associated chronic airway diseases suggests that fungi participate directly in the pathogenesis of these conditions. Efforts to eradicate airway fungi from the airways should be considered in selected patients. Clinical Implications Airway fungi may contribute to the expression of sinusitis with nasal polyps and

  12. A hybrid method for airway segmentation and automated measurement of bronchial wall thickness on CT.

    PubMed

    Xu, Ziyue; Bagci, Ulas; Foster, Brent; Mansoor, Awais; Udupa, Jayaram K; Mollura, Daniel J

    2015-08-01

    Inflammatory and infectious lung diseases commonly involve bronchial airway structures and morphology, and these abnormalities are often analyzed non-invasively through high resolution computed tomography (CT) scans. Assessing airway wall surfaces and the lumen are of great importance for diagnosing pulmonary diseases. However, obtaining high accuracy from a complete 3-D airway tree structure can be quite challenging. The airway tree structure has spiculated shapes with multiple branches and bifurcation points as opposed to solid single organ or tumor segmentation tasks in other applications, hence, it is complex for manual segmentation as compared with other tasks. For computerized methods, a fundamental challenge in airway tree segmentation is the highly variable intensity levels in the lumen area, which often causes a segmentation method to leak into adjacent lung parenchyma through blurred airway walls or soft boundaries. Moreover, outer wall definition can be difficult due to similar intensities of the airway walls and nearby structures such as vessels. In this paper, we propose a computational framework to accurately quantify airways through (i) a novel hybrid approach for precise segmentation of the lumen, and (ii) two novel methods (a spatially constrained Markov random walk method (pseudo 3-D) and a relative fuzzy connectedness method (3-D)) to estimate the airway wall thickness. We evaluate the performance of our proposed methods in comparison with mostly used algorithms using human chest CT images. Our results demonstrate that, on publicly available data sets and using standard evaluation criteria, the proposed airway segmentation method is accurate and efficient as compared with the state-of-the-art methods, and the airway wall estimation algorithms identified the inner and outer airway surfaces more accurately than the most widely applied methods, namely full width at half maximum and phase congruency. PMID:26026778

  13. Using optical coherence tomography (OCT) imaging in the evaluation of airway dynamics (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Szabari, Margit V.; Kelly, Vanessa J.; Applegate, Matthew B.; Chee, Chunmin; Tan, Khay M.; Hariri, Lida P.; Harris, R. Scott; Winkler, Tilo; Suter, Melissa J.

    2016-03-01

    Asthma is a chronic disease resulting in periodic attacks of coughing and wheezing due to temporarily constricted and clogged airways. The pathophysiology of asthma and the process of airway narrowing are not completely understood. Appropriate in vivo imaging modality with sufficient spatial and temporal resolution to dynamically assess the behavior of airways is missing. Optical coherence tomography (OCT) enables real-time evaluation of the airways during dynamic and static breathing maneuvers. Our aim was to visualize the structure and function of airways in healthy and Methacholine (MCh) challenged lung. Sheep (n=3) were anesthetized, mechanically ventilated and imaged with OCT in 4 dependent and 4 independent airways both pre- and post-MCh administration. The OCT system employed a 2.4 Fr (0.8 mm diameter) catheter and acquired circumferential cross-sectional images in excess of 100 frames per second during dynamic tidal breathing, 20 second static breath-holds at end-inspiration and expiration pressure, and in a response to a single deep inhalation. Markedly different airway behavior was found in dependent versus non-dependent airway segments before and after MCh injection. OCT is a non-ionizing light-based imaging modality, which may provide valuable insight into the complex dynamic behavior of airway structure and function in the normal and asthmatic lung.

  14. Different airway inflammatory responses in asthmatic and healthy humans exposed to diesel.

    PubMed

    Stenfors, N; Nordenhäll, C; Salvi, S S; Mudway, I; Söderberg, M; Blomberg, A; Helleday, R; Levin, J O; Holgate, S T; Kelly, F J; Frew, A J; Sandström, T

    2004-01-01

    Particulate matter (PM) pollution adversely affects the airways, with asthmatic subjects thought to be especially sensitive. The authors hypothesised that exposure to diesel exhaust (DE), a major source of PM, would induce airway neutrophilia in healthy subjects, and that either these responses would be exaggerated in subjects with mild allergic asthma, or DE would exacerbate pre-existent allergic airways. Healthy and mild asthmatic subjects were exposed for 2 h to ambient levels of DE (particles with a 50% cut-off aerodynamic diameter of 10 microm (PM10) 108 microg x m(-3)) and lung function and airway inflammation were assessed. Both groups showed an increase in airway resistance of similar magnitude after DE exposure. Healthy subjects developed airway inflammation 6 h after DE exposure, with airways neutrophilia and lymphocytosis together with an increase in interleukin-8 (IL-8) protein in lavage fluid, increased IL-8 messenger ribonucleic acid expression in the bronchial mucosa and upregulation of the endothelial adhesion molecules. In asthmatic subjects, DE exposure did not induce a neutrophilic response or exacerbate their pre-existing eosinophilic airway inflammation. Epithelial staining for the cytokine IL-10 was increased after DE in the asthmatic group. Differential effects on the airways of healthy subjects and asthmatics of particles with a 50% cut-off aerodynamic diameter of 10 microm at concentrations below current World Health Organisation air quality standards have been observed in this study. Further work is required to elucidate the significance of these differential responses. PMID:14738236

  15. Airway management in patients with deep neck infections: A retrospective analysis.

    PubMed

    Cho, Soo Young; Woo, Jae Hee; Kim, Yoon Jin; Chun, Eun Hee; Han, Jong In; Kim, Dong Yeon; Baik, Hee Jung; Chung, Rack Kyung

    2016-07-01

    Securing the airway in patients undergoing surgical intervention to control a deep neck infection (DNI) is challenging for anesthesiologists due to the distorted airway anatomy, limited mouth opening, tissue edema, and immobility. It is critical to assess the risk of a potential difficult airway and prepare the most appropriate airway management method.We reviewed our anesthetic experiences managing patients with DNIs, focusing on the need for video-laryngoscope or awake fiberoptic intubation beyond a standard intubation from the anesthesiologist's perspective.When patients had infections in the masticatory space, mouth of floor, oropharyngeal mucosal space, or laryngopharynx, their airways tended to be managed using methods requiring more effort by the anesthesiologists, and more extensive equipment preparation, compared with use of a standard laryngoscope. The degree to which the main lesion influenced the airway anatomy, especially at the level of epiglottis and aryepiglottic fold was related to the airway management method selected.When managing the airways of patients undergoing surgery for DNIs under general anesthesia, anesthesiologists should use imaging with computed tomography to evaluate the preoperative airway status and a comprehensive understanding of radiological findings, comorbidities, and patients' symptoms is needed. PMID:27399122

  16. Tachykinin antagonists and the airways.

    PubMed

    Joos, G F; Kips, J C; Peleman, R A; Pauwels, R A

    1995-01-01

    There is now convincing evidence for the presence of substance P (SP) and neurokinin A (NKA) in human airway nerves. Studies on autopsy tissue, on bronchoalveolar lavage fluid and on sputum suggest that SP may be present in increased amounts in the asthmatic airway. Substance P and NKA are potent bronchoconstrictors of human airways, asthmatics being more sensitive than normal persons. The major enzyme responsible for the degradation of the tachykinins, the neutral endopeptidase, is present in the airways and is involved in the breakdown of exogenously administered SP and NKA, both in normal and asthmatic persons. Other, less well documented airway effects of SP and NKA include mucus secretion, vasodilation and plasma extravasation, as well as the chemoattraction and stimulation of various cells presumed to be involved in asthmatic airway inflammation. NK2 receptors and, to a lesser extent, NK1 receptors have been shown to be involved in bronchoconstriction, whereas NK1 receptors were found to be involved in mucus secretion, microvascular leakage and vasodilatation, and in most of the effects on inflammatory cells. The first clinical trial with FK224, a peptide NK1 and NK2 receptor antagonist, and CP99994, a nonpeptide NK1 receptor antagonist, are negative. However, FK224 failed to block the bronchoconstrictor effect of NKA in asthmatics and the dose of CP99994, needed to antagonize tachykinin effects in man, remains to be determined. PMID:7543746

  17. Surfactant and allergic airway inflammation.

    PubMed

    Winkler, Carla; Hohlfeld, Jens M

    2013-01-01

    Pulmonary surfactant is a complex mixture of unique proteins and lipids that covers the airway lumen. Surfactant prevents alveolar collapse and maintains airway patency by reducing surface tension at the air-liquid interface. Furthermore, it provides a defence against antigen uptake by binding foreign particles and enhancing cellular immune responses. Allergic asthma is associated with chronic airway inflammation and presents with episodes of airway narrowing. The pulmonary inflammation and bronchoconstriction can be triggered by exposure to allergens or pathogens present in the inhaled air. Pulmonary surfactant has the potential to interact with various immune cells which orchestrate allergen- or pathogen-driven episodes of airway inflammation. The complex nature of surfactant allows multiple sites of interaction, but also makes it susceptible to external alterations, which potentially impair its function. This duality of modulating airway physiology and immunology during inflammatory conditions, while at the same time being prone to alterations accompanied by restricted function, has stimulated numerous studies in recent decades, which are reviewed in this article. PMID:23896983

  18. Airway gene transfer in a non-human primate: lentiviral gene expression in marmoset lungs.

    PubMed

    Farrow, N; Miller, D; Cmielewski, P; Donnelley, M; Bright, R; Parsons, D W

    2013-01-01

    Genetic therapies for cystic fibrosis (CF) must be assessed for safety and efficacy, so testing in a non-human primate (NHP) model is invaluable. In this pilot study we determined if the conducting airways of marmosets (n = 2) could be transduced using an airway pre-treatment followed by an intratracheal bolus dose of a VSV-G pseudotyped HIV-1 based lentiviral (LV) vector (LacZ reporter). LacZ gene expression (X-gal) was assessed after 7 days and found primarily in conducting airway epithelia as well as in alveolar regions. The LacZ gene was not detected in liver or spleen via qPCR. Vector p24 protein bio-distribution into blood was transient. Dosing was well tolerated. This preliminary study confirmed the transducibility of CF-relevant airway cell types. The marmoset is a promising NHP model for testing and translating genetic treatments for CF airway disease towards clinical trials. PMID:23412644

  19. High glucose induces dysfunction of airway epithelial barrier through down-regulation of connexin 43.

    PubMed

    Yu, Hongmei; Yang, Juan; Zhou, Xiangdong; Xiao, Qian; Lü, Yang; Xia, Li

    2016-03-01

    The airway epithelium is a barrier to the inhaled antigens and pathogens. Connexin 43 (Cx43) has been found to play critical role in maintaining the function of airway epithelial barrier and be involved in the pathogenesis of the diabetic retinal vasculature, diabetes nephropathy and diabetes skin. Hyperglycemia has been shown to be an independent risk factor for respiratory infections. We hypothesize that the down-regulation of Cx43 induced by HG alters the expression of tight junctions (zonula occludens-1 (ZO-1) and occludin) and contributes to dysfunction of airway epithelial barrier, and Cx43 plays a critical role in the process in human airway epithelial cells (16 HBE). We show that high glucose (HG) decreased the expression of ZO-1 and occludin, disassociated interaction between Cx43 and tight junctions, and then increased airway epithelial transepithelial electrical resistance (TER) and permeability by down-regulation of Cx43 in human airway epithelial cells. These observations demonstrate an important role for Cx43 in regulating HG-induced dysfunction of airway epithelial barrier. These findings may bring new insights into the molecular pathogenesis of pulmonary infection related to diabetes mellitus and lead to novel therapeutic intervention for the dysfunction of airway epithelial barrier in chronic inflammatory airway diseases. PMID:26902399

  20. DNA Methylation Is Globally Disrupted and Associated with Expression Changes in Chronic Obstructive Pulmonary Disease Small Airways

    PubMed Central

    Chari, Raj; Thu, Kelsie L.; Wilson, Ian M.; Cotton, Allison M.; Kennett, Jennifer Y.; Zhang, May; Lonergan, Kim M.; Steiling, Katrina; Brown, Carolyn J.; McWilliams, Annette; Ohtani, Keishi; Lenburg, Marc E.; Sin, Don D.; Spira, Avrum; MacAulay, Calum E.; Lam, Stephen; Lam, Wan L.

    2014-01-01

    DNA methylation is an epigenetic modification that is highly disrupted in response to cigarette smoke and involved in a wide spectrum of malignant and nonmalignant diseases, but surprisingly not previously assessed in small airways of patients with chronic obstructive pulmonary disease (COPD). Small airways are the primary sites of airflow obstruction in COPD. We sought to determine whether DNA methylation patterns are disrupted in small airway epithelia of patients with COPD, and evaluate whether changes in gene expression are associated with these disruptions. Genome-wide methylation and gene expression analysis were performed on small airway epithelial DNA and RNA obtained from the same patient during bronchoscopy, using Illumina’s Infinium HM27 and Affymetrix’s Genechip Human Gene 1.0 ST arrays. To control for known effects of cigarette smoking on DNA methylation, methylation and gene expression profiles were compared between former smokers with and without COPD matched for age, pack-years, and years of smoking cessation. Our results indicate that aberrant DNA methylation is (1) a genome-wide phenomenon in small airways of patients with COPD, and (2) associated with altered expression of genes and pathways important to COPD, such as the NF-E2–related factor 2 oxidative response pathway. DNA methylation is likely an important mechanism contributing to modulation of genes important to COPD pathology. Because these methylation events may underlie disease-specific gene expression changes, their characterization is a critical first step toward the development of epigenetic markers and an opportunity for developing novel epigenetic therapeutic interventions for COPD. PMID:24298892

  1. Human airway smooth muscle cells secrete amphiregulin via bradykinin/COX-2/PGE2, inducing COX-2, CXCL8, and VEGF expression in airway epithelial cells

    PubMed Central

    Knox, Alan J.

    2015-01-01

    Human airway smooth muscle cells (HASMC) contribute to asthma pathophysiology through an increased smooth muscle mass and elevated cytokine/chemokine output. Little is known about how HASMC and the airway epithelium interact to regulate chronic airway inflammation and remodeling. Amphiregulin is a member of the family of epidermal growth factor receptor (EGFR) agonists with cell growth and proinflammatory roles and increased expression in the lungs of asthma patients. Here we show that bradykinin (BK) stimulation of HASMC increases amphiregulin secretion in a mechanism dependent on BK-induced COX-2 expression, increased PGE2 output, and the stimulation of HASMC EP2 and EP4 receptors. Conditioned medium from BK treated HASMC induced CXCL8, VEGF, and COX-2 mRNA and protein accumulation in airway epithelial cells, which were blocked by anti-amphiregulin antibodies and amphiregulin siRNA, suggesting a paracrine effect of HASMC-derived amphiregulin on airway epithelial cells. Consistent with this, recombinant amphiregulin induced CXCL8, VEGF, and COX-2 in airway epithelial cells. Finally, we found that conditioned media from amphiregulin-stimulated airway epithelial cells induced amphiregulin expression in HASMC and that this was dependent on airway epithelial cell COX-2 activity. Our study provides evidence of a dynamic axis of interaction between HASMC and epithelial cells that amplifies CXCL8, VEGF, COX-2, and amphiregulin production. PMID:26047642

  2. Airway inflammation, airway responsiveness and cough before and after inhaled budesonide in patients with eosinophilic bronchitis.

    PubMed

    Brightling, C E; Ward, R; Wardlaw, A J; Pavord, I D

    2000-04-01

    Eosinophilic bronchitis is a common cause of chronic cough, characterized by sputum eosinophilia similar to that seen in asthma, but unlike asthma the patients have no objective evidence of variable airflow obstruction or airway hyperresponsiveness. The reason for the different functional associations is unclear. The authors have tested the hypothesis that in eosinophilic bronchitis the inflammation is mainly localized in the upper airway. In an open study the authors measured the lower (provocative concentration causing a 20% fall in forced expiratory volume in one second (PC20)) and upper (PC25 MIF50) airway responsiveness to histamine, lower and upper airway inflammation using induced sputum and nasal lavage, in II patients with eosinophilic bronchitis. The authors assessed changes in these measures and in cough reflex sensitivity to capsaicin and cough severity after 400 microg of inhaled budesonide for 4 weeks. A nasal eosinophilia was present in only three patients with one having upper airway hyperresponsiveness. Following treatment with inhaled corticosteroids the geometric mean sputum eosinophil count decreased from 12.8% to 2.9% (mean difference 4.4-fold, 95% confidence interval (CI) 2.14-10.02), the mean +/- sem cough visual analogue score on a 100 mm scale decreased from 27.2 +/- 6.6 mm to 12.6 +/- 5.7 mm (mean difference 14.6, 95% CI 9.1-20.1) and the cough sensitivity assessed as the capsaicin concentration required to cause two coughs (C2) and five coughs (C5) improved (C2 mean difference 0.75 doubling concentrations, 95% CI 0.36-1.1; C5 mean difference 1.3 doubling concentration, 95% CI 0.6-2.1). There was a significant positive correlation between the fold change in sputum eosinophil count and doubling dose change in C5 after inhaled budesonide (r=0.61). It is concluded that upper airway inflammation is not prominent in eosinophilic bronchitis and that inhaled budesonide improves the sputum eosinophilia, cough severity and sensitivity suggesting a

  3. Oral and Airway Microbiota in HIV-Infected Pneumonia Patients

    PubMed Central

    Iwai, Shoko; Fei, Matthew; Huang, Delphine; Fong, Serena; Subramanian, Anuradha; Grieco, Katherine

    2012-01-01

    Despite the increased frequency of recurrent pneumonia in HIV-infected patients and recent studies linking the airway bacterial community (microbiota) to acute and chronic respiratory infection, little is known of the oral and airway microbiota that exist in these individuals and their propensity to harbor pathogens despite antimicrobial treatment for acute pneumonia. This pilot study compared paired samples of the oral and airway microbiota from 15 hospitalized HIV-infected patients receiving antimicrobial treatment for acute pneumonia. Total DNA was extracted, bacterial burden was assessed by quantitative PCR, and amplified 16S rRNA was profiled for microbiome composition using a phylogenetic microarray (16S rRNA PhyloChip). Though the bacterial burden of the airway was significantly lower than that of the oral cavity, microbiota in both niches were comparably diverse. However, oral and airway microbiota exhibited niche specificity. Oral microbiota were characterized by significantly increased relative abundance of multiple species associated with the mouth, including members of the Bacteroides, Firmicutes, and TM7 phyla, while airway microbiota were primarily characterized by a relative expansion of the Proteobacteria. Twenty-two taxa were detected in both niches, including Streptococcus bovis and Chryseobacterium species, pathogens associated with HIV-infected populations. In addition, we compared the airway microbiota of five of these patients to those of five non-HIV-infected pneumonia patients from a previous study. Compared to the control population, HIV-infected patients exhibited relative increased abundance of a large number of phylogenetically distinct taxa, which included several known or suspected pathogenic organisms, suggesting that recurrent pneumonia in HIV-infected populations may be related to the presence of these species. PMID:22760045

  4. INTEGRATED CT/BRONCHOSCOPY IN THE CENTRAL AIRWAYS: PRELIMINARY RESULTS

    PubMed Central

    Suter, Melissa J.; Reinhardt, Joseph M.; McLennan, Geoffrey

    2009-01-01

    Rationale and Objectives Many imaging modalities and methodologies exist for evaluating the pulmonary airways. Individually, each modality provides insight to the state of the airways however, alone they do not necessary provide a comprehensive description. The goal of this paper is to integrate complementary medical imaging datasets to form a synergistic description of the airways. Materials and Methods Two digital bronchoscopy techniques were used to evaluate the pulmonary mucosa. A digital color bronchoscopy system was used to detect mucosal color alterations, and a fluorescence detection system was used to assess the microvasculature of the bronchial mucosa. Study participants were also imaged with a multi-detector row computed tomography (MDCT) scanner. Virtual bronchoscopy and image registration techniques were exploited to combine 3D surface renderings, extracted from the MDCT data, together with the 2D digital bronchoscopy images. Validation of the fusion process was performed on a rubber phantom of an adult airway with 4 embedded metal beads. Results The fusion of the MDCT extracted airway tree and the digital bronchoscopy datasets were presented for 3 study participants. In addition, the detected accuracy of the registration method to reliably align the MDCT and bronchoscopy image datasets was determined to be 1.98 mm in the phantom airway model. Conclusion We have demonstrated that merging of three distinct digital datasets to provide a single synergistic description of the airways is possible. This is a pilot project in the field of eidomics, the process of combining digital image datasets and image based processes together. We anticipate that in the future eidomics will provide a universal and predictive imaging language that will change health care delivery. PMID:18486014

  5. Obliterative airway remodelling in transplanted and non-transplanted lungs.

    PubMed

    Jonigk, Danny; Theophile, Katharina; Hussein, Kais; Bock, Oliver; Lehmann, Ulrich; Bockmeyer, Clemens L; Gottlieb, Jens; Fischer, Stefan; Simon, Andre; Welte, Tobias; Maegel, Lavinia; Kreipe, Hans; Laenger, Florian

    2010-09-01

    Obliterative airway remodelling is a morphological sequence in a variety of pulmonary diseases. Notably, bronchiolitis obliterans represents one of the key complications of lung transplantation, induced by (immigrating) myofibroblasts. A comparative expression analysis of obliterative airway remodelling in transplanted and non-transplanted patients has not been reported so far. Obliterated and unremodelled airways from explanted lungs (n = 19) from patients suffering from chronic allograft dysfunction, infection, graft-versus-host disease and toxic exposure were isolated by laser-assisted microdissection. Airways from lung allografts harvested shortly before and after transplantation (n = 4) as well as fibroblastic foci from lungs with interstitial pulmonary fibrosis (n = 4) served as references. Pre-amplified cDNA was analysed by quantitative real-time RT-PCR for expression of fibrosis, inflammation and apoptosis-associated genes. Composition of infiltrating cells and protein expression were assessed by conventional histology and immunohistochemistry. Bronchiolitis obliterans in transplanted patients showed a significant increase of BMP-7 expression (p = 0.0141 compared with controls), while TGF-beta1 and FGF-2 as well as BMP-4 and BMP-7 were up-regulated in fibroblastic foci in interstitial pulmonary fibrosis (p < 0.0424 compared with controls). Regarding other fibrosis-associated genes (BMP-6, SMAD-3, CASP-3 and CASP-9, FASLG, NF-KB1, IL-1 and IL-2) as well as cellularity and cellular composition, no significant differences between obliterative airway remodelling in transplanted and non-transplanted patients could be shown. Obliterative airway remodelling in lung allografts and in non-transplanted patients share many morphological and genetic traits. BMPs, especially BMP-7, warrant further investigation as possible markers for the aggravation of airway remodelling. PMID:20632031

  6. Comparing the Laryngeal Mask Airway, Cobra Perilaryngeal Airway and Face Mask in Children Airway Management

    PubMed Central

    Tekin, Beyza; Hatipoğlu, Zehra; Türktan, Mediha; Özcengiz, Dilek

    2016-01-01

    Objective We compared the effects of the laryngeal mask airway (LMA), face mask and Cobra perilaryngeal airway (PLA) in the airway management of spontaneously breathing paediatric patients undergoing elective inguinal surgery. Methods In this study, 90 cases of 1–14-year-old children undergoing elective inguinal surgery were scheduled. The patients were randomly divided into three groups. Anaesthesia was provided with sevoflurane and 50%–50% nitrous oxide and oxygen. After providing an adequate depth of anaesthesia, supraglottic airway devices were inserted in the group I and II patients. The duration and number of insertion, haemodynamic parameters, plateau and peak inspiratory pressure and positive end-expiratory pressure of the patients were recorded preoperatively, after induction and at 5, 10, 15 and 30 min peroperatively. Results There were no statistical differences between the groups in terms of haemodynamic parameters (p>0.05). In group II, instrumentation success was higher and instrumentation time was shorter than group II. The positive end-expiratory pressure and plateau and peak inspiratory pressure values were statistically lower in group II (p<0.05). Conclusion We concluded that for airway safety and to avoid possible complications, LMA and Cobra PLA could be alternatives to face mask and that the Cobra PLA provided lower airway pressure and had a faster and more easy placement than LMA. PMID:27366563

  7. Human airway ciliary dynamics

    PubMed Central

    Thompson, Kristin; Knowles, Michael R.; Davis, C. William

    2013-01-01

    Airway cilia depend on precise changes in shape to transport the mucus gel overlying mucosal surfaces. The ciliary motion can be recorded in several planes using video microscopy. However, cilia are densely packed, and automated computerized systems are not available to convert these ciliary shape changes into forms that are useful for testing theoretical models of ciliary function. We developed a system for converting planar ciliary motions recorded by video microscopy into an empirical quantitative model, which is easy to use in validating mathematical models, or in examining ciliary function, e.g., in primary ciliary dyskinesia (PCD). The system we developed allows the manipulation of a model cilium superimposed over a video of beating cilia. Data were analyzed to determine shear angles and velocity vectors of points along the cilium. Extracted waveforms were used to construct a composite waveform, which could be used as a standard. Variability was measured as the mean difference in position of points on individual waveforms and the standard. The shapes analyzed were the end-recovery, end-effective, and fastest moving effective and recovery with mean (± SE) differences of 0.31(0.04), 0.25(0.06), 0.50(0.12), 0.50(0.10), μm, respectively. In contrast, the same measures for three different PCD waveforms had values far outside this range. PMID:23144323

  8. ASSESSMENT OF RISK FACTORS FOR DIABETES MELLITUS TYPE 2

    PubMed Central

    Begic, Edin; Arnautovic, Amira; Masic, Izet

    2016-01-01

    Introduction: Diabetes is a group of metabolic diseases characterized by hyperglycemia, and represents a disease of the modern age, disease of the 21st century. Prevention of this disease is listed as imperative. Aim of this article was to evaluate questionnaires on the assessment of risk factors for Diabetes Mellitus type 2. Material and Methods: A total of 540 questionnaires handed out randomly to citizens of Canton Sarajevo of all ages, sexes and educational levels (in January 2016) were analyzed. Results: Analyzed questionnaires showed relatively low risk of getting diabetes in the next ten years in the majority of the population. These results are rather encouraging but may in some way be in confrontation with the statistics which show a rapid outburst of diabetes. Conclusion: The life-style is the main reason for such a thing to happen, and looking at these questionnaires, we might get the feeling that we really do live in a, conditionally speaking, physically active society. That, from our everyday experience is not entirely true. It would be wise to continue doing research on this topic on the territory of Bosnia and Herzegovina. PMID:27482159

  9. Assessing Diet as a Modifiable Risk Factor for Pesticide Exposure

    PubMed Central

    Oates, Liza; Cohen, Marc

    2011-01-01

    The effects of pesticides on the general population, largely as a result of dietary exposure, are unclear. Adopting an organic diet appears to be an obvious solution for reducing dietary pesticide exposure and this is supported by biomonitoring studies in children. However, results of research into the effects of organic diets on pesticide exposure are difficult to interpret in light of the many complexities. Therefore future studies must be carefully designed. While biomonitoring can account for differences in overall exposure it cannot necessarily attribute the source. Due diligence must be given to appropriate selection of participants, target pesticides and analytical methods to ensure that the data generated will be both scientifically rigorous and clinically useful, while minimising the costs and difficulties associated with biomonitoring studies. Study design must also consider confounders such as the unpredictable nature of chemicals and inter- and intra-individual differences in exposure and other factors that might influence susceptibility to disease. Currently the most useful measures are non-specific urinary metabolites that measure a range of organophosphate and synthetic pyrethroid insecticides. These pesticides are in common use, frequently detected in population studies and may provide a broader overview of the impact of an organic diet on pesticide exposure than pesticide-specific metabolites. More population based studies are needed for comparative purposes and improvements in analytical methods are required before many other compounds can be considered for assessment. PMID:21776202

  10. Role of Small Airways in Asthma.

    PubMed

    Finkas, Lindsay K; Martin, Richard

    2016-08-01

    Asthma is an inflammatory condition of both the small and large airways. Recently the small airways have gained attention as studies have shown significant inflammation in the small airways in all severities of asthma. This inflammation has correlated with peripheral airway resistance and as a result, noninvasive methods to reliably measure small airways have been pursued. In addition, recent changes in asthma inhalers have led to alterations in drug formulations and the development of extrafine particle inhalers that improve delivery to the distal airways. PMID:27401620

  11. Computer-Based Assessment of Cognition: The ETS Factor Kit.

    ERIC Educational Resources Information Center

    Ekstrom, Ruth B.; Bejar, Isaac I.

    The history of the Educational Testing Service (ETS) Factor Kits is summarized. The original ETS Factor Kit was developed in 1954 and contained 51 items, three each for each of 15 factors and six for a 16th factor. The next edition was developed in 1963 and included adaptations (clones) of the defining tests instead of the exact copies. These…

  12. Platelet-derived-growth-factor stimulation of the p42/p44 mitogen-activated protein kinase pathway in airway smooth muscle: role of pertussis-toxin-sensitive G-proteins, c-Src tyrosine kinases and phosphoinositide 3-kinase.

    PubMed Central

    Conway, A M; Rakhit, S; Pyne, S; Pyne, N J

    1999-01-01

    The mechanism used by the platelet-derived growth factor receptor (PDGFR) to activate the mitogen-activated- protein-kinase (p42/p44 MAPK) pathway was investigated in cultured airway smooth muscle (ASM) cells. We have found that pertussis toxin (PTX, which was used to inactivate the heterotrimeric G-protein Gi) induced an approx. 40-50% decrease in the activation of c-Src and p42/p44 MAPK by PDGF. An essential role for c-Src was confirmed using the c-Src inhibitor, PP1, which abolished p42/p44 MAPK activation (PP1 and PTX were without effect on PDGFR tyrosine phosphorylation). Furthermore, the PTX-dependent decrease in c-Src and p42/p44 MAPK activation appeared correlated. These findings suggest that the PDGFR can utilize the PTX-sensitive G-protein, Gi, to regulate c-Src and subsequent p42/p44 MAPK activation. Phosphoinositide 3-kinase (PI3K) has been shown by others to be involved in p42/p44 MAPK activation. This is confirmed here by experiments which showed that PI3K inhibitors (wortmannin and LY294002) reduced the activation of p42/p44 MAPK by PDGF. PI3K activity was increased in Grb-2 immunoprecipitates from PDGF-stimulated cells and was decreased by pretreating these cells with PTX. These findings show that Gi might also promote Grb-2-PI3K complex formation and that Grb-2 may be a site at which PI3K is integrated into the p42/p44 MAPK cascade. In conclusion, our results demonstrate that Gi enables the PDGFR to signal more efficiently to p42/p44 MAPK, and this appears to be achieved through the regulation of c-Src and Grb-2/PI3K, which are intermediates in the p42/p44 MAPK cascade. PMID:9882612

  13. An Exploratory Investigation of the Factor Structure of the Reynolds Intellectual Assessment Scales (RIAS)

    ERIC Educational Resources Information Center

    Dombrowski, Stefan C.; Watkins, Marley W.; Brogan, Michael J.

    2009-01-01

    This study investigated the factor structure of the Reynolds Intellectual Assessment Scales (RIAS) using rigorous exploratory factor analytic and factor extraction procedures. The results of this study indicate that the RIAS is a single factor test. Despite these results, higher order factor analysis using the Schmid-Leiman procedure indicates…

  14. The anaesthetic assessment, management and risk factors of bariatric surgical patients requiring postoperative intensive care support: a state-wide, five-year cohort study.

    PubMed

    Morgan, D J R; Ho, K M

    2016-03-01

    Bariatric surgery is a rapidly growing and dynamic discipline necessitating a specialised anaesthetic approach coordinating high-risk patients with appropriate post-operative intensive care (ICU) support. The relationship between the anaesthetic and ICU utilisation after bariatric surgery is poorly understood. All adult bariatric surgery patients admitted to any ICU over a five-year period between 2007 and 2011 in Western Australia were identified from hospital admission records and cross-referenced against the Western Australian Department of Health Data Linkage Unit database. During the study period 12,062 patients under went bariatric surgery with 581 (4.8%) patients admitted to ICU immediately following surgery. The mean pre-operative ASA score was 3.3 [standard deviation 1.1] with 76.9% of patients were assessed by their anaesthetist for the first time on the day-of-surgery. Blood pathology (75%) and ECG (46.3%) were the most common preoperative investigations. Intra-operatively, 2.1% of patients had a grade 4 intubation with only 3.4% of patients requiring a videoscopic assisted intubation. Despite being deemed at high risk, 23.6% of patients were managed with 20 gauge or smaller intravenous access. Anaesthetic complications were extremely uncommon (0.5% of all bariatric cases) but accounted for 9.7% of all postoperative ICU admissions. Smoking history, but not body-mass-index (P=0.46), was the only significant prognostic factor for respiratory or airway related anaesthetic complications (P=0.012). In summary, the anaesthesia management of bariatric surgery varied widely in Western Australia, with smoking as the only significant preoperative risk factor for respiratory or airway related anaesthesia complications. PMID:27029656

  15. Aspergillus fumigatus Invasion Increases with Progressive Airway Ischemia

    PubMed Central

    Hsu, Joe L.; Khan, Mohammad A.; Sobel, Raymond A.; Jiang, Xinguo; Clemons, Karl V.; Nguyen, Tom T.; Stevens, David A.; Martinez, Marife; Nicolls, Mark R.

    2013-01-01

    Despite the prevalence of Aspergillus-related disease in immune suppressed lung transplant patients, little is known of the host-pathogen interaction. Because of the mould’s angiotropic nature and because of its capacity to thrive in hypoxic conditions, we hypothesized that the degree of Aspergillus invasion would increase with progressive rejection-mediated ischemia of the allograft. To study this relationship, we utilized a novel orthotopic tracheal transplant model of Aspergillus infection, in which it was possible to assess the effects of tissue hypoxia and ischemia on airway infectivity. Laser Doppler flowmetry and FITC-lectin were used to determine blood perfusion, and a fiber optic microsensor was used to measure airway tissue oxygen tension. Fungal burden and depth of invasion were graded using histopathology. We demonstrated a high efficacy (80%) for producing a localized fungal tracheal infection with the majority of infection occurring at the donor-recipient anastomosis; Aspergillus was more invasive in allogeneic compared to syngeneic groups. During the study period, the overall kinetics of both non-infected and infected allografts was similar, demonstrating a progressive loss of perfusion and oxygenation, which reached a nadir by days 10-12 post-transplantation. The extent of Aspergillus invasion directly correlated with the degree of graft hypoxia and ischemia. Compared to the midtrachea, the donor-recipient anastomotic site exhibited lower perfusion and more invasive disease; a finding consistent with clinical experience. For the first time, we identify ischemia as a putative risk factor for Aspergillus invasion. Therapeutic approaches focused on preserving vascular health may play an important role in limiting Aspergillus infections. PMID:24155924

  16. Higher-Order Exploratory Factor Analysis of the Reynolds Intellectual Assessment Scales with a Referred Sample

    ERIC Educational Resources Information Center

    Nelson, Jason M.; Canivez, Gary L.; Lindstrom, Will; Hatt, Clifford V.

    2007-01-01

    The factor structure of the Reynolds Intellectual Assessment Scales (RIAS; [Reynolds, C.R., & Kamphaus, R.W. (2003). "Reynolds Intellectual Assessment Scales". Lutz, FL: Psychological Assessment Resources, Inc.]) was investigated with a large (N=1163) independent sample of referred students (ages 6-18). More rigorous factor extraction criteria…

  17. High-fat diet promotes lung fibrosis and attenuates airway eosinophilia after exposure to cockroach allergen in mice.

    PubMed

    Ge, Xiao Na; Greenberg, Yana; Hosseinkhani, M Reza; Long, Eric K; Bahaie, Nooshin S; Rao, Amrita; Ha, Sung Gil; Rao, Savita P; Bernlohr, David A; Sriramarao, P

    2013-11-01

    Obesity is an important risk factor for asthma but the mechanistic basis for this association is not well understood. In the current study, the impact of obesity on lung inflammatory responses after allergen exposure was investigated. C57BL/6 mice maintained on a high-fat diet (HFD) or a normal diet (ND) after weaning were sensitized and challenged with cockroach allergen (CRA). Airway inflammation was assessed based on inflammatory cell recruitment, measurement of lung Th1-Th2 cytokines, chemokines, eicosanoids, and other proinflammatory mediators as well as airway hyperresponsiveness (AHR). CRA-challenged mice fed a HFD exhibited significantly decreased allergen-induced airway eosinophilia along with reduced lung IL-5, IL-13, LTC4, CCL11, and CCL2 levels as well as reduced mucus secretion and smooth muscle mass compared to ND fed mice. However, allergen-challenged HFD fed mice demonstrated significantly increased PAI-1 and reduced PGE2 levels in the lung relative to corresponding ND fed mice. Interestingly, saline-exposed HFD fed mice demonstrated elevated baseline levels of TGF-β1, arginase-1, hypoxia-inducible factor-1α, and lung collagen expression associated with decreased lung function compared to corresponding ND fed mice. These studies indicate that a HFD inhibits airway eosinophilia while altering levels of PAI-1 and PGE2 in response to CRA in mice. Further, a HFD can lead to the development of lung fibrosis even in the absence of allergen exposure which could be due to innate elevated levels of specific profibrotic factors, potentially affecting lung function during asthma. PMID:24102347

  18. Assessment of economic factors affecting the satellite power system. Volume 1: System cost factors

    NASA Technical Reports Server (NTRS)

    Hazelrigg, G. A., Jr.

    1978-01-01

    The factors relevant to SPS costing and selection of preferred SPS satellite configurations were studied. The issues discussed are: (1) consideration of economic factors in the SPS system that relate to selection of SPS satellite configuration; (2) analysis of the proper rate of interest for use in SPS system definition studies; and (3) the impacts of differential inflation on SPS system definition costing procedures. A cost-risk comparison of the SPS satellite configurations showed a significant difference in the levelized cost of power from them. It is concluded, that this difference is the result more of differences in the procedures for assessing costs rather than in the satellite technologies required or of any advantages of one satellite configuration over the other. Analysis of the proper rate of interest for use in SPS system is 4 percent. The major item of differential inflation to be expected over this period of time is the real cost of labor. This cost is likely to double between today and the period of SPS construction.

  19. Airway Fibrinogenolysis and the Initiation of Allergic Inflammation

    PubMed Central

    Millien, Valentine Ongeri; Lu, Wen; Mak, Garbo; Yuan, Xiaoyi; Knight, J. Morgan; Porter, Paul; Kheradmand, Farrah

    2014-01-01

    The past 15 years of allergic disease research have produced extraordinary improvements in our understanding of the pathogenesis of airway allergic diseases such as asthma. Whereas it was previously viewed as largely an immunoglobulin E-mediated process, the gradual recognition that T cells, especially Type 2 T helper (Th2) cells and Th17 cells, play a major role in asthma and related afflictions has inspired clinical trials targeting cytokine-based inflammatory pathways that show great promise. What has yet to be clarified about the pathogenesis of allergic inflammatory disorders, however, are the fundamental initiating factors, both exogenous and endogenous, that drive and sustain B- and T-cell responses that underlie the expression of chronic disease. Here we review how proteinases derived from diverse sources drive allergic responses. A central discovery supporting the proteinase hypothesis of allergic disease pathophysiology is the role played by airway fibrinogen, which in part appears to serve as a sensor of unregulated proteinase activity and which, when cleaved, both participates in a novel allergic signaling pathway through Toll-like receptor 4 and forms fibrin clots that contribute to airway obstruction. Unresolved at present is the ultimate source of airway allergenic proteinases. From among many potential candidates, perhaps the most intriguing is the possibility such enzymes derive from airway fungi. Together, these new findings expand both our knowledge of allergic disease pathophysiology and options for therapeutic intervention. PMID:25525732

  20. Unmet needs in severe chronic upper airway disease (SCUAD).

    PubMed

    Bousquet, Jean; Bachert, Claus; Canonica, Giorgio W; Casale, Thomas B; Cruz, Alvaro A; Lockey, Richard J; Zuberbier, Torsten

    2009-09-01

    Although the majority of patients with chronic upper airway diseases have controlled symptoms during treatment, many patients have severe chronic upper airway diseases (SCUADs). SCUAD defines those patients whose symptoms are inadequately controlled despite adequate (ie, effective, safe, and acceptable) pharmacologic treatment based on guidelines. These patients have impaired quality of life, social functioning, sleep, and school/work performance. Severe uncontrolled allergic rhinitis, nonallergic rhinitis, chronic rhinosinusitis, aspirin-exacerbated respiratory diseases, or occupational airway diseases are defined as SCUADs. Pediatric SCUADs are still unclear. In developing countries SCUADs exist, but risk factors can differ from those seen in developed countries. Comorbidities are common in patients with SCUADs and might increase their severity. The present document is the position of a group of experts considering that SCUADs should be considered differently from mild chronic upper airway diseases. It reviews the state of the art, highlighting gaps in our knowledge, and proposes several areas for a better understanding, prevention, and management of SCUADs. This document can also serve to optimize the pharmacoeconomic evaluation of SCUADs by means of comparison with mild chronic upper airway diseases. PMID:19660803

  1. Regional aerosol deposition in human upper airways. Final report

    SciTech Connect

    Swift, D.L.

    1997-11-01

    During the award period, a number of studies have been carried out related to the overall objective of the project which is to elucidate important factors which influence the upper airway deposition and dose of particles in the size range 0.5 nm - 10 {mu}m, such as particle size, breathing conditions, age, airway geometry, and mode of breathing. These studies are listed below. (1) A high voltage electrospray system was constructed to generate polydispersed 1-10 {mu}m diameter di-ethylhexyl sebacate aerosol for particle deposition studies in nasal casts and in human subjects. (2) The effect of nostril dimensions, nasal passage geometry, and nasal resistance on particle deposition efficiency in forty healthy, nonsmoking adults at a constant flowrate were studied. (3) The effect of nostril dimensions, nasal passage dimensions and nasal resistance on the percentage of particle deposition in the anterior 3 cm of the nasal passage of spontaneously breathing humans were studied. (4) The region of deposition of monodispersed aerosols were studied using replicate casts. (5) Ultrafine aerosol deposition using simulated breath holding path and natural path was compared. (6) An experimental technique was proposed and tested to measure the oral deposition of inhaled ultrafine particles. (7) We have calculated the total deposition fraction of ultrafine aerosols from 5 to 200 n in the extrathoracic airways and in the lung. (8) The deposition fraction of radon progeny in the head airways was studied using several head airway models.

  2. Airway smooth muscle growth from the perspective of animal models.

    PubMed

    Martin, James G; Ramos-Barbón, David

    2003-09-16

    Airway smooth muscle maintains airway tone and may assist in adjusting ventilation distribution within the normal lung. Alterations in the properties or the quantity of ASM are likely responsible for some instances of airways hyperresponsiveness to bronchoconstrictive stimuli that is a characteristic of diseases such as asthma. Morphometric studies have shown an increase in the mass of ASM in human asthmatic airways. Animal models have been developed that confirm that ASM can be induced to grow by allergic sensitization and challenge. Growth is in large part by hyperplasia as measured by incorporation of bromodeoxyuridine as a marker of the S-phase of the cell cycle. T cells, in particular CD4+ cells, may participate in the stimulation of growth of ASM by allergen challenge. The growth factors responsible for the increase in ASM are as yet unidentified but two mediators associated with allergic airway responses, cysteinyl leukotrienes and endothelin, have been implicated using specific receptor antagonists. The links between T cells and the biochemical mediators of growth have not been established. PMID:14516730

  3. Biofilm-dependent airway infections: a role for ambroxol?

    PubMed

    Cataldi, M; Sblendorio, V; Leo, A; Piazza, O

    2014-08-01

    Biofilms are a key factor in the development of both acute and chronic airway infections. Their relevance is well established in ventilator associated pneumonia, one of the most severe complications in critically ill patients, and in cystic fibrosis, the most common lethal genetic disease in Caucasians. Accumulating evidence suggests that biofilms could have also a role in chronic obstructive pulmonary disease and their involvement in bronchiectasis has been proposed as well. When they grow in biofilms, microorganisms become multidrug-resistant. Therefore the treatment of biofilm-dependent airway infections is problematic. Indeed, it still largely based on measures aiming to prevent the formation of biofilms or remove them once that they are formed. Here we review recent evidence suggesting that the mucokinetic drug ambroxol has specific anti-biofilm properties. We also discuss how additional pharmacological properties of this drug could be beneficial in biofilm-dependent airway infections. Specifically, we review the evidence showing that: 1-ambroxol exerts anti-inflammatory effects by inhibiting at multiple levels the activity of neutrophils, and 2-it improves mucociliary clearance by interfering with the activity of airway epithelium ion channels and transporters including sodium/bicarbonate and sodium/potassium/chloride cotransporters, cystic fibrosis transmembrane conductance regulator and aquaporins. As a whole, the data that we review here suggest that ambroxol could be helpful in biofilm-dependent airway infections. However, considering the limited clinical evidence available up to date, further clinical studies are required to support the use of ambroxol in these diseases. PMID:24252805

  4. Mechanisms of BDNF regulation in asthmatic airway smooth muscle.

    PubMed

    Aravamudan, Bharathi; Thompson, Michael A; Pabelick, Christina M; Prakash, Y S

    2016-08-01

    Brain-derived neurotrophic factor (BDNF), a neurotrophin produced by airway smooth muscle (ASM), enhances inflammation effects on airway contractility, supporting the idea that locally produced growth factors influence airway diseases such as asthma. We endeavored to dissect intrinsic mechanisms regulating endogenous, as well as inflammation (TNF-α)-induced BDNF secretion in ASM of nonasthmatic vs. asthmatic humans. We focused on specific Ca(2+) regulation- and inflammation-related signaling cascades and quantified BDNF secretion. We find that TNF-α enhances BDNF release by ASM cells, via several mechanisms relevant to asthma, including transient receptor potential channels TRPC3 and TRPC6 (but not TRPC1), ERK 1/2, PI3K, PLC, and PKC cascades, Rho kinase, and transcription factors cAMP response element binding protein and nuclear factor of activated T cells. Basal BDNF expression and secretion are elevated in asthmatic ASM and increase further with TNF-α exposure, involving many of these regulatory mechanisms. We conclude that airway BDNF secretion is regulated at multiple levels, providing a basis for autocrine effects of BDNF under conditions of inflammation and disease, with potential downstream influences on contractility and remodeling. PMID:27317689

  5. DEFINITION OF AIRWAY COMPOSITION WITHIN GAMMA CAMERA IMAGES

    EPA Science Inventory

    The efficacies on inhaled pharmacologic drugs in the prophylaxis and treatment if airway diseases could be improved if particles were selectively directed to appropriate Sites. n the medical arena, planar gamma scintillation cameras may be employed to study factors affecting such...

  6. Literature Review and Assessment of Plant and Animal Transfer Factors Used in Performance Assessment Modeling

    SciTech Connect

    Robertson, David E.; Cataldo, Dominic A.; Napier, Bruce A.; Krupka, Kenneth M.; Sasser, Lyle B.

    2003-07-20

    A literature review and assessment was conducted by Pacific Northwest National Laboratory (PNNL) to update information on plant and animal radionuclide transfer factors used in performance-assessment modeling. A group of 15 radionuclides was included in this review and assessment. The review is composed of four main sections, not including the Introduction. Section 2.0 provides a review of the critically important issue of physicochemical speciation and geochemistry of the radionuclides in natural soil-water systems as it relates to the bioavailability of the radionuclides. Section 3.0 provides an updated review of the parameters of importance in the uptake of radionuclides by plants, including root uptake via the soil-groundwater system and foliar uptake due to overhead irrigation. Section 3.0 also provides a compilation of concentration ratios (CRs) for soil-to-plant uptake for the 15 selected radionuclides. Section 4.0 provides an updated review on radionuclide uptake data for animal products related to absorption, homeostatic control, approach to equilibration, chemical and physical form, diet, and age. Compiled transfer coefficients are provided for cow’s milk, sheep’s milk, goat’s milk, beef, goat meat, pork, poultry, and eggs. Section 5.0 discusses the use of transfer coefficients in soil, plant, and animal modeling using regulatory models for evaluating radioactive waste disposal or decommissioned sites. Each section makes specific suggestions for future research in its area.

  7. Factors Influencing Assessment Quality in Higher Vocational Education

    ERIC Educational Resources Information Center

    Baartman, Liesbeth; Gulikers, Judith; Dijkstra, Asha

    2013-01-01

    The development of assessments that are fit to assess professional competence in higher vocational education requires a reconsideration of assessment methods, quality criteria and (self)evaluation. This article examines the self-evaluations of nine courses of a large higher vocational education institute. Per course, 4-11 teachers and 3-10…

  8. Airway Gland Structure and Function.

    PubMed

    Widdicombe, Jonathan H; Wine, Jeffrey J

    2015-10-01

    Submucosal glands contribute to airway surface liquid (ASL), a film that protects all airway surfaces. Glandular mucus comprises electrolytes, water, the gel-forming mucin MUC5B, and hundreds of different proteins with diverse protective functions. Gland volume per unit area of mucosal surface correlates positively with impaction rate of inhaled particles. In human main bronchi, the volume of the glands is ∼ 50 times that of surface goblet cells, but the glands diminish in size and frequency distally. ASL and its trapped particles are removed from the airways by mucociliary transport. Airway glands have a tubuloacinar structure, with a single terminal duct, a nonciliated collecting duct, then branching secretory tubules lined with mucous cells and ending in serous acini. They allow for a massive increase in numbers of mucus-producing cells without replacing surface ciliated cells. Active secretion of Cl(-) and HCO3 (-) by serous cells produces most of the fluid of gland secretions. Glands are densely innervated by tonically active, mutually excitatory airway intrinsic neurons. Most gland mucus is secreted constitutively in vivo, with large, transient increases produced by emergency reflex drive from the vagus. Elevations of [cAMP]i and [Ca(2+)]i coordinate electrolyte and macromolecular secretion and probably occur together for baseline activity in vivo, with cholinergic elevation of [Ca(2+)]i being mainly responsive for transient increases in secretion. Altered submucosal gland function contributes to the pathology of all obstructive diseases, but is an early stage of pathogenesis only in cystic fibrosis. PMID:26336032

  9. The Airway Microbiome at Birth

    PubMed Central

    Lal, Charitharth Vivek; Travers, Colm; Aghai, Zubair H.; Eipers, Peter; Jilling, Tamas; Halloran, Brian; Carlo, Waldemar A.; Keeley, Jordan; Rezonzew, Gabriel; Kumar, Ranjit; Morrow, Casey; Bhandari, Vineet; Ambalavanan, Namasivayam

    2016-01-01

    Alterations of pulmonary microbiome have been recognized in multiple respiratory disorders. It is critically important to ascertain if an airway microbiome exists at birth and if so, whether it is associated with subsequent lung disease. We found an established diverse and similar airway microbiome at birth in both preterm and term infants, which was more diverse and different from that of older preterm infants with established chronic lung disease (bronchopulmonary dysplasia). Consistent temporal dysbiotic changes in the airway microbiome were seen from birth to the development of bronchopulmonary dysplasia in extremely preterm infants. Genus Lactobacillus was decreased at birth in infants with chorioamnionitis and in preterm infants who subsequently went on to develop lung disease. Our results, taken together with previous literature indicating a placental and amniotic fluid microbiome, suggest fetal acquisition of an airway microbiome. We speculate that the early airway microbiome may prime the developing pulmonary immune system, and dysbiosis in its development may set the stage for subsequent lung disease. PMID:27488092

  10. The Airway Microbiome at Birth.

    PubMed

    Lal, Charitharth Vivek; Travers, Colm; Aghai, Zubair H; Eipers, Peter; Jilling, Tamas; Halloran, Brian; Carlo, Waldemar A; Keeley, Jordan; Rezonzew, Gabriel; Kumar, Ranjit; Morrow, Casey; Bhandari, Vineet; Ambalavanan, Namasivayam

    2016-01-01

    Alterations of pulmonary microbiome have been recognized in multiple respiratory disorders. It is critically important to ascertain if an airway microbiome exists at birth and if so, whether it is associated with subsequent lung disease. We found an established diverse and similar airway microbiome at birth in both preterm and term infants, which was more diverse and different from that of older preterm infants with established chronic lung disease (bronchopulmonary dysplasia). Consistent temporal dysbiotic changes in the airway microbiome were seen from birth to the development of bronchopulmonary dysplasia in extremely preterm infants. Genus Lactobacillus was decreased at birth in infants with chorioamnionitis and in preterm infants who subsequently went on to develop lung disease. Our results, taken together with previous literature indicating a placental and amniotic fluid microbiome, suggest fetal acquisition of an airway microbiome. We speculate that the early airway microbiome may prime the developing pulmonary immune system, and dysbiosis in its development may set the stage for subsequent lung disease. PMID:27488092

  11. Nonmicrobial-mediated inflammatory airway diseases--an update.

    PubMed

    Ramesh Babu, Polani B; Krishnamoorthy, P

    2014-03-01

    In lungs, airways are in constant contact with air, microbes, allergens, and environmental pollutants. The airway epithelium represents the first line of lung defense through different mechanisms, which facilitate clearance of inhaled pathogens and environmental particles while minimizing an inflammatory response. The innate immune system facilitates immediate recognition of both foreign pathogens and tissue damage through toll-like receptor, which acts as a gateway for all intracellular events leading to inflammation. In the absence of microbial stimulus, the immune system is capable of detecting a wide range of insults against the host. This review focuses on various molecular mechanisms involved in pathophysiology of airway inflammation mediated by environmental factors, cellular stress, and pharmacological and clinical agents. PMID:24293217

  12. Airway microbiota and acute respiratory infection in children.

    PubMed

    Hasegawa, Kohei; Camargo, Carlos A

    2015-01-01

    Acute respiratory infections (ARIs), such as bronchiolitis and pneumonia, are the leading cause of hospitalization of infants in the US. While the incidence and severity of ARI can vary widely among children, the reasons for these differences are not fully explained by traditional risk factors (e.g., prematurity, viral pathogens). The recent advent of molecular diagnostic techniques has revealed the presence of highly functional communities of microbes inhabiting the human body (i.e., microbiota) that appear to influence development of local and systemic immune response. We propose a 'risk and resilience' model in which airway microbiota are associated with an increased (risk microbiota) or decreased (resilience microbiota) incidence and severity of ARI in children. We also propose that modulating airway microbiota (e.g., from risk to resilience microbiota) during early childhood will optimize airway immunity and, thereby, decrease ARI incidence and severity in children. PMID:25961472

  13. Teleoperator hand controllers: A contextual human factors assessment

    SciTech Connect

    Draper, J.V.

    1994-05-01

    This document provides a human factors assessment of controllers for use with remotely controlled manipulators deployed to remove hazardous waste from underground storage tanks. The analysis concentrates on controller technique (i.e., the broad class of hand controller) and not on details of controller ergonomics. Examples of controller techniques include, for example, direct rate control, resolved unilateral position control, and direct bilateral position control. Using an existing concept, the Tank Waste Retrieval Manipulator System, as a reference, two basic types of manipulators may be identified for this application. A long reach, gross-positioning manipulator (LRM) may be used to position a smaller manipulator or an end-effector within a work site. For a Long Reach Manipulator, which will have an enormous motion range and be capable of high end-effector velocity, it will be safest and most efficient to use a resolved rate control system. A smaller, dexterous manipulator may be used to perform handling work within a relatively small work site, (i.e., to complete tasks requiring near-human dexterity). For a Dexterous Manipulator, which will have a smaller motion range than the LRM and be required to perform more difficult tasks, a resolved bilateral position control system will be safest and most efficient. However, during some waste recovery tasks it may be important to support the users by restricting movements to a single plane or axis. This can be done with a resolved bilateral position control system by (1) using the master controller force output to restrict controller inputs or (2) switching the controller to a multiaxis rate control mode and using the force output to provide a spring return to center functionality.

  14. Assessment of epidermal growth factor receptor status in glioblastomas

    PubMed Central

    Zhu, Hui-Jun; Ogawa, Mikako; Magata, Yasuhiro; Hirata, Masahiko; Ohmomo, Yoshiro; Namba, Hiroki; Sakahara, Harumi

    2013-01-01

    Objective(s): Our previous study showed that a newly designed tracer radioiodinated 6-(3-morpholinopropoxy)-7-ethoxy-4-(3’-iodophenoxy)quinazoline ([125I]PYK) is promising for the evaluation of the epidermal growth factor receptor (EGFR) status and prediction of gefitinib treatment of non-small cell lung cancer. EGFR is over-expressed and mutated also in glioblastoma. In the present study, the expressions and mutation of EGFR were tested with [125I] PYK in glioblastoma in vitro and in vivo to determine whether this could be used to predict the sensitivity of glioblastoma to gefitinib treatment. Methods: Glioblastoma cell lines with different expression of EGFR were tested. Growth inhibition of cell lines by gefitinib was assessed by the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) colorimetric assay. Uptake levels of [125I]PYK were evaluated in cell lines in vitro. Tumor targeting of [125I]PYK was examined by a biodistribution study and imaging by single photon emission computed tomography (SPECT). Results: High concentrations of gefitinib were needed to suppress EGFR-mediated proliferation. The uptake of [125I] PYK in cell lines in vitro was low, and showed no correlation with EGFR expression or mutation status. Biodistribution study and SPECT imaging with [125I]PYK for xenografts showed no [125I]PYK uptake. Conclusion: The results showed prediction of gefitinib effectiveness was difficult in glioblastoma by [125I]PYK, which might be due to the complicated expression of EGFR status in glioblastoma. Thus, new tracers for sites downstream of the mutant EGFR should be investigated in further studies.

  15. AIRWAY IDENTIFICATION WITHIN PLANAR GAMMA CAMERA IMAGES USING COMPUTER MODELS OF LUNG MORPHOLOGY

    EPA Science Inventory

    The quantification of inhaled aerosols could be improved if a more comprehensive assessment of their spatial distribution patterns among lung airways were obtained. A common technique for quantifying particle deposition in human lungs is with planar gamma scintigraphy. However, t...

  16. Factors in International Space Station Integration Feasibility Assessments

    NASA Technical Reports Server (NTRS)

    Watson, Patricia M.; Dunn, James

    2002-01-01

    The International Space Station, ISS, is a growing vehicle. The ISS configuration changes internally and externally with each ISS flight. Each flight adds resources and capabilities such as docking/berthing ports, power, stowage volume, heat rejection, and data processing capability. The configuration, capabilities and performance characteristics of the vehicle will be in flux until assembly complete. At the same time the knowledge about what is required to support humans involved in long duration space flight is also being greatly expanded. In addition to the changes occurring on-orbit, the situation on the ground is also very dynamic. Proposals for new ISS elements, proposed deletions of elements, changes to the ISS requirements, and changes to the planned configuration are always under evaluation. Furthermore, budgetary issues have driven the need to explore alternative options for the ISS . This environment has made the role of the technical integrator in the ISS program unique in that the baseline against which proposals are evaluated is always changing. The nature of the International Space Station Program adds another dimension to the integrators task. ISS program activities are spread across several centers: KSC, MSFC, GRC, DFRC, ARC and JSc. There are six International Partners/participants each with their own unique organizations. The prime contractor is in Texas, California and Alabama. And, the Space Shuttle Program as the launch vehicle provider is another major interface. In spite of the fluidity of the technical baseline, projections and organizational complexity, in the course of evaluating proposals and producing feasibility assessments there are factors, which frequently emerge as significant. These factors tend to be the limiting conditions when they come into play. The finite resources, which tend to limit the options for ISS are: upmass, life support and crew rescue capability, crew time, utilities, exercise equipment, and docking

  17. c-Myc regulates proliferation and Fgf10 expression in airway smooth muscle after airway epithelial injury in mouse.

    PubMed

    Volckaert, Thomas; Campbell, Alice; De Langhe, Stijn

    2013-01-01

    During lung development, Fibroblast growth factor 10 (Fgf10), which is expressed in the distal mesenchyme and regulated by Wnt signaling, acts on the distal epithelial progenitors to maintain them and prevent them from differentiating into proximal (airway) epithelial cells. Fgf10-expressing cells in the distal mesenchyme are progenitors for parabronchial smooth muscle cells (PSMCs). After naphthalene, ozone or bleomycin-induced airway epithelial injury, surviving epithelial cells secrete Wnt7b which then activates the PSMC niche to induce Fgf10 expression. This Fgf10 secreted by the niche then acts on a subset of Clara stem cells to break quiescence, induce proliferation and initiate epithelial repair. Here we show that conditional deletion of the Wnt target gene c-Myc from the lung mesenchyme during development does not affect proper epithelial or mesenchymal differentiation. However, in the adult lung we show that after naphthalene-mediated airway epithelial injury c-Myc is important for the activation of the PSMC niche and as such induces proliferation and Fgf10 expression in PSMCs. Our data indicate that conditional deletion of c-Myc from PSMCs inhibits airway epithelial repair, whereas c-Myc ablation from Clara cells has no effect on airway epithelial regeneration. These findings may have important implications for understanding the misregulation of lung repair in asthma and COPD. PMID:23967208

  18. [Orthodontics and the upper airway].

    PubMed

    Cobo Plana, J; de Carlos Villafranca, F; Macías Escalada, E

    2004-03-01

    One of the general aims of orthodontic treatment and of the combination of orthodontics and orthognathic surgery is to achieve good occlusion and aesthetic improvement, especially in cases of severe dentoskeletal deformities. However, on many occasions, the parameters of the upper airways are not taken into account when the aims of conventional treatment are fulfilled. Patients with obstructive alterations during sleep represent for the orthodontist a type of patient who differs from the normal; for them, treatment should include the objective of improving oxygen saturation. Here, functional considerations should outweigh purely aesthetic ones. It is important, when making an orthodontic, surgical or combined diagnosis for a patient, to bear in mind the impact that treatment may have on the upper airways. Good aesthetics should never be achieved for some of our patients at the expense of diminishing the capacity of their upper airways. PMID:15301356

  19. Increased airway reactivity in a neonatal mouse model of Continuous Positive Airway Pressure (CPAP)

    PubMed Central

    Mayer, Catherine A.; Martin, Richard J.; MacFarlane, Peter M.

    2015-01-01

    Background Continuous positive airway pressure (CPAP) is a primary form of respiratory support used in the intensive care of preterm infants, but its long-term effects on airway (AW) function are unknown. Methods We developed a neonatal mouse model of CPAP treatment to determine whether it modifies later AW reactivity. Un-anesthetized spontaneously breathing mice were fitted with a mask to deliver CPAP (6cmH2O, 3hrs/day) for 7 consecutive days starting at postnatal day 1. Airway reactivity to methacholine was assessed using the in vitro living lung slice preparation. Results One week of CPAP increased AW responsiveness to methacholine in male, but not female mice, compared to untreated control animals. The AW hyper-reactivity of male mice persisted for 2 weeks (at P21) after CPAP treatment ended. 4 days of CPAP, however, did not significantly increase AW reactivity. Females also exhibited AW hyper-reactivity at P21, suggesting a delayed response to early (7 days) CPAP treatment. The effects of 7 days of CPAP on hyper-reactivity to methacholine were unique to smaller AWs whereas larger ones were relatively unaffected. Conclusion These data may be important to our understanding of the potential long-term consequences of neonatal CPAP therapy used in the intensive care of preterm infants. PMID:25950451

  20. Molecular Mechanisms of Airway Hyperresponsiveness in a Murine Model of Steroid-Resistant Airway Inflammation.

    PubMed

    Manni, Michelle L; Mandalapu, Sivanarayana; McHugh, Kevin J; Elloso, M Merle; Dudas, Paul L; Alcorn, John F

    2016-02-01

    IL-13 and IL-17A, produced mainly by Th2 and Th17 cells, respectively, have an influential role in asthma pathogenesis. We examined the role of IL-13 and IL-17A in mediating airway hyperresponsiveness (AHR), lung inflammation, and mucus metaplasia in a dual Th2/Th17 model of asthma. IL-13 and/or IL-17A were neutralized using mAbs. Th2/Th17 adoptive transfer induced a mixed asthma phenotype characterized by elevated eosinophilia and neutrophilia, tissue inflammation, mucus metaplasia, and AHR that were partially reversible with steroid treatment. Pulmonary inflammation and quasi-static lung compliance were largely unaffected by neutralization of IL-13 and/or IL-17A. However, neutralization of IL-13 alone or in combination with IL-17A significantly attenuated AHR and mucus metaplasia. Further, STAT6 activation was attenuated following IL-13 and IL-13/IL-17A Ab treatment. We next assessed the role of STAT6 in Th2/Th17-mediated allergic airway disease using STAT6(-/-) mice. STAT6(-/-) mice adoptively transferred with Th2/Th17 cells had decreased AHR compared with controls. These data suggest that IL-13 drives AHR and mucus metaplasia in a STAT6-dependent manner, without directly contributing to airway or tissue inflammation. IL-17A independently contributes to AHR, but it only partially mediates inflammation and mucus metaplasia in a mixed Th2/Th17 model of steroid-resistant asthma. PMID:26729801

  1. Noninvasive ventilation and the upper airway: should we pay more attention?

    PubMed

    Oppersma, Eline; Doorduin, Jonne; van der Heijden, Erik H F M; van der Hoeven, Johannes G; Heunks, Leo M A

    2013-01-01

    In an effort to reduce the complications related to invasive ventilation, the use of noninvasive ventilation (NIV) has increased over the last years in patients with acute respiratory failure. However, failure rates for NIV remain high in specific patient categories. Several studies have identified factors that contribute to NIV failure, including low experience of the medical team and patient-ventilator asynchrony. An important difference between invasive ventilation and NIV is the role of the upper airway. During invasive ventilation the endotracheal tube bypasses the upper airway, but during NIV upper airway patency may play a role in the successful application of NIV. In response to positive pressure, upper airway patency may decrease and therefore impair minute ventilation. This paper aims to discuss the effect of positive pressure ventilation on upper airway patency and its possible clinical implications, and to stimulate research in this field. PMID:24314000

  2. Noninvasive ventilation and the upper airway: should we pay more attention?

    PubMed Central

    2013-01-01

    In an effort to reduce the complications related to invasive ventilation, the use of noninvasive ventilation (NIV) has increased over the last years in patients with acute respiratory failure. However, failure rates for NIV remain high in specific patient categories. Several studies have identified factors that contribute to NIV failure, including low experience of the medical team and patient–ventilator asynchrony. An important difference between invasive ventilation and NIV is the role of the upper airway. During invasive ventilation the endotracheal tube bypasses the upper airway, but during NIV upper airway patency may play a role in the successful application of NIV. In response to positive pressure, upper airway patency may decrease and therefore impair minute ventilation. This paper aims to discuss the effect of positive pressure ventilation on upper airway patency and its possible clinical implications, and to stimulate research in this field. PMID:24314000

  3. Emphysema- and airway-dominant COPD phenotypes defined by standardised quantitative computed tomography.

    PubMed

    Subramanian, Deepak R; Gupta, Sumit; Burggraf, Dorothe; Vom Silberberg, Suzan J; Heimbeck, Irene; Heiss-Neumann, Marion S; Haeussinger, Karl; Newby, Chris; Hargadon, Beverley; Raj, Vimal; Singh, Dave; Kolsum, Umme; Hofer, Thomas P; Al-Shair, Khaled; Luetzen, Niklas; Prasse, Antje; Müller-Quernheim, Joachim; Benea, Giorgio; Leprotti, Stefano; Boschetto, Piera; Gorecka, Dorota; Nowinski, Adam; Oniszh, Karina; Castell, Wolfgang Zu; Hagen, Michael; Barta, Imre; Döme, Balázs; Strausz, Janos; Greulich, Timm; Vogelmeier, Claus; Koczulla, Andreas R; Gut, Ivo; Hohlfeld, Jens; Welte, Tobias; Lavae-Mokhtari, Mahyar; Ziegler-Heitbrock, Loems; Brightling, Christopher; Parr, David G

    2016-07-01

    EvA (Emphysema versus Airway disease) is a multicentre project to study mechanisms and identify biomarkers of emphysema and airway disease in chronic obstructive pulmonary disease (COPD). The objective of this study was to delineate objectively imaging-based emphysema-dominant and airway disease-dominant phenotypes using quantitative computed tomography (QCT) indices, standardised with a novel phantom-based approach.441 subjects with COPD (Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages 1-3) were assessed in terms of clinical and physiological measurements, laboratory testing and standardised QCT indices of emphysema and airway wall geometry.QCT indices were influenced by scanner non-conformity, but standardisation significantly reduced variability (p<0.001) and led to more robust phenotypes. Four imaging-derived phenotypes were identified, reflecting "emphysema-dominant", "airway disease-dominant", "mixed" disease and "mild" disease. The emphysema-dominant group had significantly higher lung volumes, lower gas transfer coefficient, lower oxygen (PO2 ) and carbon dioxide (PCO2 ) tensions, higher haemoglobin and higher blood leukocyte numbers than the airway disease-dominant group.The utility of QCT for phenotyping in the setting of an international multicentre study is improved by standardisation. QCT indices of emphysema and airway disease can delineate within a population of patients with COPD, phenotypic groups that have typical clinical features known to be associated with emphysema-dominant and airway-dominant disease. PMID:27230444

  4. Sex differences in the development of airway epithelial tolerance to naphthalene

    PubMed Central

    Sutherland, K. M.; Edwards, P. C.; Combs, T. J.

    2012-01-01

    Exposure to air pollution has been linked to pulmonary diseases. Naphthalene (NA), an abundant polycyclic aromatic hydrocarbon in tobacco smoke and urban air, is a model toxicant for air pollution effects in the lung. Repeated exposures to NA in male mice result in tolerance, defined as the emergence of a resistant cell phenotype after prior exposure. Tolerance has not been studied in females. Females have sex differences in airway epithelial responses and in the prevalence of certain airway diseases. Male and female mice were exposed to a tolerance-inducing regimen of NA, and lungs were examined by airway level to characterize the cellular changes associated with repeated NA exposure and to assess the expression of genes and proteins involved in NA bioactivation and detoxification. The airway epithelium in treated males resembled that of controls. Females in the tolerant state were characterized by dense populations of ciliated cells in midlevel, distal, and bifurcating airways and a lower abundance of Clara cells at all airway levels. Cytotoxicity following a secondary challenge dose was also greater in females than males. Furthermore, females had decreased gene/protein expression of CYP2F2, a P-450 that metabolizes NA to a toxic epoxide, and glutamate-cysteine ligase, the rate-limiting enzyme in glutathione synthesis, than NA-tolerant males at all airway levels examined. We conclude that, while females develop tolerance, sex differences exist in the tolerant state by airway level, and females remain more susceptible than males to repeated exposures to NA. PMID:22003090

  5. Kinematic MRI study of upper-airway biomechanics using electrical muscle stimulation

    NASA Astrophysics Data System (ADS)

    Brennick, Michael J.; Margulies, Susan S.; Ford, John C.; Gefter, Warren B.; Pack, Allan I.

    1997-05-01

    We have developed a new and powerful method to study the movement and function of upper airway muscles. Our method is to use direct electrical stimulation of individual upper airway muscles, while performing state of the art high resolution magnetic resonance imaging (MRI). We have adapted a paralyzed isolated UA cat model so that positive or negative static pressure in the UA can be controlled at specific levels while electrical muscle stimulation is applied during MRI. With these techniques we can assess the effect of muscle stimulation on airway cross-sectional area compliance and soft tissue motion. We are reporting the preliminary results and MRI techniques which have enabled us to examine changes in airway dimensions which result form electrical stimulation of specific upper airway dilator muscles. The results of this study will be relevant to the development of new clinical treatments for obstructive sleep apnea by providing new information as to exactly how upper airway muscles function to dilate the upper airway and the strength of stimulation required to prevent the airway obstruction when overall muscle tone may not be sufficient to maintain regular breathing.

  6. A system to generate simultaneous forced oscillation and continuous positive airway pressure.

    PubMed

    Farré, R; Rotger, M; Montserrat, J M; Navajas, D

    1997-06-01

    Assessment of airway obstruction in patients with obstructive sleep apnoea (OSA) subjected to continuous positive airway pressure (CPAP) may be carried out using the forced oscillation technique (FOT). To facilitate routine application of forced oscillation (FO) in sleep studies, our aim was to design a system capable of generating CPAP and applying FOT simultaneously. We constructed a prototype CPAP + FO generator by connecting a specially designed electromagnetic valve in parallel with a conventional blower. The capacity of the prototype to generate forced oscillation (5 Hz +/- 1 hPa) was tested by connecting it to a model simulating spontaneous breathing. The response of the prototype for target CPAPs of 5, 10 and 15 hPa and imposed sinusoidal breathing with peak flow up to 0.75 L x s(-1) was excellent when compared with that reported for commercially available CPAP generators. The applicability of the prototype was tested by applying it to assess airway obstruction in four patients with OSA during sleep. We conclude that the generator designed is able to apply continuous positive airway pressure and forced oscillation simultaneously. The system could be useful for automatic and noninvasive assessment of airway obstruction in patients with obstructive sleep apnoea subjected to continuous positive airway pressure. Future development of the generator may be helpful in implementing a set-up for automatic titration of continuous positive airway pressure. PMID:9192942

  7. 21 CFR 868.5810 - Airway connector.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Airway connector. 868.5810 Section 868.5810 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5810 Airway connector. (a) Identification. An airway connector is a device intended to...

  8. Chronic effects of mechanical force on airways.

    PubMed

    Tschumperlin, Daniel J; Drazen, Jeffrey M

    2006-01-01

    Airways are embedded in the mechanically dynamic environment of the lung. In utero, this mechanical environment is defined largely by fluid secretion into the developing airway lumen. Clinical, whole lung, and cellular studies demonstrate pivotal roles for mechanical distention in airway morphogenesis and cellular behavior during lung development. In the adult lung, the mechanical environment is defined by a dynamic balance of surface, tissue, and muscle forces. Diseases of the airways modulate both the mechanical stresses to which the airways are exposed as well as the structure and mechanical behavior of the airways. For instance, in asthma, activation of airway smooth muscle abruptly changes the airway size and stress state within the airway wall; asthma also results in profound remodeling of the airway wall. Data now demonstrate that airway epithelial cells, smooth muscle cells, and fibroblasts respond to their mechanical environment. A prominent role has been identified for the epithelium in transducing mechanical stresses, and in both the fetal and mature airways, epithelial cells interact with mesenchymal cells to coordinate remodeling of tissue architecture in response to the mechanical environment. PMID:16460284

  9. Site of Fluid Secretion in Small Airways.

    PubMed

    Flores-Delgado, Guillermo; Lytle, Christian; Quinton, Paul M

    2016-03-01

    The secretion and management of readily transportable airway surface liquid (ASL) along the respiratory tract is crucial for the clearance of debris and pathogens from the lungs. In proximal large airways, submucosal glands (SMGs) can produce ASL. However, in distal small airways, SMGs are absent, although the lumens of these airways are, uniquely, highly plicated. Little is known about the production and maintenance of ASL in small airways, but using electrophysiology, we recently found that native porcine small airways simultaneously secrete and absorb. How these airways can concurrently transport ASL in opposite directions is puzzling. Using high expression of the Na-K-2Cl cotransport (NKCC) 1 protein (SLC12a2) as a phenotypic marker for fluid secretory cells, immunofluorescence microscopy of porcine small airways revealed two morphologically separated sets of luminal epithelial cells. NKCC1 was abundantly expressed by most cells in the contraluminal regions of the pleats but highly expressed very infrequently by cells in the luminal folds of the epithelial plications. In larger proximal airways, the acini of SMGs expressed NKCC1 prominently, but cells expressing NKCC1 in the surface epithelium were sparse. Our findings indicate that, in the small airway, cells in the pleats of the epithelium secrete ASL, whereas, in the larger proximal airways, SMGs mainly secrete ASL. We propose a mechanism in which the locations of secretory cells in the base of pleats and of absorptive cells in luminal folds physically help maintain a constant volume of ASL in small airways. PMID:26562629

  10. Validation of an enhanced knowledge-based method for segmentation and quantitative analysis of intrathoracic airway trees from three-dimensional CT images

    SciTech Connect

    Sonka, M.; Park, W.; Hoffman, E.A.

    1995-12-31

    Accurate assessment of airway physiology, evaluated in terms of geometric changes, is critically dependent upon the accurate imaging and image segmentation of the three-dimensional airway tree structure. The authors have previously reported a knowledge-based method for three-dimensional airway tree segmentation from high resolution CT (HRCT) images. Here, they report a substantially improved version of the method. In the current implementation, the method consists of several stages. First, the lung borders are automatically determined in the three-dimensional set of HRCT data. The primary airway tree is semi-automatically identified. In the next stage, potential airways are determined in individual CT slices using a rule-based system that uses contextual information and a priori knowledge about pulmonary anatomy. Using three-dimensional connectivity properties of the pulmonary airway tree, the three-dimensional tree is constructed from the set of adjacent slices. The method`s performance and accuracy were assessed in five 3D HRCT canine images. Computer-identified airways matched 226/258 observer-defined airways (87.6%); the computer method failed to detect the airways in the remaining 32 locations. By visual assessment of rendered airway trees, the experienced observers judged the computer-detected airway trees as highly realistic.

  11. Computer-aided analysis of airway trees in micro-CT scans of ex vivo porcine lung tissue.

    PubMed

    Bauer, Christian; Adam, Ryan; Stoltz, David A; Beichel, Reinhard R

    2012-12-01

    We present a highly automated approach to obtain detailed structural models of airway trees from ex vivo porcine lung tissue imaged with a high resolution micro-CT scanner. Such information is an important prerequisite to systematically study models of lung disease that affect airway morphology. The method initially identifies all tubular airway-like structures in the lung. In a second processing step, these structures are grouped into a connected airway tree by utilizing prior knowledge about the airway trees branching pattern. The method was evaluated on 12 micro-CT scans from four tracheal lobes of piglets imaged at three different inflation levels. For this study, two control piglets and two cystic fibrosis piglets were used. For systematic validation of our approach, an airway nomenclature was developed for the pig airway tree. Out of more than 3500 airway tree segments assessed during evaluation, 88.45% were correctly identified by the method. No false positive airway branches were found. A detailed performance analysis for different airway tree hierarchy levels, lung inflation levels and piglets with/without cystic fibrosis is presented in the paper. PMID:22959430

  12. Laryngeal mask airway: an alternative for the difficult airway.

    PubMed

    Jones, J R

    1995-10-01

    The laryngeal mask airway (LMA) was invented by Dr. Archie Brain at the London Hospital, Whitechapel, in 1981. Dr. Brain's main objective for the LMA was that it would provide a better method of maintaining a patient's airway than by face mask. Also, the LMA would be less hemodynamically stressful than with insertion of an endotracheal tube. The LMA consists of a silicone rubber tube connected to a miniature silicone mask. The perimeter of the mask consists of an inflatable elliptical cuff, which forms a tip at the distal aspect of the LMA. The aperture bars in the dome of the mask lift the epiglottis away, so the lumen remains unobstructive. The LMA forms a low pressure seal around the larynx. The LMA is contraindicated in any situation where the patient is at risk for pulmonary aspiration. The LMA is not a substitute for a properly placed endotracheal tube in this situation. The American Society of Anesthesiologists' difficult airway algorithm recommends the insertion of an LMA when ventilation and/or intubation are difficult. The distal aperture of the LMA is in close approximation to the vocal cords, so a 6.0-mm internal diameter endotracheal tube can be passed over an intubating stylet or a pediatric fiberoptic bronchoscope to secure a patient's airway. PMID:7502644

  13. Supra-Epiglottic Upper Airway Volume in Elderly Patients with Obstructive Sleep Apnea Hypopnea Syndrome

    PubMed Central

    Abdirahman Mohamed Moussa, Syad; Celle, Sébastien; Laurent, Bernard; Barthélémy, Jean-Claude; Barral, Fabrice-Guy; Roche, Frédéric

    2016-01-01

    Objective Small upper airway measurements areas and high body mass index are recognized risk factors for obstructive sleep apnea syndrome (OSAS) in non-elderly populations; however, there is limited information regarding elderly patients. We evaluated whether upper airway volume is associated with OSAS and OSAS treated with continuous positive airway pressure (CPAP) treatment and whether BMI is correlated with upper airway volume and measurements in elderly subjects. Methods In 60 volunteers aged 75.58±0.9 years: 20 OSAS, 20 OSAS chronically treated with CPAP, and 20 controls, semi-automatic segmentation, retropalatal distance and transverse diameter of the supra-epiglottic upper airway were evaluated using 3DT1-weighted magnetic resonance imaging. Anteroposterior to transverse diameter ratio was defined as retropalatar diameter/transverse diameter. Results There were no significant differences in supra-epiglottic upper airway volume between OSAS, CPAP treated patients, and controls. There were significant differences in retropalatal distance and anteroposterior to transverse diameter ratio between OSAS, CPAP treated patients, and controls (P = 0.008 and P<0.0001 respectively). There was a significant correlation between body mass index and retropalatal distance (P<0.05) but not with supra-epiglottic upper airway volume. Conclusion In elderly subjects, OSAS and body mass index are not associated with changes in supra-epiglottic upper airway volume but are associated with modification of pharynx shape. PMID:27336305

  14. Airway Surface Dehydration Aggravates Cigarette Smoke-Induced Hallmarks of COPD in Mice

    PubMed Central

    Seys, Leen J. M.; Verhamme, Fien M.; Dupont, Lisa L.; Desauter, Elke; Duerr, Julia; Seyhan Agircan, Ayca; Conickx, Griet; Joos, Guy F.; Brusselle, Guy G.

    2015-01-01

    Introduction Airway surface dehydration, caused by an imbalance between secretion and absorption of ions and fluid across the epithelium and/or increased epithelial mucin secretion, impairs mucociliary clearance. Recent evidence suggests that this mechanism may be implicated in chronic obstructive pulmonary disease (COPD). However, the role of airway surface dehydration in the pathogenesis of cigarette smoke (CS)-induced COPD remains unknown. Objective We aimed to investigate in vivo the effect of airway surface dehydration on several CS-induced hallmarks of COPD in mice with airway-specific overexpression of the β-subunit of the epithelial Na+ channel (βENaC). Methods βENaC-Tg mice and wild-type (WT) littermates were exposed to air or CS for 4 or 8 weeks. Pathological hallmarks of COPD, including goblet cell metaplasia, mucin expression, pulmonary inflammation, lymphoid follicles, emphysema and airway wall remodelling were determined and lung function was measured. Results Airway surface dehydration in βENaC-Tg mice aggravated CS-induced airway inflammation, mucin expression and destruction of alveolar walls and accelerated the formation of pulmonary lymphoid follicles. Moreover, lung function measurements demonstrated an increased compliance and total lung capacity and a lower resistance and hysteresis in βENaC-Tg mice, compared to WT mice. CS exposure further altered lung function measurements. Conclusions We conclude that airway surface dehydration is a risk factor that aggravates CS-induced hallmarks of COPD. PMID:26066648

  15. Epithelium-generated neuropeptide Y induces smooth muscle contraction to promote airway hyperresponsiveness.

    PubMed

    Li, Shanru; Koziol-White, Cynthia; Jude, Joseph; Jiang, Meiqi; Zhao, Hengjiang; Cao, Gaoyuan; Yoo, Edwin; Jester, William; Morley, Michael P; Zhou, Su; Wang, Yi; Lu, Min Min; Panettieri, Reynold A; Morrisey, Edward E

    2016-05-01

    Asthma is one of the most common chronic diseases globally and can be divided into presenting with or without an immune response. Current therapies have little effect on nonimmune disease, and the mechanisms that drive this type of asthma are poorly understood. Here, we have shown that loss of the transcription factors forkhead box P1 (Foxp1) and Foxp4, which are critical for lung epithelial development, in the adult airway epithelium evokes a non-Th2 asthma phenotype that is characterized by airway hyperresponsiveness (AHR) without eosinophilic inflammation. Transcriptome analysis revealed that loss of Foxp1 and Foxp4 expression induces ectopic expression of neuropeptide Y (Npy), which has been reported to be present in the airways of asthma patients, but whose importance in disease pathogenesis remains unclear. Treatment of human lung airway explants with recombinant NPY increased airway contractility. Conversely, loss of Npy in Foxp1- and Foxp4-mutant airway epithelium rescued the AHR phenotype. We determined that NPY promotes AHR through the induction of Rho kinase activity and phosphorylation of myosin light chain, which induces airway smooth muscle contraction. Together, these studies highlight the importance of paracrine signals from the airway epithelium to the underlying smooth muscle to induce AHR and suggest that therapies targeting epithelial induction of this phenotype may prove useful in treatment of noneosinophilic asthma. PMID:27088802

  16. Histone deacetylase inhibitors suppress RSV infection and alleviate virus-induced airway inflammation.

    PubMed

    Feng, Qiuqin; Su, Zhonglan; Song, Shiyu; Χu, Hui; Zhang, Bin; Yi, Long; Tian, Man; Wang, Hongwei

    2016-09-01

    Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in infants and young children. However, the majority of RSV-infected patients only show mild symptoms. Different severities of infection and responses among the RSV-infected population indicate that epigenetic regulation as well as personal genetic background may affect RSV infectivity. Histone deacetylase (HDAC) is an important epigenetic regulator in lung diseases. The present study aimed to explore the possible connection between HDAC expression and RSV-induced lung inflammation. To address this question, RSV-infected airway epithelial cells (BEAS‑2B) were prepared and a mouse model of RSV infection was established, and then treated with various concentrations of HDAC inhibitors (HDACis), namely trichostatin A (TSA) and suberoylanilide hydroxamic acid (SAHA). Viral replication and markers of virus-induced airway inflammation or oxidative stress were assessed. The activation of the nuclear factor-κB (NF-κB), cyclo-oxygenase-2 (COX-2), mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription 3 (STAT3) signaling pathways was evaluated by western blot analysis. Our results showed that RSV infection in airway epithelial cells (AECs) significantly decreased histone acetylation levels by altering HDAC2 expression. The treatment of RSV-infected AECs with HDACis significantly restricted RSV replication by upregulating the interferon-α (IFN-α) related signaling pathways. The treatment of RSV-infected AECs with HDACis also significantly inhibited RSV-induced pro-inflammatory cytokine release [interleukin (IL)-6 and IL-8] and oxidative stress-related molecule production [malondialdehyde (MDA), and nitrogen monoxide (NO)]. The activation of NF-κB, COX-2, MAPK and Stat3, which orchestrate pro‑inflammatory gene expression and oxidative stress injury, was also significantly inhibited. Our in vivo study using a mouse model of

  17. Histone deacetylase inhibitors suppress RSV infection and alleviate virus-induced airway inflammation

    PubMed Central

    Feng, Qiuqin; Su, Zhonglan; Song, Shiyu; Xu, Hui; Zhang, Bin; Yi, Long; Tian, Man; Wang, Hongwei

    2016-01-01

    Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in infants and young children. However, the majority of RSV-infected patients only show mild symptoms. Different severities of infection and responses among the RSV-infected population indicate that epigenetic regulation as well as personal genetic background may affect RSV infectivity. Histone deacetylase (HDAC) is an important epigenetic regulator in lung diseases. The present study aimed to explore the possible connection between HDAC expression and RSV-induced lung inflammation. To address this question, RSV-infected airway epithelial cells (BEAS-2B) were prepared and a mouse model of RSV infection was established, and then treated with various concentrations of HDAC inhibitors (HDACis), namely trichostatin A (TSA) and suberoylanilide hydroxamic acid (SAHA). Viral replication and markers of virus-induced airway inflammation or oxidative stress were assessed. The activation of the nuclear factor-κB (NF-κB), cyclo-oxygenase-2 (COX-2), mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription 3 (STAT3) signaling pathways was evaluated by western blot analysis. Our results showed that RSV infection in airway epithelial cells (AECs) significantly decreased histone acetylation levels by altering HDAC2 expression. The treatment of RSV-infected AECs with HDACis significantly restricted RSV replication by upregulating the interferon-α (IFN-α) related signaling pathways. The treatment of RSV-infected AECs with HDACis also significantly inhibited RSV-induced pro-inflammatory cytokine release [interleukin (IL)-6 and IL-8] and oxidative stress-related molecule production [malondialdehyde (MDA), and nitrogen monoxide (NO)]. The activation of NF-κB, COX-2, MAPK and Stat3, which orchestrate pro-inflammatory gene expression and oxidative stress injury, was also significantly inhibited. Our in vivo study using a mouse model of RSV infection

  18. Investigating Factors Affecting the Uptake of Automated Assessment Technology

    ERIC Educational Resources Information Center

    Dreher, Carl; Reiners, Torsten; Dreher, Heinz

    2011-01-01

    Automated assessment is an emerging innovation in educational praxis, however its pedagogical potential is not fully utilised in Australia, particularly regarding automated essay grading. The rationale for this research is that the usage of automated assessment currently lags behind the capacity that the technology provides, thus restricting the…

  19. How the airway smooth muscle in cystic fibrosis reacts in proinflammatory conditions: implications for airway hyper-responsiveness and asthma in cystic fibrosis.

    PubMed

    McCuaig, Sarah; Martin, James G

    2013-04-01

    Among patients with cystic fibrosis there is a high prevalence (40-70%) of asthma signs and symptoms such as cough and wheezing and airway hyper-responsiveness to inhaled histamine or methacholine. Whether these abnormal airway responses are due to a primary deficiency in the cystic fibrosis transmembrane conductance regulator (CFTR) or are secondary to the inflammatory environment in the cystic fibrosis lungs is not clear. A role for the CFTR in smooth muscle function is emerging, and alterations in contractile signalling have been reported in CFTR-deficient airway smooth muscle. Persistent bacterial infection, especially with Pseudomonas aeruginosa, stimulates interleukin-8 release from the airway epithelium, resulting in neutrophilic inflammation. Increased neutrophilia and skewing of CFTR-deficient T-helper cells to type 2 helper T cells creates an inflammatory environment characterised by high concentrations of tumour necrosis factor α, interleukin-8, and interleukin-13, which might all contribute to increased contractility of airway smooth muscle in cystic fibrosis. An emerging role of interleukin-17, which is raised in patients with cystic fibrosis, in airway smooth muscle proliferation and hyper-responsiveness is apparent. Increased understanding of the molecular mechanisms responsible for the altered smooth muscle physiology in patients with cystic fibrosis might provide insight into airway dysfunction in this disease. PMID:24429094

  20. Dual oxidase regulates neutrophil recruitment in allergic airways.

    PubMed

    Chang, Sandra; Linderholm, Angela; Franzi, Lisa; Kenyon, Nicholas; Grasberger, Helmut; Harper, Richart

    2013-12-01

    Enhanced reactive oxygen species production in allergic airways is well described and correlates with increased airway contractions, inflammatory cell infiltration, goblet cell metaplasia, and mucus hypersecretion. There is also an abundance of interleukin-4/interleukin-13 (IL-4/IL-13)- or interleukin-5-secreting cells that are thought to be central to the pathogenesis of allergic asthma. We postulated that the dual oxidases (DUOX1 and DUOX2), members of the nicotinamide adenine dinucleotide phosphate oxidase family that release hydrogen peroxide (H2O2) in the respiratory tract, are critical proteins in the pathogenesis of allergic airways. DUOX activity is regulated by cytokines, including IL-4 and IL-13, and DUOX-mediated H2O2 influences several important features of allergic asthma: mucin production, IL-8 secretion, and wound healing. The objective of this study was to establish the contribution of DUOXs to the development of allergic asthma in a murine model. To accomplish this goal, we utilized a DUOXA-deficient mouse model (Duoxa(-/-)) that lacked maturation factors for both DUOX1 and DUOX2. Our results are the first to demonstrate evidence of DUOX protein and DUOX functional activity in murine airway epithelium. We also demonstrate that DUOXA maturation factors are required for airway-specific H2O2 production and localization of DUOX to cilia of fully differentiated airway epithelial cells. We compared wild-type and Duoxa(-/-) mice in an ovalbumin exposure model to determine the role of DUOX in allergic asthma. In comparison to DUOX-intact mice, Duoxa(-/-) mice had reduced mucous cell metaplasia and lower levels of TH2 cytokine levels in bronchoalveolar fluid. In addition, increased airway resistance in response to methacholine was observed in Duoxa(+/+) mice, as expected, but was absent in Duoxa(-/-) mice. Surprisingly, Duoxa(-/-) mice had decreased influx of neutrophils in bronchoalveolar fluid and lung tissue sections associated with a lower level of the

  1. Dual Oxidase Regulates Neutrophil Recruitment in Allergic Airways

    PubMed Central

    Chang, Sandra; Linderholm, Angela; Franzi, Lisa; Kenyon, Nicholas; Grasberger, Helmut; Harper, Richart

    2013-01-01

    Enhanced reactive oxygen species production in allergic airways is well described, and correlates with increased airway contractions, inflammatory cell infiltration, goblet cell metaplasia, and mucus hypersecretion. There is also an abundance of interleukin-4/interleukin-13 (IL-4/IL-13) or interleukin-5-secreting cells that are thought to be central to the pathogenesis of allergic asthma. We postulated that dual oxidases (DUOX1 and DUOX2), members of the nicotinamide adenine dinucleotide phosphate oxidase family that release hydrogen peroxide (H2O2) in the respiratory tract, are critical proteins in the pathogenesis of allergic airways. DUOX activity is regulated by cytokines including IL-4 and IL-13, and DUOX-mediated H2O2 influences several important features of allergic asthma: mucin production, IL-8 secretion, and wound healing. The objective of this study was to establish the contribution of DUOX to the development of allergic asthma in a murine model. To accomplish this goal, we utilized a DUOXA-deficient mouse model (Duoxa−/−) that lacked maturation factors for both DUOX1 and DUOX2. Our results are the first to demonstrate evidence of DUOX protein and DUOX functional activity in murine airway epithelium. We also demonstrate that DUOXA maturation factors are required for airway-specific H2O2 production and localization of DUOX to cilia of fully differentiated airway epithelial cells. We compared wild-type and Duoxa−/− mice in an ovalbumin exposure model to determine the role of DUOX in allergic asthma. In comparison to DUOX-intact mice, Duoxa−/− mice had reduced mucous cell metaplasia, and lower levels of TH2 cytokine levels in bronchoalveolar fluid. In addition, increased airway resistance in response to methacholine was observed in Duoxa+/+ mice as expected, but was absent in Duoxa−/− mice. Surprisingly, Duoxa−/− mice had decreased influx of neutrophils in bronchoalveolar fluid and lung tissue sections associated with a lower level of

  2. Clinical assessment and C-reactive protein (CRP), haptoglobin (Hp), and cardiac troponin I (cTnI) values of brachycephalic dogs with upper airway obstruction before and after surgery

    PubMed Central

    Planellas, Marta; Cuenca, Rafaela; Tabar, Maria-Dolores; Bertolani, Coralie; Poncet, Cyrill; Closa, Josep M.; Lorente, Juan; Cerón, José J.; Pastor, Josep

    2015-01-01

    Brachycephalic dogs have unique upper respiratory anatomy with abnormal breathing patterns that are similar to those in humans with obstructive sleep apnea syndrome (OSAS). The objectives of this multicenter prospective study were to assess the effects of surgical correction on clinical signs in dogs with brachycephalic airway obstructive syndrome (BAOS) and to evaluate the levels of several biomarkers [C-reactive protein (CRP); haptoglobin (Hp), and cardiac troponin I (cTnI)] used to determine systemic inflammation and myocardial damage. This study was conducted on 33 dogs with BAOS that were evaluated before and 1 to 2 mo after surgical correction. Palatoplasty was carried out by means of 2 different surgical techniques: carbon dioxide (CO2) laser (n = 12) and electrical scalpel (n = 21). Biomarker levels (CRP, Hp, and cTnI) were determined before and after surgery. There was a significant reduction in respiratory and gastrointestinal signs in dogs with BAOS after surgical treatment (P < 0.001). A greater reduction in respiratory signs (P < 0.002) was obtained using the CO2 laser. No statistical differences were found between CRP and cTnI levels, either before or after surgical correction. Haptoglobin concentration did increase significantly in the postsurgical period (P < 0.008). Surgical treatment in dogs with BAOS reduces clinical signs, regardless of the anatomical components present. Surgical treatment for BAOS is not useful to reduce CRP and Hp levels, probably because BAOS does not induce as obvious an inflammatory process in dogs as in human patients with OSAS. No reduction in cTnI levels was observed 1 mo after surgery in dogs with BAOS, which suggests that some degree of myocardial damage remains. PMID:25673910

  3. Clinical assessment and C-reactive protein (CRP), haptoglobin (Hp), and cardiac troponin I (cTnI) values of brachycephalic dogs with upper airway obstruction before and after surgery.

    PubMed

    Planellas, Marta; Cuenca, Rafaela; Tabar, Maria-Dolores; Bertolani, Coralie; Poncet, Cyrill; Closa, Josep M; Lorente, Juan; Cerón, José J; Pastor, Josep

    2015-01-01

    Brachycephalic dogs have unique upper respiratory anatomy with abnormal breathing patterns that are similar to those in humans with obstructive sleep apnea syndrome (OSAS). The objectives of this multicenter prospective study were to assess the effects of surgical correction on clinical signs in dogs with brachycephalic airway obstructive syndrome (BAOS) and to evaluate the levels of several biomarkers [C-reactive protein (CRP); haptoglobin (Hp), and cardiac troponin I (cTnI)] used to determine systemic inflammation and myocardial damage. This study was conducted on 33 dogs with BAOS that were evaluated before and 1 to 2 mo after surgical correction. Palatoplasty was carried out by means of 2 different surgical techniques: carbon dioxide (CO2) laser (n = 12) and electrical scalpel (n = 21). Biomarker levels (CRP, Hp, and cTnI) were determined before and after surgery. There was a significant reduction in respiratory and gastrointestinal signs in dogs with BAOS after surgical treatment (P < 0.001). A greater reduction in respiratory signs (P < 0.002) was obtained using the CO2 laser. No statistical differences were found between CRP and cTnI levels, either before or after surgical correction. Haptoglobin concentration did increase significantly in the postsurgical period (P < 0.008). Surgical treatment in dogs with BAOS reduces clinical signs, regardless of the anatomical components present. Surgical treatment for BAOS is not useful to reduce CRP and Hp levels, probably because BAOS does not induce as obvious an inflammatory process in dogs as in human patients with OSAS. No reduction in cTnI levels was observed 1 mo after surgery in dogs with BAOS, which suggests that some degree of myocardial damage remains. PMID:25673910

  4. [Airway equipment and its maintenance for a non difficult adult airway management (endotracheal intubation and its alternative: face mask, laryngeal mask airway, laryngeal tube)].

    PubMed

    Francon, D; Estèbe, J P; Ecoffey, C

    2003-08-01

    The airway equipment for a non difficult adult airway management are described: endotracheal tubes with a specific discussion on how to inflate the balloon, laryngoscopes and blades, stylets and intubation guides, oral airways, face masks, laryngeal mask airways and laryngeal tubes. Cleaning and disinfections with the maintenance are also discussed for each type of airway management. PMID:12943860

  5. Angiogenesis is induced by airway smooth muscle strain.

    PubMed

    Hasaneen, Nadia A; Zucker, Stanley; Lin, Richard Z; Vaday, Gayle G; Panettieri, Reynold A; Foda, Hussein D

    2007-10-01

    Angiogenesis is an important feature of airway remodeling in both chronic asthma and chronic obstructive pulmonary disease (COPD). Airways in those conditions are exposed to excessive mechanical strain during periods of acute exacerbations. We recently reported that mechanical strain of human airway smooth muscle (HASM) led to an increase in their proliferation and migration. Sustained growth in airway smooth muscle in vivo requires an increase in the nutritional supply to these muscles, hence angiogenesis. In this study, we examined the hypothesis that cyclic mechanical strain of HASM produces factors promoting angiogenic events in the surrounding vascular endothelial cells. Our results show: 1) a significant increase in human lung microvascular endothelial cell (HMVEC-L) proliferation, migration, and tube formation following incubation in conditioned media (CM) from HASM cells exposed to mechanical strain; 2) mechanical strain of HASM cells induced VEGF expression and release; 3) VEGF neutralizing antibodies inhibited the proliferation, migration, and tube formations of HMVEC-L induced by the strained airway smooth muscle CM; 4) mechanical strain of HASM induced a significant increase in hypoxia-inducible factor-1alpha (HIF-1alpha) mRNA and protein, a transcription factor required for VEGF gene transcription; and 5) mechanical strain of HASM induced HIF-1alpha/VEGF through dual phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) and ERK pathways. In conclusion, exposing HASM cells to mechanical strain induces signal transduction pathway through PI3K/Akt/mTOR and ERK pathways that lead to an increase in HIF-1alpha, a transcription factor required for VEGF expression. VEGF release by mechanical strain of HASM may contribute to the angiogenesis seen with repeated exacerbation of asthma and COPD. PMID:17693481

  6. ASSESSMENT OF NOX EMISSION FACTORS FOR DIRECT-FIRED HEATERS

    EPA Science Inventory

    The report gives results of a review of available data on emission factors for major categories of direct-fired heaters. Systematic studies were analyzed to develop emission factors for oxides of nitrogen (NOx) at various levels of combustion air preheat used in major energy-cons...

  7. Factor Models for Assessing the Relationship between Creativity and Intelligence.

    ERIC Educational Resources Information Center

    Hattie, John; Rogers, H. Jane

    1986-01-01

    This article demonstrates that the usual first-order factor model is inappropriate for analyzing the factor structure of creativity and intelligence tests. An alternative model that allows for the estimation of unique covariance between the fluency and originality scores is proposed. (Author/JAZ)

  8. Ultrasound: A promising tool for contemporary airway management.

    PubMed

    Garg, Rakesh; Gupta, Anju

    2015-11-16

    Airway evaluation and its management remains an ever emerging clinical science. Present airway management tools are static and do not provide dynamic airway management option. Visualized procedures like ultrasound (US) provide point of care real time dynamic views of the airway in perioperative, emergency and critical care settings. US can provide dynamic anatomical assessment which is not possible by clinical examination alone. US aids in detecting gastric contents and the nature of gastric contents (clear fluid, thick turbid or solid) as well. US can help in predicting endotracheal tube size by measuring subglottic diameter and diameter of left main stem bronchus. US was found to be a sensitive in detecting rotational malposition of LMA in children. Also, US is the fastest and highly sensitive tool to rule out a suspected intraoperative pneumothorax. In intensive care units, US helps torule out causes of inadequate ventilation, determine the tracheal width and distance from the skin to predict tracheotomy tube size and shape and assist with percutaneous dilatational tracheostomy. US can help in confirming the correct tracheal tube placement by dynamic visualisation of the endotracheal tube insertion, widening of vocal cords (children), and bilateral lung-sliding and diaphragmatic movement. Thus, ultrasonography has brought a paradigm shift in the practise of airway management. With increasing awareness, portability, accessibility and further sophistication in technology, it is likely to find a place in routine airway management. We are not far from the time when all of us will be carrying a pocket US machine like stethoscopes to corroborate our clinical findings at point of care. PMID:26601094

  9. Ultrasound: A promising tool for contemporary airway management

    PubMed Central

    Garg, Rakesh; Gupta, Anju

    2015-01-01

    Airway evaluation and its management remains an ever emerging clinical science. Present airway management tools are static and do not provide dynamic airway management option. Visualized procedures like ultrasound (US) provide point of care real time dynamic views of the airway in perioperative, emergency and critical care settings. US can provide dynamic anatomical assessment which is not possible by clinical examination alone. US aids in detecting gastric contents and the nature of gastric contents (clear fluid, thick turbid or solid) as well. US can help in predicting endotracheal tube size by measuring subglottic diameter and diameter of left main stem bronchus. US was found to be a sensitive in detecting rotational malposition of LMA in children. Also, US is the fastest and highly sensitive tool to rule out a suspected intraoperative pneumothorax. In intensive care units, US helps torule out causes of inadequate ventilation, determine the tracheal width and distance from the skin to predict tracheotomy tube size and shape and assist with percutaneous dilatational tracheostomy. US can help in confirming the correct tracheal tube placement by dynamic visualisation of the endotracheal tube insertion, widening of vocal cords (children), and bilateral lung-sliding and diaphragmatic movement. Thus, ultrasonography has brought a paradigm shift in the practise of airway management. With increasing awareness, portability, accessibility and further sophistication in technology, it is likely to find a place in routine airway management. We are not far from the time when all of us will be carrying a pocket US machine like stethoscopes to corroborate our clinical findings at point of care. PMID:26601094

  10. Jaw thrust can deteriorate upper airway patency.

    PubMed

    von Ungern-Sternberg, B S; Erb, T O; Frei, F J

    2005-04-01

    Upper airway obstruction is a frequent problem in spontaneously breathing children undergoing anesthesia or sedation procedures. Failure to maintain a patent airway can rapidly result in severe hypoxemia, bradycardia, or asystole, as the oxygen demand of children is high and oxygen reserve is low. We present two children with cervical masses in whom upper airway obstruction exaggerated while the jaw thrust maneuver was applied during induction of anesthesia. This deterioration in airway patency was probably caused by medial displacement of the lateral tumorous tissues which narrowed the pharyngeal airway. PMID:15777312

  11. Mucoactive agents for airway mucus hypersecretory diseases.

    PubMed

    Rogers, Duncan F

    2007-09-01

    Airway mucus hypersecretion is a feature of a number of severe respiratory diseases, including asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF). However, each disease has a different airway inflammatory response, with consequent, and presumably linked, mucus hypersecretory phenotype. Thus, it is possible that optimal treatment of the mucus hypersecretory element of each disease should be disease-specific. Nevertheless, mucoactive drugs are a longstanding and popular therapeutic option, and numerous compounds (eg, N-acetylcysteine, erdosteine, and ambroxol) are available for clinical use worldwide. However, rational recommendation of these drugs in guidelines for management of asthma, COPD, or CF has been hampered by lack of information from well-designed clinical trials. In addition, the mechanism of action of most of these drugs is unknown. Consequently, although it is possible to categorize them according to putative mechanisms of action, as expectorants (aid and/or induce cough), mucolytics (thin mucus), mucokinetics (facilitate cough transportability), and mucoregulators (suppress mechanisms underlying chronic mucus hypersecretion, such as glucocorticosteroids), it is likely that any beneficial effects are due to activities other than, or in addition to, effects on mucus. It is also noteworthy that the mucus factors that favor mucociliary transport (eg, thin mucus gel layer, "ideal" sol depth, and elasticity greater than viscosity) are opposite to those that favor cough effectiveness (thick mucus layer, excessive sol height, and viscosity greater than elasticity), which indicates that different mucoactive drugs would be required for treatment of mucus obstruction in proximal versus distal airways, or in patients with an impaired cough reflex. With the exception of mucoregulatory agents, whose primary action is unlikely to be directed against mucus, well-designed clinical trials are required to unequivocally determine the

  12. Delivery of Alpha-1 Antitrypsin to Airways.

    PubMed

    Griese, Matthias; Scheuch, Gerhard

    2016-08-01

    Treatment with exogenous alpha-1 antitrypsin (AAT), a potent serine protease inhibitor, was developed originally for chronic obstructive pulmonary disease associated with AAT deficiency; however, other lung conditions involving neutrophilic inflammation and proteolytic tissue injury related to neutrophil elastase and other serine proteases may also be considered for AAT therapy. These conditions include bronchiectasis caused by primary ciliary dyskinesia, cystic fibrosis, and other diseases associated with an increased free elastase activity in the airways. Inhaled AAT may be a viable option to counteract proteolytic tissue damage. This form of treatment requires efficient drug delivery to the targeted pulmonary compartment. Aerosol technology meeting this requirement is currently available and offers an alternative therapeutic approach to systemic AAT administration. To date, early studies in humans have shown biochemical efficacy and have established the safety of inhaled AAT. However, to bring aerosol AAT therapy to patients, large phase 3 protocols in carefully selected patient populations (i.e., subgroups of patients with AAT deficiency, cystic fibrosis, or other lung diseases with bronchiectasis) will be needed with clinical end points in addition to the measurement of proteolytic activity in the airway. The outcomes likely will have to include lung function, lung structure assessed by computed tomography imaging, disease exacerbations, health status, and mortality. PMID:27564672

  13. Fourteen cases of imposed upper airway obstruction.

    PubMed Central

    Samuels, M P; McClaughlin, W; Jacobson, R R; Poets, C F; Southall, D P

    1992-01-01

    Imposed upper airway obstruction was diagnosed as the cause of recurrent and severe cyanotic episodes in 14 patients. Episodes started between 0.8 and 33 months of age (median 1.4) and occurred over a period of 0.8 to 20 months (median 3.5). Diagnosis was made by covert video surveillance, instituted after either (a) the observation that episodes began only in the presence of one person, or (b) characteristic findings on physiological recordings, lasting between 12 hours and three weeks, performed in hospital or at home. Surveillance was undertaken for between 15 minutes and 12 days (median 24 hours) and resulted in safety for the patient and psychiatric assessment of the parent: mother (n = 12), father (n = 1), and grandmother (n = 1). These revealed histories of sexual, physical, or emotional abuse (n = 11), self harm (n = 9), factitious illness (n = 7), eating disorder (n = 10), and previous involvement with a psychiatrist (n = 7). Management of the abusing parents is complex, but recognition of their psychosocial characteristics may allow earlier diagnosis. Imposed upper airway obstruction should be considered and excluded by physiological recordings in any infant or young child with recurrent cyanotic episodes. If physiological recordings fail to substantiate a natural cause for episodes, covert video surveillance may be essential to protect the child from further injury or death. PMID:1543373

  14. Effect of an anti-Mo1 MAb on ozone-induced airway inflammation and airway hyperresponsiveness in dogs

    SciTech Connect

    Li, Z.; Daniel, E.E.; Lane, C.G.; Arnaout, M.A.; O'Byrne, P.M. )

    1992-12-01

    Ozone inhalation causes neutrophil migration into the airway and airway hyperresponsiveness in dogs. The leukocyte adhesion molecule Mo1 (CD11b/CD18) is a heterodimeric glycoprotein the expression of which is necessary for neutrophil adhesion to endothelium. To evaluate the contribution of Mo1 to ozone-induced neutrophil influx and airway hyperresponsiveness, six dogs were treated intravenously with an Anti-Mo1 monoclonal antibody (3.75 mg/kg in normal saline) that binds to both human and canine Mo1, or the diluent alone, 1.5 h before inhaling ozone (3 ppm for 30 min), or dry air. Airway responses to doubling doses of inhaled acetylcholine (ACh) were measured before and after inhalation of ozone. Neutrophil influx was assessed by bronchoalveolar lavage (BAL) performed after the second ACh inhalation. Treatment with anti-Mo1 prevented the ozone-induced influx of neutrophils into BAL. After diluent and inhaled dry air, the neutrophil count in BAL was 1.49 +/- 1.26 (SE) x 10(4) (5.0% of total cells). After diluent and inhaled ozone, the neutrophil count increased to 7.27 +/- 3.22 (SE) x 10(4) (22.6% of total cells) (P < 0.05). After anti-Mo1 and inhaled ozone, the neutrophil count was 1.48 +/- 0.62 (SE) x 10(4) (8.5% of total cells). Treatment with anti-Mo1 also significantly reduced the number of eosinophils in BAL after ozone. Ozone-induced ACh airway hyperresponsiveness was not prevented by treatment with anti-Mo1. These results indicate that expression of Mo1 is necessary for ozone-induced neutrophil migration into the airway lumen.

  15. Surface modeling and segmentation of the 3D airway wall in MSCT

    NASA Astrophysics Data System (ADS)

    Ortner, Margarete; Fetita, Catalin; Brillet, Pierre-Yves; Pr"teux, Françoise; Grenier, Philippe

    2011-03-01

    Airway wall remodeling in asthma and chronic obstructive pulmonary disease (COPD) is a well-known indicator of the pathology. In this context, current clinical studies aim for establishing the relationship between the airway morphological structure and its function. Multislice computed tomography (MSCT) allows morphometric assessment of airways, but requires dedicated segmentation tools for clinical exploitation. While most of the existing tools are limited to cross-section measurements, this paper develops a fully 3D approach for airway wall segmentation. Such approach relies on a deformable model which is built up as a patient-specific surface model at the level of the airway lumen and deformed to reach the outer surface of the airway wall. The deformation dynamics obey a force equilibrium in a Lagrangian framework constrained by a vector field which avoids model self-intersections. The segmentation result allows a dense quantitative investigation of the airway wall thickness with a deeper insight at bronchus subdivisions than classic cross-section methods. The developed approach has been assessed both by visual inspection of 2D cross-sections, performed by two experienced radiologists on clinical data obtained with various protocols, and by using a simulated ground truth (pulmonary CT image model). The results confirmed a robust segmentation in intra-pulmonary regions with an error in the range of the MSCT image resolution and underlined the interest of the volumetric approach versus purely 2D methods.

  16. Laryngo-tracheal ultrasonography to confirm correct endotracheal tube and laryngeal mask airway placement.

    PubMed

    Wojtczak, Jacek A; Cattano, Davide

    2014-12-01

    Waveform capnography was recommended as the most reliable method to confirm correct endotracheal tube or laryngeal mask airway placements. However, capnography may be unreliable during cardiopulmonary resuscitation and during low flow states. It may lead to an unnecessary removal of a well-placed endotracheal tube, re-intubation and interruption of chest compressions. Real-time upper airway (laryngo-tracheal) ultrasonography to confirm correct endotracheal tube placement was shown to be very useful in cadaveric models and during emergency intubation. Tracheal ultrasonography does not interrupt chest compressions and is not affected by low pulmonary flow or airway obstruction, but is limited by ultrasonography scattering and acoustic artifacts generated in air - mucosa interfaces. Sonographic upper airway assessment emerges as a rapid and easily available method to predict difficult intubation, to assess the laryngeal and hypopharyngeal size and visualize the position of the laryngeal mask airway in situ. This study demonstrates that the replacement of air with saline in endotracheal tube or laryngeal mask airway cuffs and the use of the contrast agents enables detection of cuffs in the airway. It also allows visualization of the surrounding structures or tissues as the ultrasound beam can be transmitted through the fluid - filled cuffs without being reflected from air - mucosal interfaces. PMID:26672974

  17. Systems-level airway models of bronchoconstriction.

    PubMed

    Donovan, Graham M

    2016-09-01

    Understanding lung and airway behavior presents a number of challenges, both experimental and theoretical, but the potential rewards are great in terms of both potential treatments for disease and interesting biophysical phenomena. This presents an opportunity for modeling to contribute to greater understanding, and here, we focus on modeling efforts that work toward understanding the behavior of airways in vivo, with an emphasis on asthma. We look particularly at those models that address not just isolated airways but many of the important ways in which airways are coupled both with each other and with other structures. This includes both interesting phenomena involving the airways and the layer of airway smooth muscle that surrounds them, and also the emergence of spatial ventilation patterns via dynamic airway interaction. WIREs Syst Biol Med 2016, 8:459-467. doi: 10.1002/wsbm.1349 For further resources related to this article, please visit the WIREs website. PMID:27348217

  18. The Importance of Airway Management in Trauma

    PubMed Central

    Jacobs, Lenworth M.

    1988-01-01

    The airway is the most important priority in the management of the severely injured patient. It is essential to open and clear the airway to allow free access of air to the distal endobronchial tree. Manual methods of opening the airway are described. Numerous methods for establishing definitive control of the airway as well as the associated devices currently available to maintain control are described. Once the airway is maintained, it is important to ensure adequate oxygenation and ventilation through the airway. Modern portable devices that monitor the carbon dioxide in the expired air at the end of each breath are currently available. These devices allow the physician to verify the position of the tube in the airway as well as to continuously monitor the efficacy of ventilation. PMID:3073226

  19. Sarcoidosis of the upper and lower airways.

    PubMed

    Morgenthau, Adam S; Teirstein, Alvin S

    2011-12-01

    Sarcoidosis is a systemic granulomatous disease of undetermined etiology characterized by a variable clinical presentation and disease course. Although clinical granulomatous inflammation may occur within any organ system, more than 90% of sarcoidosis patients have lung disease. Sarcoidosis is considered an interstitial lung disease that is frequently characterized by restrictive physiologic dysfunction on pulmonary function tests. However, sarcoidosis also involves the airways (large and small), causing obstructive airways disease. It is one of a few interstitial lung diseases that affects the entire length of the respiratory tract - from the nose to the terminal bronchioles - and causes a broad spectrum of airways dysfunction. This article examines airway dysfunction in sarcoidosis. The anatomical structure of the airways is the organizational framework for our discussion. We discuss sarcoidosis involving the nose, sinuses, nasal passages, larynx, trachea, bronchi and small airways. Common complications of airways disease, such as, atelectasis, fibrosis, bullous leions, bronchiectasis, cavitary lesions and mycetomas, are also reviewed. PMID:22082167

  20. Proteomic analysis of the asthmatic airway.

    PubMed

    Wiktorowicz, John E; Jamaluddin, Mohammad

    2014-01-01

    Proteomic investigations in general utilize varied technologies for sample preparation, separations, quantification, protein identification, and biological rationalization. Their applications range from pure discovery and mechanistic studies to biomarker discovery/verification/validation. In each specific case, the analytical strategy to be implemented is tailored to the type of sample that serves as the target of the investigations. Proteomic investigations take into consideration sample complexity, the cellular heterogeneity (particularly from tissues), the potential dynamic range of the protein and peptide abundance within the sample, the likelihood of posttranslational modifications (PTM), and other important factors that might influence the final output of the study. We describe the sample types typically used for proteomic investigations into the biology of asthma and review the most recent related publications with special attention to those that deal with the unique airway samples such as bronchoalveolar lavage fluids (BALF), epithelial lining fluid and cells (ELF), induced sputum (IS), and exhaled breath condensate (EBC). Finally, we describe the newest proteomics approaches to sample preparation of the unique airway samples, BALF and IS. PMID:24162912

  1. Multi-Level Model of Contextual Factors and Teachers' Assessment Practices: An Integrative Review of Research

    ERIC Educational Resources Information Center

    Fulmer, Gavin W.; Lee, Iris C. H.; Tan, Kelvin H. K.

    2015-01-01

    We present a multi-level model of contextual factors that may influence teachers' assessment practices, and use this model in a selected review of existing literature on teachers' assessment knowledge, views and conceptions with respect to these contextual factors. Adapting Kozma's model, we distinguish three levels of influence on teachers'…

  2. Post-Exposure Antioxidant Treatment in Rats Decreases Airway Hyperplasia and Hyperreactivity Due to Chlorine Inhalation

    PubMed Central

    Bracher, Andreas; Doran, Stephen F.; Squadrito, Giuseppe L.; Fernandez, Solana; Postlethwait, Edward M.; Bowen, Larry; Matalon, Sadis

    2012-01-01

    We assessed the safety and efficacy of combined intravenous and aerosolized antioxidant administration to attenuate chlorine gas–induced airway alterations when administered after exposure. Adult male Sprague-Dawley rats were exposed to air or 400 parts per million (ppm) chlorine (a concentration likely to be encountered in the vicinity of industrial accidents) in environmental chambers for 30 minutes, and returned to room air, and they then received a single intravenous injection of ascorbic acid and deferoxamine or saline. At 1 hour and 15 hours after chlorine exposure, the rats were treated with aerosolized ascorbate and deferoxamine or vehicle. Lung antioxidant profiles, plasma ascorbate concentrations, airway morphology, and airway reactivity were evaluated at 24 hours and 7 days after chlorine exposure. At 24 hours after exposure, chlorine-exposed rats had significantly lower pulmonary ascorbate and reduced glutathione concentrations. Treatment with antioxidants restored depleted ascorbate in lungs and plasma. At 7 days after exposure, in chlorine-exposed, vehicle-treated rats, the thickness of the proximal airways was 60% greater than in control rats, with twice the amount of mucosubstances. Airway resistance in response to methacholine challenge was also significantly elevated. Combined treatment with intravenous and aerosolized antioxidants restored airway morphology, the amount of airway mucosubstances, and airway reactivity to control levels by 7 days after chlorine exposure. Our results demonstrate for the first time, to the best of our knowledge, that severe injury to major airways in rats exposed to chlorine, as characterized by epithelial hyperplasia, mucus accumulation, and airway hyperreactivity, can be reversed in a safe and efficacious manner by the post-exposure administration of ascorbate and deferoxamine. PMID:22162906

  3. Effect of endothelin antagonism on the production of cytokines in eosinophilic airway inflammation.

    PubMed

    Finsnes, F; Lyberg, T; Christensen, G; Skjønsberg, O H

    2001-04-01

    Endothelin (ET)-1 has been launched as an important mediator in bronchial asthma, which is an eosinophilic airway inflammation. However, the interplay between ET-1 and other proinflammatory mediators during the development of airway inflammation has not been elucidated. We wanted to study 1) whether the production of ET-1 precedes the production of other proinflammatory mediators and 2) whether ET-1 stimulates the production of these mediators within the airways. These hypotheses were studied during the development of an eosinophilic airway inflammation in rats. The increase in ET-1 mRNA level in lung tissue preceded the increase in mRNA levels of tumor necrosis factor-alpha, interleukin (IL)-1beta, and IL-8. Treatment of the animals with the ET receptor antagonist bosentan resulted in a substantial decrease in the concentrations of tumor necrosis factor-alpha, IL-4, IL-1beta, interferon-gamma, and ET-1 in bronchoalveolar lavage fluid. In conclusion, the synthesis of ET-1 as measured by increased mRNA level precedes the synthesis of other proinflammatory cytokines of importance for the development of an eosinophilic airway inflammation, and ET antagonism inhibits the production of these mediators within the airways. Whether treatment with ET antagonists will prove beneficial for patients with eosinophilic airway inflammations like bronchial asthma is not yet known. PMID:11238005

  4. Mouse models of osteoarthritis: modelling risk factors and assessing outcomes.

    PubMed

    Fang, Hang; Beier, Frank

    2014-07-01

    Osteoarthritis (OA) is a prevalent musculoskeletal disease that results in pain and low quality of life for patients, as well as enormous medical and socioeconomic burdens. The molecular mechanisms responsible for the initiation and progression of OA are still poorly understood. As such, mouse models of the disease are having increasingly important roles in OA research owing to the advancements of microsurgical techniques and the use of genetically modified mice, as well as the development of novel assessment tools. In this Review, we discuss available mouse models of OA and applicable assessment tools in studies of experimental OA. PMID:24662645

  5. The effect of phytocannabinoids on airway hyper-responsiveness, airway inflammation, and cough.

    PubMed

    Makwana, Raj; Venkatasamy, Radhakrishnan; Spina, Domenico; Page, Clive

    2015-04-01

    Cannabis has been demonstrated to have bronchodilator, anti-inflammatory, and antitussive activity in the airways, but information on the active cannabinoids, their receptors, and the mechanisms for these effects is limited. We compared the effects of Δ(9)-tetrahydrocannabinol, cannabidiol, cannabigerol, cannabichromene, cannabidiolic acid, and tetrahydrocannabivarin on contractions of the guinea pig-isolated trachea and bronchoconstriction induced by nerve stimulation or methacholine in anesthetized guinea pigs following exposure to saline or the proinflammatory cytokine, tumor necrosis factor α (TNF-α). CP55940 (2-[(1R,2R,5R)-5-hydroxy-2-(3-hydroxypropyl) cyclohexyl]-5-(2-methyloctan-2-yl)phenol), a synthetic cannabinoid agonist, was also investigated in vitro. The cannabinoids were also evaluated on TNF-α- and lipopolysaccharide-induced leukocyte infiltration into the lungs and citric acid-induced cough responses in guinea pigs. TNF-α, but not saline, augmented tracheal contractility and bronchoconstriction induced by nerve stimulation, but not methacholine. Δ(9)-Tetrahydrocannabinol and CP55940 reduced TNF-α-enhanced nerve-evoked contractions in vitro to the magnitude of saline-incubated trachea. This effect was antagonized by the cannabinoid 1 (CB(1)) and CB(2) receptor antagonists AM251 [N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-caroxamide] and JTE907 [N-(1,3-benzodioxol-5-ylmethyl)-1,2-dihydro-7-methoxy-2-oxo-8-(pentyloxy)-3-quinolinecarboxamide], respectively. Tetrahydrocannabivarin partially inhibited the TNF-α-enhanced nerve-evoked contractions, whereas the other cannabinoids were without effect. The effect of cannabidiol and Δ(9)-tetrahydrocannabinol together did not differ from that of the latter alone. Only Δ(9)-tetrahydrocannabinol inhibited TNF-α-enhanced vagal-induced bronchoconstriction, neutrophil recruitment to the airways, and citric acid-induced cough responses. TNF-α potentiated contractions

  6. Effect of Host Modification and Age on Airway Epithelial Gene Transfer Mediated by a Murine Leukemia Virus-Derived Vector

    PubMed Central

    Johnson, Larry G.; Mewshaw, Jennifer P.; Ni, Hong; Friedmann, Theodore; Boucher, Richard C.; Olsen, John C.

    1998-01-01

    To study retroviral gene transfer to airway epithelia, we used a transient transfection technique to generate high titers (∼109 infectious units/ml after concentration) of murine leukemia virus (MuLV)-derived vectors pseudotyped with the vesicular stomatitis virus envelope glycoprotein (VSV-G). Transformed (CFT1) and primary airway epithelial cells were efficiently transduced by a VSV-G-pseudotyped lacZ vector (HIT-LZ) in vitro. CFT1 cells and primary cystic fibrosis (CF) airway cell monolayers infected with a vector (HIT-LCFSN) containing human CF transmembrane conductance regulator (CFTR) in the absence of selection expressed CFTR, as assessed by Western blot analysis, and exhibited functional correction of CFTR-mediated Cl− secretion. In vitro studies of persistence suggested that pseudotransduction was not a significant problem with our vector preparations. In a sulfur dioxide (SO2) inhalational injury model, bromodeoxyuridine (BrdU) incorporation rates were measured and found to exceed 50% in SO2-injured murine tracheal epithelium. HIT-LZ vector (multiplicity of infection of ∼10) instilled into the SO2-injured tracheas of anesthetized mice transduced 6.1% ± 1.3% of superficial airway cells in tracheas of weanling mice (3 to 4 weeks old; n = 10), compared to 1.4 ± 0.9% in mice 5 weeks of age (n = 4) and 0.2% in mice older than 6 weeks (n = 15). No evidence for gene transfer following delivery of HIT-LZ to tracheas of either weanling or older mice not injured with SO2 was detected. Because only a small fraction of BrdU-labeled airway cells were transduced, we examined the stability of the vector. No significant loss of vector infectivity over intervals (2 h) paralleling those of in vivo protocols was detected in in vitro assays using CFT1 cells. In summary, high-titer vectors permitted complementation of defective CFTR-mediated Cl− transport in CF airway cells in vitro without selection and demonstrated that the age of the animal appeared to be a major

  7. Factor Structure and Construct Validity of the Scale for the Assessment of Negative Symptoms.

    ERIC Educational Resources Information Center

    Sayers, Steven L.; And Others

    1996-01-01

    Confirmatory factor analysis (CFA) was used to examine the underlying structure of negative symptoms of schizophrenia as measured by the Scale for the Assessment of Negative Symptoms (SANS). CFA results from the assessment of 401 patients were largely supported by CFA results from a second assessment of 345 patients. (SLD)

  8. Noninvasive clearance of airway secretions.

    PubMed

    Hardy, K A; Anderson, B D

    1996-06-01

    Airway clearance techniques are indicated for specific diseases that have known clearance abnormalities (Table 2). Murray and others have commented that such techniques are required only for patients with a daily sputum production of greater than 30 mL. The authors have observed that patients with diseases known to cause clearance abnormalities can have sputum clearance with some techniques, such as positive expiratory pressure, autogenic drainage, and active cycle of breathing techniques, when PDPV has not been effective. Hasani et al has shown that use of the forced exhalatory technique in patients with nonproductive cough still resulted in movement of secretions proximally from all regions of the lung in patients with airway obstruction. It is therefore reasonable to consider airway clearance techniques for any patient who has a disease known to alter mucous clearance, including CF, dyskinetic cilia syndromes, and bronchiectasis from any cause. Patients with atelectasis from mucous plugs and hypersecretory states, such as asthma and chronic bronchitis, patients with pain secondary to surgical procedures, and patients with neuromuscular disease, weak cough, and abnormal patency of the airway may also benefit from the application of airway clearance techniques. Infants and children up to 3 years of age with airway clearance problems need to be treated with PDPV. Manual percussion with hands alone or a flexible face mask or cup and small mechanical vibrator/percussors, such as the ultrasonic devices, can be used. The intrapulmonary percussive ventilator shows growing promise in this area. The high-frequency oscillator is not supplied with vests of appropriate sizes for tiny babies and has not been studied in this group. Young patients with neuromuscular disease may require assisted ventilation and airway oscillations can be applied. CPAP alone has been shown to improve achievable flow rates that will increase air-liquid interactions for patients with these diseases

  9. Factors Affecting Validity of a Regionally Administered Assessment Center.

    ERIC Educational Resources Information Center

    Schmitt, Neal; And Others

    1990-01-01

    Evaluated degree to which single assessment center implemented in multiple sites yielded generalizable validities in school administrators (N=520). Found correction for range restriction, criterion unreliability, and sampling error did not account for large portion of variability in validity coefficients. Found type of assessor used, the center's…

  10. Teacher-Reported Goal Structures: Assessing Factor Structure and Invariance

    ERIC Educational Resources Information Center

    Wolters, Christopher A.; Fan, Weihua; Daugherty, Stacy

    2011-01-01

    The purpose of this study was to extend the research on achievement goal theory by examining the measurement and understanding of goal structures using teacher-reported data. A large number of elementary, middle, and high school teachers completed an online survey that included items assessing their use of instructional practices associated with…

  11. A Factor Structure of Wellness: Theory, Assessment, Analysis, and Practice

    ERIC Educational Resources Information Center

    Hattie, John A.; Myers, Jane E.; Sweeney, Thomas J.

    2004-01-01

    The Wheel of Wellness, a theoretical model of well-being, incorporates 16 dimensions of healthy functioning that can be assessed using the Wellness Evaluation of Lifestyle (WEL; J. E. Myers, T. J. Sweeney, & J. M. Witmer, 1998). A series of studies are reported concerning the development and validation of the WEL based on a large database. In the…

  12. Factors Affecting the Adoption of an E-Assessment System

    ERIC Educational Resources Information Center

    McCann, Ann L.

    2010-01-01

    A case study was conducted in 2006-07 to explore how one US campus implemented a centralised e-assessment system. The study specifically measured the extent of adoption by faculty members, identified their reasons for adoption and evaluated the impact on teaching and learning. The purposes of the system, entitled researching learning (REAL, a…

  13. State Writing Assessment: Inclusion of Motivational Factors in Writing Tasks

    ERIC Educational Resources Information Center

    Olinghouse, Natalie G.; Zheng, Jinjie; Morlock, Larissa

    2012-01-01

    This study evaluated large-scale state writing assessments for the inclusion of motivational characteristics in the writing task and written prompt. We identified 6 motivational variables from the authentic activity literature: time allocation, audience specification, audience intimacy, definition of task, allowance for multiple perspectives, and…

  14. A Quantitative Assessment of Factors Affecting College Sports' Team Unity

    ERIC Educational Resources Information Center

    Aghazadeh, Seyed-Mahmoud; Kyei, Kwasi

    2009-01-01

    The competitiveness of National Collegiate Association (NCAA) schools increases in intensity each year. With the increased pressure on college sport staffs to be undefeated season after season, coaches have to find ways to keep players happy; to do this, they have to find factors that contribute to unify the players. It is nearly impossible to…

  15. Planning for Change: Assessing Internal and External Environmental Factors.

    ERIC Educational Resources Information Center

    Coffey, Janis Cox

    This report provides, first, an overview of the external and internal environmental factors affecting planning in California's community colleges; and, second, an examination of the influence of the demographics of the Los Rios Community College District (LRCCD). After an executive summary, introductory material discusses ways in which change can…

  16. Improvement of Photon Buildup Factors for Radiological Assessment

    SciTech Connect

    F.G. Schirmers

    2006-07-01

    Slant-path buildup factors for photons between 1 keV and 10 MeV for nine radiation shielding materials (air, aluminum, concrete, iron, lead, leaded glass, polyethylene, stainless steel, and water) are calculated with the most recent cross-section data available using Monte Carlo and discrete ordinates methods. Discrete ordinates calculations use a 244-group energy structure that is based on previous research at Los Alamos National Laboratory (LANL), but extended with the results of this thesis, and its focused studies on low-energy photon transport and the effects of group widths in multigroup calculations. Buildup factor calculations in discrete ordinates benefit from coupled photon/electron cross sections to account for secondary photon effects. Also, ambient dose equivalent (herein referred to as dose) buildup factors were analyzed at lower energies where corresponding response functions do not exist in literature. The results of these studies are directly applicable to radiation safety at LANL, where the dose modeling tool Pandemonium is used to estimate worker dose in plutonium handling facilities. Buildup factors determined in this thesis will be used to enhance the code's modeling capabilities, but should be of interest to the radiation shielding community.

  17. Assessing Factors Influencing Student Academic Success in Law School

    ERIC Educational Resources Information Center

    Detwiler, Robert R.

    2011-01-01

    The literature on student academic success of law students is limited to mostly single institution studies, and as such, a nationwide, multi-institutional empirical study of the factors that predict student academic success is greatly needed by higher education scholars, law school admission officers, faculty, and administrators. This dissertation…

  18. Nrf2 protects against airway disorders

    SciTech Connect

    Cho, Hye-Youn; Kleeberger, Steven R.

    2010-04-01

    Nuclear factor-erythroid 2 related factor 2 (Nrf2) is a ubiquitous master transcription factor that regulates antioxidant response elements (AREs)-mediated expression of antioxidant enzyme and cytoprotective proteins. In the unstressed condition, Kelch-like ECH-associated protein 1 (Keap1) suppresses cellular Nrf2 in cytoplasm and drives its proteasomal degradation. Nrf2 can be activated by diverse stimuli including oxidants, pro-oxidants, antioxidants, and chemopreventive agents. Nrf2 induces cellular rescue pathways against oxidative injury, abnormal inflammatory and immune responses, apoptosis, and carcinogenesis. Application of Nrf2 germ-line mutant mice has identified an extensive range of protective roles for Nrf2 in experimental models of human disorders in the liver, gastrointestinal tract, airway, kidney, brain, circulation, and immune or nerve system. In the lung, lack of Nrf2 exacerbated toxicity caused by multiple oxidative insults including supplemental respiratory therapy (e.g., hyperoxia, mechanical ventilation), cigarette smoke, allergen, virus, bacterial endotoxin and other inflammatory agents (e.g., carrageenin), environmental pollution (e.g., particles), and a fibrotic agent bleomycin. Microarray analyses and bioinformatic studies elucidated functional AREs and Nrf2-directed genes that are critical components of signaling mechanisms in pulmonary protection by Nrf2. Association of loss of function with promoter polymorphisms in NRF2 or somatic and epigenetic mutations in KEAP1 and NRF2 has been found in cohorts of patients with acute lung injury/acute respiratory distress syndrome or lung cancer, which further supports the role for NRF2 in these lung diseases. In the current review, we address the role of Nrf2 in airways based on emerging evidence from experimental oxidative disease models and human studies.

  19. Assessing Young Adolescents' Personality with the Five-Factor Personality Inventory

    ERIC Educational Resources Information Center

    Hendriks, A. A. Jolijn; Kuyper, Hans; Offringa, G. Johan; Van der Werf, Margaretha P. C.

    2008-01-01

    The Five-Factor Personality Inventory (FFPI) assesses a person's position on the (Dutch) psycholexically based Big Five factors: Extraversion, Agreeableness, Conscientiousness, Emotional Stability, and Autonomy. FFPI factor scores are reliable and valid if ratings are made by adults. The present study yields preliminary evidence of whether young…

  20. Integrated care pathways for airway diseases (AIRWAYS-ICPs).

    PubMed

    Bousquet, J; Addis, A; Adcock, I; Agache, I; Agusti, A; Alonso, A; Annesi-Maesano, I; Anto, J M; Bachert, C; Baena-Cagnani, C E; Bai, C; Baigenzhin, A; Barbara, C; Barnes, P J; Bateman, E D; Beck, L; Bedbrook, A; Bel, E H; Benezet, O; Bennoor, K S; Benson, M; Bernabeu-Wittel, M; Bewick, M; Bindslev-Jensen, C; Blain, H; Blasi, F; Bonini, M; Bonini, S; Boulet, L P; Bourdin, A; Bourret, R; Bousquet, P J; Brightling, C E; Briggs, A; Brozek, J; Buhl, R; Bush, A; Caimmi, D; Calderon, M; Calverley, P; Camargos, P A; Camuzat, T; Canonica, G W; Carlsen, K H; Casale, T B; Cazzola, M; Cepeda Sarabia, A M; Cesario, A; Chen, Y Z; Chkhartishvili, E; Chavannes, N H; Chiron, R; Chuchalin, A; Chung, K F; Cox, L; Crooks, G; Crooks, M G; Cruz, A A; Custovic, A; Dahl, R; Dahlen, S E; De Blay, F; Dedeu, T; Deleanu, D; Demoly, P; Devillier, P; Didier, A; Dinh-Xuan, A T; Djukanovic, R; Dokic, D; Douagui, H; Dubakiene, R; Eglin, S; Elliot, F; Emuzyte, R; Fabbri, L; Fink Wagner, A; Fletcher, M; Fokkens, W J; Fonseca, J; Franco, A; Frith, P; Furber, A; Gaga, M; Garcés, J; Garcia-Aymerich, J; Gamkrelidze, A; Gonzales-Diaz, S; Gouzi, F; Guzmán, M A; Haahtela, T; Harrison, D; Hayot, M; Heaney, L G; Heinrich, J; Hellings, P W; Hooper, J; Humbert, M; Hyland, M; Iaccarino, G; Jakovenko, D; Jardim, J R; Jeandel, C; Jenkins, C; Johnston, S L; Jonquet, O; Joos, G; Jung, K S; Kalayci, O; Karunanithi, S; Keil, T; Khaltaev, N; Kolek, V; Kowalski, M L; Kull, I; Kuna, P; Kvedariene, V; Le, L T; Lodrup Carlsen, K C; Louis, R; MacNee, W; Mair, A; Majer, I; Manning, P; de Manuel Keenoy, E; Masjedi, M R; Melen, E; Melo-Gomes, E; Menzies-Gow, A; Mercier, G; Mercier, J; Michel, J P; Miculinic, N; Mihaltan, F; Milenkovic, B; Molimard, M; Momas, I; Montilla-Santana, A; Morais-Almeida, M; Morgan, M; N'Diaye, M; Nafti, S; Nekam, K; Neou, A; Nicod, L; O'Hehir, R; Ohta, K; Paggiaro, P; Palkonen, S; Palmer, S; Papadopoulos, N G; Papi, A; Passalacqua, G; Pavord, I; Pigearias, B; Plavec, D; Postma, D S; Price, D; Rabe, K F; Radier Pontal, F; Redon, J; Rennard, S; Roberts, J; Robine, J M; Roca, J; Roche, N; Rodenas, F; Roggeri, A; Rolland, C; Rosado-Pinto, J; Ryan, D; Samolinski, B; Sanchez-Borges, M; Schünemann, H J; Sheikh, A; Shields, M; Siafakas, N; Sibille, Y; Similowski, T; Small, I; Sola-Morales, O; Sooronbaev, T; Stelmach, R; Sterk, P J; Stiris, T; Sud, P; Tellier, V; To, T; Todo-Bom, A; Triggiani, M; Valenta, R; Valero, A L; Valiulis, A; Valovirta, E; Van Ganse, E; Vandenplas, O; Vasankari, T; Vestbo, J; Vezzani, G; Viegi, G; Visier, L; Vogelmeier, C; Vontetsianos, T; Wagstaff, R; Wahn, U; Wallaert, B; Whalley, B; Wickman, M; Williams, D M; Wilson, N; Yawn, B P; Yiallouros, P K; Yorgancioglu, A; Yusuf, O M; Zar, H J; Zhong, N; Zidarn, M; Zuberbier, T

    2014-08-01

    The objective of Integrated Care Pathways for Airway Diseases (AIRWAYS-ICPs) is to launch a collaboration to develop multi-sectoral care pathways for chronic respiratory diseases in European countries and regions. AIRWAYS-ICPs has strategic relevance to the European Union Health Strategy and will add value to existing public health knowledge by: 1) proposing a common framework of care pathways for chronic respiratory diseases, which will facilitate comparability and trans-national initiatives; 2) informing cost-effective policy development, strengthening in particular those on smoking and environmental exposure; 3) aiding risk stratification in chronic disease patients, using a common strategy; 4) having a significant impact on the health of citizens in the short term (reduction of morbidity, improvement of education in children and of work in adults) and in the long-term (healthy ageing); 5) proposing a common simulation tool to assist physicians; and 6) ultimately reducing the healthcare burden (emergency visits, avoidable hospitalisations, disability and costs) while improving quality of life. In the longer term, the incidence of disease may be reduced by innovative prevention strategies. AIRWAYSICPs was initiated by Area 5 of the Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing. All stakeholders are involved (health and social care, patients, and policy makers). PMID:24925919

  1. Paediatric airway management: What is new?

    PubMed Central

    Ramesh, S; Jayanthi, R; Archana, SR

    2012-01-01

    Airway management plays a pivotal role in Paediatric Anaesthesia. Over the last two decades many improvements in this area have helped us to overcome this final frontier. From an era where intubation with a conventional laryngoscope or blind nasal intubation was the only tool for airway management, we have come a long way. Today supraglottic airway devices have pride of place in the Operating Room and are becoming important airway devices used in routine procedures. Direct and indirect fibreoptic laryngoscopes and transtracheal devices help us overcome difficult and previously impossible airway situations. These developments mean that we need to update our knowledge on these devices. Also much of our basic understanding of the physiology and anatomy of the paediatric airway has changed. This article attempts to shed light on some of the most important advances/opinions in paediatric airway management like, cuffed endotracheal tubes, supraglottic airway devices, video laryngoscopes, rapid sequence intubation, the newly proposed algorithm for difficult airway management and the role of Ex Utero Intrapartum Treatment (EXIT) procedure in the management of the neonatal airway. PMID:23293383

  2. Palliative Airway Stenting Performed Under Radiological Guidance and Local Anesthesia

    SciTech Connect

    Profili, Stefano; Manca, Antonio; Feo, Claudio F. Padua, Guglielmo; Ortu, Riccardo; Canalis, Giulio C.; Meloni, Giovanni B.

    2007-02-15

    Purpose. To assess the effectiveness of airway stenting performed exclusively under radiological guidance for the palliation of malignant tracheobronchial strictures. Methods. We report our experience in 16 patients with malignant tracheobronchial stricture treated by insertion of 20 Ultraflex self-expandable metal stents performed under fluoroscopic guidance only. Three patients presented dysphagia grade IV due to esophageal malignant infiltration; they therefore underwent combined airway and esophageal stenting. All the procedures were performed under conscious sedation in the radiological room; average procedure time was around 10 min, but the airway impediment never lasted more than 40 sec. Results. We obtained an overall technical success in 16 cases (100%) and clinical success in 14 patients (88%). All prostheses were successfully placed without procedural complications. Rapid clinical improvement with symptom relief and normalization of respiratory function was obtained in 14 cases. Two patients died within 48 hr from causes unrelated to stent placement. Two cases (13%) of migration were observed; they were successfully treated with another stent. Tumor overgrowth developed in other 2 patients (13%); however, no further treatment was possible because of extensive laryngeal infiltration. Conclusions. Tracheobronchial recanalization with self-expandable metal stents is a safe and effective palliative treatment for malignant strictures. Airway stenting performed exclusively under fluoroscopic view was rapid and well tolerated.

  3. ICOS ligand expression is essential for allergic airway hyperresponsiveness.

    PubMed

    Kadkhoda, Kamran; Wang, Shuhe; Fan, Yijun; Qiu, Hongyu; Basu, Sujata; Halayko, Andrew J; Yang, Xi

    2011-04-01

    Inducible co-stimulator ligand (ICOSL) is a rather newly defined co-stimulatory molecule, which, through interaction with ICOS expressed on T cells, plays an important role in T-cell activation, differentiation and function. T(h)2-type immune responses are critical for the development and maintenance of allergic responses including asthma. Using knockout (KO) mice, we have assessed the role of ICOSL in allergic airway inflammation and responsiveness using a standard mouse asthma model induced by ovalbumin (OVA) sensitization and challenge. Our data show that OVA-treated ICOSL KO mice exhibit significantly less lung eosinophilic infiltration, histopathology, mucus production and virtually no airway hyperresponsiveness in contrast to wild-type (Wt) counterparts. Serum antibody analysis showed that antigen-specific IgG1, IgG2a and IgE titers in ICOSL KO mice were significantly lower than those of Wt controls. Also, CD4(+) T cells isolated from ICOSL KO mice produced less T(h)2 cytokines (IL-4, IL-5, IL-10 and IL-13) but more T(h)1 (IFN-γ) and IL-17 than their Wt controls. Taken together, we conclude that ICOSL plays an important role in predisposing individuals to allergic airway hyperresponsiveness by enhancing IgE antibody class switching and T(h)2 cytokine production and diminishing the T(h)17 response and airway eosinophilia. PMID:21402623

  4. Environmental factors altering thyroid function and their assessment.

    PubMed Central

    Barsano, C P

    1981-01-01

    Chronic ingestion of modest doses of dietary iodine, radiation, and polyhalogenated biphenyls (PCB's and PBB's) are environmental factors with known or suspected adverse effects on the human thyroid. Iodine consumption in the United States is approaching 1 mg daily for a large segment of the population. Data are reviewed which support the need for concern regarding the long-term adverse effects of dietary iodine on thyroid function, particularly in certain susceptible individuals. Environmental sources of radiation pose a significant risk of thyroid cancer and hypothyroidism under certain circumstances which may be intentional, inadvertent, or accidental. Exposure to polyhalogenated biphenyls during manufacture or as industrial pollutants are hazardous to man and to wildlife in moderate or large quantities and perhaps also in small amounts. The need to investigate the potential harm posed by these factors in the quantities commonly encountered is emphasized. PMID:6263611

  5. Correction factors for assessing immersion suits under harsh conditions.

    PubMed

    Power, Jonathan; Tikuisis, Peter; Ré, António Simões; Barwood, Martin; Tipton, Michael

    2016-03-01

    Many immersion suit standards require testing of thermal protective properties in calm, circulating water while these suits are typically used in harsher environments where they often underperform. Yet it can be expensive and logistically challenging to test immersion suits in realistic conditions. The goal of this work was to develop a set of correction factors that would allow suits to be tested in calm water yet ensure they will offer sufficient protection in harsher conditions. Two immersion studies, one dry and the other with 500 mL of water within the suit, were conducted in wind and waves to measure the change in suit insulation. In both studies, wind and waves resulted in a significantly lower immersed insulation value compared to calm water. The minimum required thermal insulation for maintaining heat balance can be calculated for a given mean skin temperature, metabolic heat production, and water temperature. Combining the physiological limits of sustainable cold water immersion and actual suit insulation, correction factors can be deduced for harsh conditions compared to calm. The minimum in-situ suit insulation to maintain thermal balance is 1.553-0.0624·TW + 0.00018·TW(2) for a dry calm condition. Multiplicative correction factors to the above equation are 1.37, 1.25, and 1.72 for wind + waves, 500 mL suit wetness, and both combined, respectively. Calm water certification tests of suit insulation should meet or exceed the minimum in-situ requirements to maintain thermal balance, and correction factors should be applied for a more realistic determination of minimum insulation for harsh conditions. PMID:26674408

  6. Intubations and airway management: An overview of Hassles through third millennium

    PubMed Central

    Alanazi, Abdullah

    2015-01-01

    Background: The placement of a tube into a patient's trachea “the intubation” as we call is not as simple as it looks. It is a very tricky and tedious maneuver that entails skills to assess and perform. Nevertheless, often this is left to the chores of inefficient hands due to a paucity of the availability of experts. They seldom are able to complete the task and often wind up calling the attention of the unit. The present review is an attempt to describe the need to undertake intubation, the procedures and techniques, the complications, including morbidity and mortality and airway management. This overview includes explicit descriptions of the difficult airway which represents multifaceted interface amid patient factors, clinical setting, and skills of the practitioner. Materials and Methods: To accomplish the target, peer-reviewed English language articles published during third millennium up to 2013 were selected from Pub Med, Pub Med Central, Science Direct, Up-to-date, Med Line, comprehensive databases, Cochrane library, and the Internet (Google, Yahoo). Review of Literature: The review constituted a systematic search of literature on the requirements that necessitate the practice of intubation, different techniques that facilitate easy conduct of procedure, the complications, including, morbidity and mortality, and the airway management. Conclusion: Recording every single detail has been beyond the scope of this review, however; some aspects have been wrapped up in nutshell. Some areas of the review are too basic which the medics are well aware of and knowledgeable. Nevertheless, these are difficult to be dispensed with in consideration of their source to the awareness of a common man and a great majority of the patients. PMID:25949040

  7. Quantitative computed tomography–derived clusters: Redefining airway remodeling in asthmatic patients☆

    PubMed Central

    Gupta, Sumit; Hartley, Ruth; Khan, Umair T.; Singapuri, Amisha; Hargadon, Beverly; Monteiro, William; Pavord, Ian D.; Sousa, Ana R.; Marshall, Richard P.; Subramanian, Deepak; Parr, David; Entwisle, James J.; Siddiqui, Salman; Raj, Vimal; Brightling, Christopher E.

    2014-01-01

    Background Asthma heterogeneity is multidimensional and requires additional tools to unravel its complexity. Computed tomography (CT)–assessed proximal airway remodeling and air trapping in asthmatic patients might provide new insights into underlying disease mechanisms. Objectives The aim of this study was to explore novel, quantitative, CT-determined asthma phenotypes. Methods Sixty-five asthmatic patients and 30 healthy subjects underwent detailed clinical, physiologic characterization and quantitative CT analysis. Factor and cluster analysis techniques were used to determine 3 novel, quantitative, CT-based asthma phenotypes. Results Patients with severe and mild-to-moderate asthma demonstrated smaller mean right upper lobe apical segmental bronchus (RB1) lumen volume (LV) in comparison with healthy control subjects (272.3 mm3 [SD, 112.6 mm3], 259.0 mm3 [SD, 53.3 mm3], 366.4 mm3 [SD, 195.3 mm3], respectively; P = .007) but no difference in RB1 wall volume (WV). Air trapping measured based on mean lung density expiratory/inspiratory ratio was greater in patients with severe and mild-to-moderate asthma compared with that seen in healthy control subjects (0.861 [SD, 0.05)], 0.866 [SD, 0.07], and 0.830 [SD, 0.06], respectively; P = .04). The fractal dimension of the segmented airway tree was less in asthmatic patients compared with that seen in control subjects (P = .007). Three novel, quantitative, CT-based asthma clusters were identified, all of which demonstrated air trapping. Cluster 1 demonstrates increased RB1 WV and RB1 LV but decreased RB1 percentage WV. On the contrary, cluster 3 subjects have the smallest RB1 WV and LV values but the highest RB1 percentage WV values. There is a lack of proximal airway remodeling in cluster 2 subjects. Conclusions Quantitative CT analysis provides a new perspective in asthma phenotyping, which might prove useful in patient selection for novel therapies. PMID:24238646

  8. miR-125b inhibits goblet cell differentiation in allergic airway inflammation by targeting SPDEF.

    PubMed

    Liu, Zhaoe; Chen, Xing; Wu, Qiaoling; Song, Jia; Wang, Lijun; Li, Gang

    2016-07-01

    Asthma is a disease characterized by goblet cell differentiation, mucus hypersecretion, airway inflammation, and airway hyperresponsiveness. miR-125b was downregulated as normal human bronchial epithelial cells differentiation to pseudostratified epithelium. However, its role in asthma remains unknown especially in regulating goblet cell differentiation. miR-125b expression in the sputum of 50 asthmatic children and 50 age- and sex-matched healthy controls were assessed by quantitative RT-PCR (qRT-PCR). Meanwhile, expressions of miR-125b and SAM pointed domain-containing ETS transcription factor (SPDEF) in normal human tracheal epithelial (HTEpC) and A549 cells stimulated with lipopolysaccharide (LPS) for 2h were detected by qRT-PCR and western blot. Furthermore, the predicted miR-125b target was determined in silico and confirmed with dual-luciferase reporter assay. Additionally, intranasal delivery of miR-125b mimic in mice was performed to study its effects on house dust mite-induced allergic airway inflammation mouse models. We found that miR-125b expression was decreased in the sputum of the asthmatic patients especially in eosinophilic asthma. After stimulation with LPS, miR-125b expression was downregulated, accompanied by the upregulation of SPDEF in HTEpC and A549 cells. Moreover, SPDEF is a target of miR-125b, which regulates SPDEF at the posttranscriptional level. Additionally, intranasal delivery of miR-125b decreased SPDEF protein levels, goblet cell differentiation, mucus hypersecretion, and altered relevant gene expressions. Taken together, these results suggest that miR-125b inhibits SPDEF expression modulating goblet cell differentiation and mucus secretion in asthma. PMID:27112664

  9. Clinical predictors of central sleep apnea evoked by positive airway pressure titration

    PubMed Central

    Moro, Marilyn; Gannon, Karen; Lovell, Kathy; Merlino, Margaret; Mojica, James; Bianchi, Matt T

    2016-01-01

    Purpose Treatment-emergent central sleep apnea (TECSA), also called complex apnea, occurs in 5%–15% of sleep apnea patients during positive airway pressure (PAP) therapy, but the clinical predictors are not well understood. The goal of this study was to explore possible predictors in a clinical sleep laboratory cohort, which may highlight those at risk during clinical management. Methods We retrospectively analyzed 728 patients who underwent PAP titration (n=422 split-night; n=306 two-night). Demographics and self-reported medical comorbidities, medications, and behaviors as well as standard physiological parameters from the polysomnography (PSG) data were analyzed. We used regression analysis to assess predictors of binary presence or absence of central apnea index (CAI) ≥5 during split-night PSG (SN-PSG) versus full-night PSG (FN-PSG) titrations. Results CAI ≥5 was present in 24.2% of SN-PSG and 11.4% of FN-PSG patients during titration. Male sex, maximum continuous positive airway pressure, and use of bilevel positive airway pressure were predictors of TECSA, and rapid eye movement dominance was a negative predictor, for both SN-PSG and FN-PSG patients. Self-reported narcotics were a positive predictor of TECSA, and the time spent in stage N2 sleep was a negative predictor only for SN-PSG patients. Self-reported history of stroke and the CAI during the diagnostic recording predicted TECSA only for FN-PSG patients. Conclusion Clinical predictors of treatment-evoked central apnea spanned demographic, medical history, sleep physiology, and titration factors. Improved predictive models may be increasingly important as diagnostic and therapeutic modalities move away from the laboratory setting, even as PSG remains the gold standard for characterizing primary central apnea and TECSA. PMID:27555802

  10. Interstitial pneumonitis after bone marrow transplantation. Assessment of risk factors

    SciTech Connect

    Weiner, R.S.; Bortin, M.M.; Gale, R.P.; Gluckman, E.; Kay, H.E.; Kolb, H.J.; Hartz, A.J.; Rimm, A.A.

    1986-02-01

    Data from 932 patients with leukemia who received bone marrow transplants were analyzed to determine factors associated with an increased risk of developing interstitial pneumonitis. Interstitial pneumonitis developed in 268 patients for a 2-year actuarial incidence of 35 +/- 4% (SD) and with a mortality rate of 24%. Six factors were associated with an increased risk: use of methotrexate rather than cyclosporine after transplantation (relative risk, 2.3; p less than 0.0002); older age (relative risk, 2.1; p less than 0.0001); presence of severe graft-versus-host disease (relative risk, 1.9; p less than 0.003); long interval from diagnosis to transplantation (relative risk, 1.6; p less than 0.002); performance ratings before transplantation of less than 100% (relative risk, 2.1; p less than 0.0001); and high dose-rates of irradiation in patients given methotrexate after transplantation (relative risk, 3.2; p less than 0.03). The risk of developing interstitial pneumonitis ranged from 8% in patients with none of these adverse risk factors to 94% in patients with all six. These findings may help to identify patients at high risk for this complication.

  11. Questionnaire Based Assessment of Risk Factors for Primary Biliary Cirrhosis

    PubMed Central

    Lammert, Craig; Nguyen, Douglas L.; Juran, Brian D.; Schlicht, Erik; Larson, Joseph J.; Atkinson, Elizabeth J.; Lazaridis, Konstantinos N.

    2013-01-01

    Background Primary Biliary Cirrhosis is a cholestatic liver disease characterized by immune-mediated destruction of bile ducts. Its pathogenesis is largely unknown, although complex interactions between environment and genetic predisposition are proposed. Aims Identify disease risk factors using a detailed patient questionnaire and compare study findings to 3 published reports. Methods Questionnaire data were prospectively collected from 522 cases and 616 controls of the Mayo Clinic Primary Biliary Cirrhosis Genetic Epidemiology Registry. Case and control responses were compared using logistic regression, adjusting for recruitment age, sex, and education level. Results Cases reported ever regularly smoking cigarettes more frequently than controls (P < 0.001). History of urinary tract infection (UTI) was similar between groups; however, cases reported multiple UTIs more commonly than controls (P < 0.001). Frequency of other autoimmune disease was higher in cases than controls (P < 0.001). As well, prevalence of primary biliary cirrhosis among first-degree relatives was higher in case families than control families (P < 0.001). Conclusions Our study confirms prior reported risk factors associated with disease risk. Given the potential importance of gene and environment interactions, further examination of environmental risk factors considering genetic background may provide new insight into primary biliary cirrhosis pathogenesis. PMID:23490343

  12. Repurposing tromethamine as inhaled therapy to treat CF airway disease

    PubMed Central

    Abou Alaiwa, Mahmoud H.; Launspach, Janice L.; Sheets, Kelsey A.; Rivera, Jade A.; Gansemer, Nicholas D.; Taft, Peter J.; Thorne, Peter S.; Welsh, Michael J.; Stoltz, David A.; Zabner, Joseph

    2016-01-01

    In cystic fibrosis (CF), loss of CF transmembrane conductance regulator (CFTR) anion channel activity causes airway surface liquid (ASL) pH to become acidic, which impairs airway host defenses. One potential therapeutic approach is to correct the acidic pH in CF airways by aerosolizing HCO3− and/or nonbicarbonate pH buffers. Here, we show that raising ASL pH with inhaled HCO3− increased pH. However, the effect was transient, and pH returned to baseline values within 30 minutes. Tromethamine (Tham) is a buffer with a long serum half-life used as an i.v. formulation to treat metabolic acidosis. We found that Tham aerosols increased ASL pH in vivo for at least 2 hours and enhanced bacterial killing. Inhaled hypertonic saline (7% NaCl) is delivered to people with CF in an attempt to promote mucus clearance. Because an increased ionic strength inhibits ASL antimicrobial factors, we added Tham to hypertonic saline and applied it to CF sputum. We found that Tham alone and in combination with hypertonic saline increased pH and enhanced bacterial killing. These findings suggest that aerosolizing the HCO3−-independent buffer Tham, either alone or in combination with hypertonic saline, might be of therapeutic benefit in CF airway disease. PMID:27390778

  13. Characterizing adult human nasal airway dimensions

    SciTech Connect

    Guilmette, R.A.; Griffith, W.C.

    1994-11-01

    Respiratory tract models used in calculating radiation dose from exposure to inhaled radioactive aerosols have only recently focused attention on the importance of the nasal airways (NAs). Because the NAs are the first tissues of the respiratory tract available for aerosol deposition in normally nose-breathing people, any deposition of aerosol in this anatomical structure will reduce the amounts available to be deposited in the remainder of the respiratory tract. Thus, uncertainties in estimating the deposition fractions in the NAs will propagate throughout the remainder of the respiratory tract, creating errors in the calculated dose estimates. Additionally, there is evidence that the NAs are also at risk for induction of cancer from exposure to certain occupational aerosols such as wood dust, leather dust, chromium, and nickel. The purpose of this investigation was to conduct an anatomical study to assess the variabilities in NA dimensions.

  14. Concomitant exposure to ovalbumin and endotoxin augments airway inflammation but not airway hyperresponsiveness in a murine model of asthma.

    PubMed

    Mac Sharry, John; Shalaby, Karim H; Marchica, Cinzia; Farahnak, Soroor; Chieh-Li, Tien; Lapthorne, Susan; Qureshi, Salman T; Shanahan, Fergus; Martin, James G

    2014-01-01

    Varying concentrations of lipopolysaccharide (LPS) in ovalbumin (OVA) may influence the airway response to allergic sensitization and challenge. We assessed the contribution of LPS to allergic airway inflammatory responses following challenge with LPS-rich and LPS-free commercial OVA. BALB/c mice were sensitized with LPS-rich OVA and alum and then underwent challenge with the same OVA (10 µg intranasally) or an LPS-free OVA. Following challenge, bronchoalveolar lavage (BAL), airway responsiveness to methacholine and the lung regulatory T cell population (Treg) were assessed. Both OVA preparations induced BAL eosinophilia but LPS-rich OVA also evoked BAL neutrophilia. LPS-free OVA increased interleukin (IL)-2, IL-4 and IL-5 whereas LPS-rich OVA additionally increased IL-1β, IL-12, IFN-γ, TNF-α and KC. Both OVA-challenged groups developed airway hyperresponsiveness. TLR4-deficient mice challenged with either OVA preparation showed eosinophilia but not neutrophilia and had increased IL-5. Only LPS-rich OVA challenged mice had increased lung Tregs and LPS-rich OVA also induced in vitro Treg differentiation. LPS-rich OVA also induced a Th1 cytokine response in human peripheral blood mononuclear cells.We conclude that LPS-rich OVA evokes mixed Th1, Th2 and innate immune responses through the TLR-4 pathway, whereas LPS-free OVA evokes only a Th2 response. Contaminating LPS is not required for induction of airway hyperresponsiveness but amplifies the Th2 inflammatory response and is a critical mediator of the neutrophil, Th1 and T regulatory cell responses to OVA. PMID:24968337

  15. Concomitant Exposure to Ovalbumin and Endotoxin Augments Airway Inflammation but Not Airway Hyperresponsiveness in a Murine Model of Asthma

    PubMed Central

    Mac Sharry, John; Shalaby, Karim H.; Marchica, Cinzia; Farahnak, Soroor; Chieh-Li, Tien; Lapthorne, Susan; Qureshi, Salman T.; Shanahan, Fergus; Martin, James G.

    2014-01-01

    Varying concentrations of lipopolysaccharide (LPS) in ovalbumin (OVA) may influence the airway response to allergic sensitization and challenge. We assessed the contribution of LPS to allergic airway inflammatory responses following challenge with LPS-rich and LPS-free commercial OVA. BALB/c mice were sensitized with LPS-rich OVA and alum and then underwent challenge with the same OVA (10 µg intranasally) or an LPS-free OVA. Following challenge, bronchoalveolar lavage (BAL), airway responsiveness to methacholine and the lung regulatory T cell population (Treg) were assessed. Both OVA preparations induced BAL eosinophilia but LPS-rich OVA also evoked BAL neutrophilia. LPS-free OVA increased interleukin (IL)-2, IL-4 and IL-5 whereas LPS-rich OVA additionally increased IL-1β, IL-12, IFN-γ, TNF-α and KC. Both OVA-challenged groups developed airway hyperresponsiveness. TLR4-deficient mice challenged with either OVA preparation showed eosinophilia but not neutrophilia and had increased IL-5. Only LPS-rich OVA challenged mice had increased lung Tregs and LPS-rich OVA also induced in vitro Treg differentiation. LPS-rich OVA also induced a Th1 cytokine response in human peripheral blood mononuclear cells.We conclude that LPS-rich OVA evokes mixed Th1, Th2 and innate immune responses through the TLR-4 pathway, whereas LPS-free OVA evokes only a Th2 response. Contaminating LPS is not required for induction of airway hyperresponsiveness but amplifies the Th2 inflammatory response and is a critical mediator of the neutrophil, Th1 and T regulatory cell responses to OVA. PMID:24968337

  16. Airway anastomosis for lung transplantation

    PubMed Central

    Diso, Daniele; Rendina, Erino Angelo; Venuta, Federico

    2016-01-01

    Lung transplantation (LT) is the only viable option for a selected group of patients with end stage pulmonary diseases. During the recent years satisfactory results in terms of long-term survival and quality of life have been achieved with improvements in surgical technique, immunosuppression and perioperative management. Since the beginning, the airway anastomosis has been considered crucial and significant efforts have been made to understand the healing process. A number of experimental studies allowed improving the surgical technique by modifying the technique of suturing, the anastomotic protection and type and dose of immunosuppression, reducing the risk of airway complications. Furthermore, a huge progress has been made in the management of such complications. Early diagnosis of bronchial complications and their prompt and correct management are crucial to achieve long-term survival. PMID:26981271

  17. Encountering unexpected difficult airway: relationship with the intubation difficulty scale

    PubMed Central

    Koh, Wonuk; Kim, Hajung; Kim, Kyongsun; Ro, Young-Jin

    2016-01-01

    Background An unexpected difficult intubation can be very challenging and if it is not managed properly, it may expose the encountered patient to significant risks. The intubation difficulty scale (IDS) has been used as a validated method to evaluate a global degree of intubation difficulty. The aims of this study were to evaluate the prevalence and characteristics of unexpected difficult intubation using the IDS. Methods We retrospectively reviewed 951 patients undergoing elective surgery in a single medical center. Patients expected to have a difficult intubation or who had history of difficult intubation were excluded. Each patient was assessed by the IDS scoring system with seven variables. Total prevalence of difficult intubation and the contributing individual factors were further analyzed. Results For the 951 patients, the difficult intubation cases presenting IDS > 5 was 5.8% of total cases (n = 55). The prevalence of Cormack-Lehane Grade 3 or 4 was 16.2% (n = 154). Most of the difficult intubation cases were managed by simple additional maneuvers and techniques such as stylet application, additional lifting force and laryngeal pressure. Conclusions Unexpected difficult airway was present in 5.8% of patients and most was managed effectively. Among the components of IDS, the Cormack-Lehane grade was most sensitive for predicting difficult intubation. PMID:27274369

  18. A Persistent and Diverse Airway Microbiota Present during Chronic Obstructive Pulmonary Disease Exacerbations

    PubMed Central

    Huang, Yvonne J.; Kim, Eugenia; Cox, Michael J.; Brodie, Eoin L.; Brown, Ron; Wiener-Kronish, Jeanine P.

    2010-01-01

    Abstract Acute exacerbations of chronic obstructive pulmonary disease (COPD) are a major source of morbidity and contribute significantly to healthcare costs. Although bacterial infections are implicated in nearly 50% of exacerbations, only a handful of pathogens have been consistently identified in COPD airways, primarily by culture-based methods, and the bacterial microbiota in acute exacerbations remains largely uncharacterized. The aim of this study was to comprehensively profile airway bacterial communities using a culture-independent microarray, the 16S rRNA PhyloChip, of a cohort of COPD patients requiring ventilatory support and antibiotic therapy for exacerbation-related respiratory failure. PhyloChip analysis revealed the presence of over 1,200 bacterial taxa representing 140 distinct families, many previously undetected in airway diseases; bacterial community composition was strongly influenced by the duration of intubation. A core community of 75 taxa was detected in all patients, many of which are known pathogens. Bacterial community diversity in COPD airways is substantially greater than previously recognized and includes a number of potential pathogens detected in the setting of antibiotic exposure. Comprehensive assessment of the COPD airway microbiota using high-throughput, culture-independent methods may prove key to understanding the relationships between airway bacterial colonization, acute exacerbation, and clinical outcomes in this and other chronic inflammatory airway diseases. PMID:20141328

  19. Airway management and postoperative length of hospital stay in patients undergoing head and neck cancer surgery

    PubMed Central

    Siddiqui, Ali Sarfraz; Dogar, Samie Asghar; Lal, Shankar; Akhtar, Shabbir; Khan, Fauzia Anis

    2016-01-01

    Background and Aims: General anesthesia and airway management of patients for head and neck cancer surgery is a challenge for the anesthesiologist. Appropriate assessment and planning are essential for successful airway management. Our objectives were to review airway management strategies in patients undergoing head and neck cancer surgery in our tertiary care institution and also to observe the effect of airway management techniques on postoperative length of hospital stay (PLOS). Material and Methods: A retrospective medical record review of 400 patients who underwent major head and neck cancer surgery in our institution was conducted. A special form was used, and records were searched for airway and anesthetic management in the operating room and recovery room, and for PLOS. Results: 289 (72.25%) of the patients were male, and 111 (27.75%) female. 49.8% of patients had Mallampati score of 3 and 4. Airway was managed with tracheostomy in 81 (20.25%) patients; nasal intubation was performed in 177 (44.25%) and oral intubation in 142 (35.5%) patients. Postoperative emergency tracheostomy was not done in any of the patients. Conclusion: Median postoperative hospital stay was significantly longer (P = 0.0005) in patients who had a tracheostomy performed compared with those where the airway was managed without it. PMID:27006541

  20. Liquid and surfactant delivery into pulmonary airways

    PubMed Central

    Halpern, David; Fujioka, Hideki; Takayama, Shuichi; Grotberg, James B.

    2008-01-01

    We describe the mechanisms by which liquids and surfactants can be delivered into the pulmonary airways. These are instilled and transported throughout the lung in clinical therapies such as surfactant replacement therapy, partial liquid ventilation and drug delivery. The success of these treatments is contingent on the liquid distribution and the delivery to targeted regions of the lung. The targeting of a liquid plug can be influenced by a variety of factors such as the physical properties of the liquid, the interfacial activity, the gravitational orientation, instillation method and propagation speed. We provide a review of experimental and theoretical studies that examine these effects in single tubes or channels, in tubes with single bifurcations and in the whole lung. PMID:18585985

  1. Partial airway obstruction following manufacturing defect in laryngeal mask airway (Laryngeal Mask Silken™).

    PubMed

    Jangra, Kiran; Malhotra, Surender Kumar; Saini, Vikas

    2014-10-01

    Laryngeal mask (LM) airway is commonly used for securing airway in day-care surgeries. Various problems have been described while using LM airway. Out of those, mechanical obstruction causing airway compromise is most common. Here, we describe a case report of 4-year-old child who had partial upper airway obstruction due to LM manufacturer's defect. There was a silicon band in upper one-third of shaft of LM airway. This band was made up of the same material as that of LM airway so it was not identifiable on external inspection of transparent shaft. We suggest that such as non-transparent laryngeal mask, a transparent LM airway should also be inspected looking inside the lumen with naked eyes or by using a probe to rule out any manufacturing defect before its insertion. PMID:25422617

  2. Pericytes contribute to airway remodeling in a mouse model of chronic allergic asthma.

    PubMed

    Johnson, Jill R; Folestad, Erika; Rowley, Jessica E; Noll, Elisa M; Walker, Simone A; Lloyd, Clare M; Rankin, Sara M; Pietras, Kristian; Eriksson, Ulf; Fuxe, Jonas

    2015-04-01

    Myofibroblast accumulation, subepithelial fibrosis, and vascular remodeling are complicating features of chronic asthma, but the mechanisms are not clear. Platelet-derived growth factors (PDGFs) regulate the fate and function of various mesenchymal cells and have been implicated as mediators of lung fibrosis. However, it is not known whether PDGF-BB signaling via PDGFRβ, which is critical for the recruitment of pericytes to blood vessels, plays a role in airway remodeling in chronic asthma. In the present study, we used a selective PDGFRβ inhibitor (CP-673451) to investigate the role of PDGFRβ signaling in the development of airway remodeling and lung dysfunction in an established mouse model of house dust mite-induced chronic allergic asthma. Unexpectedly, we found that pharmacological inhibition of PDGFRβ signaling in the context of chronic aeroallergen exposure led to exacerbated lung dysfunction and airway smooth muscle thickening. Further studies revealed that the inflammatory response to aeroallergen challenge in mice was associated with decreased PDGF-BB expression and the loss of pericytes from the airway microvasculature. In parallel, cells positive for pericyte markers accumulated in the subepithelial region of chronically inflamed airways. This process was exacerbated in animals treated with CP-673451. The results indicate that perturbed PDGF-BB/PDGFRβ signaling and pericyte accumulation in the airway wall may contribute to airway remodeling in chronic allergic asthma. PMID:25637607