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Sample records for airway extraluminal tissue

  1. Airway tissue engineering for congenital laryngotracheal disease.

    PubMed

    Maughan, Elizabeth; Lesage, Flore; Butler, Colin R; Hynds, Robert E; Hewitt, Richard; Janes, Sam M; Deprest, Jan A; Coppi, Paolo De

    2016-06-01

    Regenerative medicine offers hope of a sustainable solution for severe airway disease by the creation of functional, immunocompatible organ replacements. When considering fetuses and newborns, there is a specific spectrum of airway pathologies that could benefit from cell therapy and tissue engineering applications. While hypoplastic lungs associated with congenital diaphragmatic hernia (CDH) could benefit from cellular based treatments aimed at ameliorating lung function, patients with upper airway obstruction could take advantage from a de novo tissue engineering approach. Moreover, the international acceptance of the EXIT procedure as a means of securing the precarious neonatal airway, together with the advent of fetal surgery as a method of heading off postnatal co-morbidities, offers the revolutionary possibility of extending the clinical indication for tissue-engineered airway transplantation to infants affected by diverse severe congenital laryngotracheal malformations. This article outlines the necessary basic components for regenerative medicine solutions in this potential clinical niche. PMID:27301606

  2. Extraluminal factors contributing to inflammatory bowel disease

    PubMed Central

    Batra, Arvind; Stroh, Thorsten; Siegmund, Britta

    2011-01-01

    Many identified and yet unknown factors contribute to the pathogenesis of inflammatory bowel disease (IBD). The genome-wide association studies clearly support the earlier developed concept that IBD occurs in genetically predisposed individuals who are exposed to distinct environmental factors, which together result in dysregulation of the mucosal immune system. Thus, the majority of previous studies have focused on the immune response within the intestinal wall. The present review aims to emphasize the contribution of three extraluminal structures to this inflammatory process, namely the mesenteric fat tissue, the lymphatics and the microvasculature. Broadening our view across the intestinal wall will not only facilitate our understanding of the disease, but will also us to identify future therapeutic targets. PMID:21350706

  3. Tissue Engineered Airways: A Prospects Article.

    PubMed

    Bogan, Stephanie L; Teoh, Gui Zhen; Birchall, Martin A

    2016-07-01

    An ideal tracheal scaffold must withstand luminal collapse yet be flexible, have a sufficient degree of porosity to permit vascular and cellular ingrowth, but also be airtight and must facilitate growth of functional airway epithelium to avoid infection and aid in mucocilliary clearance. Finally, the scaffold must also be biocompatible to avoid implant rejection. Over the last 40 years, efforts to design and manufacture the airway have been undertaken worldwide but success has been limited and far apart. As a result, tracheal resection with primary repair remains the Gold Standard of care for patients presenting with airway disorders and malignancies. However, the maximum resectable length of the trachea is restricted to 30% of the total length in children or 50% in adults. Attempts to provide autologous grafts for human application have also been disappointing for a host of different reasons, including lack of implant integration, insufficient donor organs, and poor mechanical strength resulting in an unmet clinical need. The two main approaches researchers have taken to address this issue have been the development of synthetic scaffolds and the use of decellularized organs. To date, a number of different decellularization techniques and a variety of materials, including polyglycolic acid (PGA) and nanocomposite polymers have been explored. The findings thus far have shown great promise, however, there remain a significant number of caveats accompanying each approach. That being said, the possibilities presented by these two approaches could be combined to produce a highly successful, clinically viable hybrid scaffold. This article aims to highlight advances in airway tissue engineering and provide an overview of areas to explore and utilize in accomplishing the aim of developing an ideal tracheal prosthesis. J. Cell. Biochem. 117: 1497-1505, 2016. © 2016 Wiley Periodicals, Inc. PMID:26853803

  4. Tissue Inhibitor of Metalloproteinase-1 Moderates Airway Re-Epithelialization by Regulating Matrilysin Activity

    PubMed Central

    Chen, Peter; McGuire, John K.; Hackman, Robert C.; Kim, Kyoung-Hee; Black, Roy A.; Poindexter, Kurt; Yan, Wei; Liu, Phillip; Chen, Ann J.; Parks, William C.; Madtes, David K.

    2008-01-01

    Obliterative bronchiolitis (OB) is the histopathological finding in chronic lung allograft rejection. Mounting evidence suggests that epithelial damage drives the development of airway fibrosis in OB. Tissue inhibitor of metalloproteinase (TIMP)-1 expression increases in lung allografts and is associated with the onset of allograft rejection. Furthermore, in a mouse model of OB, airway obliteration is reduced in TIMP-1-deficient mice. Matrilysin (matrix metallproteinase-7) is essential for airway epithelial repair and is required for the re-epithelialization of airway wounds by facilitating cell migration; therefore, the goal of this study was to determine whether TIMP-1 inhibits re-epithelialization through matrilysin. We found that TIMP-1 and matrilysin co-localized in the epithelium of human lungs with OB and both co-localized and co-immunoprecipitated in wounded primary airway epithelial cultures. TIMP-1-deficient cultures migrated faster, and epithelial cells spread to a greater extent compared with wild-type cultures. TIMP-1 also inhibited matrilysin-mediated cell migration and spreading in vitro. In vivo, TIMP-1 deficiency enhanced airway re-epithelialization after naphthalene injury. Furthermore, TIMP-1 and matrilysin co-localized in airway epithelial cells adjacent to the wound edge. Our data demonstrate that TIMP-1 interacts with matrix metalloproteinases and regulates matrilysin activity during airway epithelial repair. Furthermore, we speculate that TIMP-1 overexpression restricts airway re-epithelialization by inhibiting matrilysin activity, contributing to a stereotypic injury response that promotes airway fibrosis via bronchiole airway epithelial damage and obliteration. PMID:18385523

  5. Evaluation of magnesium-yttrium alloy as an extraluminal tracheal stent.

    PubMed

    Luffy, Sarah A; Chou, Da-Tren; Waterman, Jenora; Wearden, Peter D; Kumta, Prashant N; Gilbert, Thomas W

    2014-03-01

    Tracheomalacia is a relatively rare problem, but can be challenging to treat, particularly in pediatric patients. Due to the presence of mechanically deficient cartilage, the trachea is unable to resist collapse under physiologic pressures of respiration, which can lead to acute death if left untreated. However, if treated, the outcome for patients with congenital tracheomalacia is quite good because the cartilage tends to spontaneously mature over a period of 12 to 18 months. The present study investigated the potential for the use of degradable magnesium-3% yttrium alloy (W3) to serve as an extraluminal tracheal stent in a canine model. The host response to the scaffold included the formation of a thin, vascularized capsule consisting of collagenous tissue and primarily mononuclear cells. The adjacent cartilage structure was not adversely affected as observed by bronchoscopic, gross, histologic, and mechanical analysis. The W3 stents showed reproducible spatial and temporal fracture patterns, but otherwise tended to corrode quite slowly, with a mix of Ca and P rich corrosion product formed on the surface and observed focal regions of pitting. The study showed that the approach to use degradable magnesium alloys as an extraluminal tracheal stent is promising, although further development of the alloys is required to improve the resistance to stress corrosion cracking and improve the ductility. PMID:23554285

  6. Submental negative pressure application decreases collapsibility of the passive pharyngeal airway in nonobese women.

    PubMed

    Kato, Shinichiro; Isono, Shiroh; Amemiya, Megumi; Sato, Shin; Ikeda, Aya; Okazaki, Junko; Sato, Yumi; Ishikawa, Teruhiko

    2015-04-01

    The pharyngeal airway is surrounded by soft tissues that are also enclosed by bony structures such as the mandible, maxilla, and cervical spine. The passive pharyngeal airway is therefore structurally analogous to a collapsible tube within a rigid box. Cross-sectional area of the tube is determined by transmural pressure, the pressure difference between intraluminal and extraluminal pressures. Due to a lack of knowledge on the influence of extraluminal soft tissue pressure on the human pharyngeal airway patency, we hypothesized that application of negative external pressure to the submental region decreases collapsibility of the passive pharynx, and that obese individuals have less response to the intervention than nonobese individuals. Static mechanical properties of the passive pharynx were compared before and during application of submental negative pressure in 10 obese and 10 nonobese adult women under general anesthesia and paralysis. Negative pressure was applied through use of a silicone collar covering the entire submental region and a vacuum pump. In nonobese subjects, application of submental negative pressure (-25 and -50 cmH2O) significantly decreased closing pressures at the retropalatal airway by 2.3 ± 3.2 cmH2O and 2.0 ± 3.0 cmH2O, respectively, and at the retroglossal airway by 2.9 ± 2.7 cmH2O and 3.7 ± 2.6 cmH2O, respectively, and the intervention stiffened the retroglossal pharyngeal airway wall. No significant mechanical changes were observed during application of submental negative pressure in obese subjects. Conclusively, application of submental negative pressure was found to decreases collapsibility of the passive pharyngeal airway in nonobese Japanese women. PMID:25614595

  7. Autofluorescence multiphoton microscopy for visualization of tissue morphology and cellular dynamics in murine and human airways

    PubMed Central

    Kretschmer, Sarah; Pieper, Mario; Hüttmann, Gereon; Bölke, Torsten; Wollenberg, Barbara; Marsh, Leigh M; Garn, Holger; König, Peter

    2016-01-01

    The basic understanding of inflammatory airway diseases greatly benefits from imaging the cellular dynamics of immune cells. Current imaging approaches focus on labeling specific cells to follow their dynamics but fail to visualize the surrounding tissue. To overcome this problem, we evaluated autofluorescence multiphoton microscopy for following the motion and interaction of cells in the airways in the context of tissue morphology. Freshly isolated murine tracheae from healthy mice and mice with experimental allergic airway inflammation were examined by autofluorescence multiphoton microscopy. In addition, fluorescently labeled ovalbumin and fluorophore-labeled antibodies were applied to visualize antigen uptake and to identify specific cell populations, respectively. The trachea in living mice was imaged to verify that the ex vivo preparation reflects the in vivo situation. Autofluorescence multiphoton microscopy was also tested to examine human tissue from patients in short-term tissue culture. Using autofluorescence, the epithelium, underlying cells, and fibers of the connective tissue, as well as blood vessels, were identified in isolated tracheae. Similar structures were visualized in living mice and in the human airway tissue. In explanted murine airways, mobile cells were localized within the tissue and we could follow their migration, interactions between individual cells, and their phagocytic activity. During allergic airway inflammation, increased number of eosinophil and neutrophil granulocytes were detected that moved within the connective tissue and immediately below the epithelium without damaging the epithelial cells or connective tissues. Contacts between granulocytes were transient lasting 3 min on average. Unexpectedly, prolonged interactions between granulocytes and antigen-uptaking cells were observed lasting for an average of 13 min. Our results indicate that autofluorescence-based imaging can detect previously unknown immune cell

  8. Autofluorescence multiphoton microscopy for visualization of tissue morphology and cellular dynamics in murine and human airways.

    PubMed

    Kretschmer, Sarah; Pieper, Mario; Hüttmann, Gereon; Bölke, Torsten; Wollenberg, Barbara; Marsh, Leigh M; Garn, Holger; König, Peter

    2016-08-01

    The basic understanding of inflammatory airway diseases greatly benefits from imaging the cellular dynamics of immune cells. Current imaging approaches focus on labeling specific cells to follow their dynamics but fail to visualize the surrounding tissue. To overcome this problem, we evaluated autofluorescence multiphoton microscopy for following the motion and interaction of cells in the airways in the context of tissue morphology. Freshly isolated murine tracheae from healthy mice and mice with experimental allergic airway inflammation were examined by autofluorescence multiphoton microscopy. In addition, fluorescently labeled ovalbumin and fluorophore-labeled antibodies were applied to visualize antigen uptake and to identify specific cell populations, respectively. The trachea in living mice was imaged to verify that the ex vivo preparation reflects the in vivo situation. Autofluorescence multiphoton microscopy was also tested to examine human tissue from patients in short-term tissue culture. Using autofluorescence, the epithelium, underlying cells, and fibers of the connective tissue, as well as blood vessels, were identified in isolated tracheae. Similar structures were visualized in living mice and in the human airway tissue. In explanted murine airways, mobile cells were localized within the tissue and we could follow their migration, interactions between individual cells, and their phagocytic activity. During allergic airway inflammation, increased number of eosinophil and neutrophil granulocytes were detected that moved within the connective tissue and immediately below the epithelium without damaging the epithelial cells or connective tissues. Contacts between granulocytes were transient lasting 3 min on average. Unexpectedly, prolonged interactions between granulocytes and antigen-uptaking cells were observed lasting for an average of 13 min. Our results indicate that autofluorescence-based imaging can detect previously unknown immune cell

  9. Partitioning of airway and respiratory tissue mechanical impedances by body plethysmography.

    PubMed

    Peslin, R; Duvivier, C

    1998-02-01

    We have tested the feasibility of separating the airway (Zaw) and tissue (Zti) components of total respiratory input impedance (Zrs,in) in healthy subjects by measuring alveolar gas compression by body plethysmography (Vpl) during pressure oscillations at the airway opening. The forced oscillation set up was placed inside a body plethysmograph, and the subjects rebreathed BTPS gas. Zrs,in and the relationship between Vpl and airway flow (Hpl) were measured from 4 to 29 Hz. Zaw and Zti were computed from Zrs,in and Hpl by using the monoalveolar T-network model and alveolar gas compliance derived from thoracic gas volume. The data were in good agreement with previous observations: airways and tissue resistance exhibited some positive and negative frequency dependences, respectively; airway reactance was consistent with an inertance of 0.015 +/- 0.003 hPa.s2.l-1 and tissue reactance with an elastance of 36 +/- 8 hPa/I. The changes seen with varying lung volume, during elastic loading of the chest and during bronchoconstriction, were mostly in agreement with the expected effects. The data, as well as computer simulation, suggest that the partitioning is unaffected by mechanical inhomogeneity and only moderately affected by airway wall shunting. PMID:9475865

  10. Host-Integration of a Tissue-Engineered Airway Patch: Two-Year Follow-Up in a Single Patient

    PubMed Central

    Dally, Iris; Friedel, Godehard; Walles, Heike; Walles, Thorsten

    2015-01-01

    Different bioengineering techniques have been applied repeatedly for the reconstruction of extensive airway defects in the last few years. While short-term surgical success is evident, there is a lack of long-term results in patients. Here, we report the case of a young male who received a 5×2 cm bioartificial airway patch for tracheoesophageal reconstruction focusing on clinical defect healing and histomorphological tissue reorganization 2.5 years after surgery. We generated bioartificial airway tissue using a cell-free biological vascularized scaffold that was re-endothelialized and reseeded with the recipient's autologous primary cells and we implanted it into the recipient's left main bronchus. To investigate host-integration 2.5 years after the implantation, we obtained biopsies of the implant and adjacent tracheal tissue and processed these for histological and immunohistochemical analyses. The early postoperative course was uneventful and the transplanted airway tissue was integrated into the host. 2.5 years after transplantation, a bronchoscopy confirmed the scar-free reconstruction of the former airway defect. Histological work-up documented respiratory airway mucosa lining the bronchial reconstruction, making it indistinguishable from native airway mucosa. After transplantation, our bioartificial airway tissue provided perfect airway healing, with no histological evidence of tissue dedifferentiation. PMID:25316325

  11. Does the Oropharyngeal Fat Tissue Influence the Oropharyngeal Airway in Snorers? Dynamic CT Study

    PubMed Central

    Akan, Huseyin; Celebi, Mehmet; Sakan, Banu Baglan

    2004-01-01

    Objective The aim of this study was to determine if snorers have a narrower oropharyngeal airway area because of fat infiltration, and an elevated body mass index. Materials and Methods Ten control subjects and 19 patients that snored were evaluated. We obtained 2-mm-thick axial CT scan images every 0.6 seconds during expiration and inspiration at the same level of the oropharynx. We selected the largest and the smallest oropharyngeal airway areas and found the differences. From the slice that had the smallest oropharyngeal airway area, the thickness of the parapharyngeal and subcutaneous fat was measured. The measurements from the left and right side were added together and single values for parapharyngeal and subcutaneous fat tissue thickness were then found. Results The conventional measure of body mass index was significantly higher in the snorers (p < 0.05). The difference in the smallest oropharyngeal airway area between snorers and the controls was statistically significant (p < 0.01). The average difference between the largest and the smallest oropharyngeal area in the control group and the snorer group was statistically significant (p < 0.05). There was no significant difference in the largest oropharyngeal airway area, the total subcutaneous fat width and the total parapharyngeal fat width between snorers and control subjects (p > 0.05). Conclusion We concluded that the oropharyngeal fat deposition in snorers is not an important factor, and it does not predispose a person to the upper airway narrowing. PMID:15235234

  12. Airway Tissue Plasminogen Activator Prevents Acute Mortality Due to Lethal Sulfur Mustard Inhalation

    PubMed Central

    Veress, Livia A.; Anderson, Dana R.; Hendry-Hofer, Tara B.; Houin, Paul R.; Rioux, Jacqueline S.; Garlick, Rhonda B.; Loader, Joan E.; Paradiso, Danielle C.; Smith, Russell W.; Rancourt, Raymond C.; Holmes, Wesley W.; White, Carl W.

    2015-01-01

    Rationale: Sulfur mustard (SM) is a chemical weapon stockpiled today in volatile regions of the world. SM inhalation causes a life-threatening airway injury characterized by airway obstruction from fibrin casts, which can lead to respiratory failure and death. Mortality in those requiring intubation is more than 80%. No therapy exists to prevent mortality after SM exposure. Our previous work using the less toxic analog of SM, 2-chloroethyl ethyl sulfide, identified tissue plasminogen activator (tPA) an effective rescue therapy for airway cast obstruction (Veress, L. A., Hendry-Hofer, T. B., Loader, J. E., Rioux, J. S., Garlick, R. B., and White, C. W. (2013). Tissue plasminogen activator prevents mortality from sulfur mustard analog-induced airway obstruction. Am. J. Respir. Cell Mol. Biol. 48, 439–447). It is not known if exposure to neat SM vapor, the primary agent used in chemical warfare, will also cause death due to airway casts, and if tPA could be used to improve outcome. Methods: Adult rats were exposed to SM, and when oxygen saturation reached less than 85% (median: 6.5 h), intratracheal tPA or placebo was given under isoflurane anesthesia every 4 h for 48 h. Oxygen saturation, clinical distress, and arterial blood gases were assessed. Microdissection was done to assess airway obstruction by casts. Results: Intratracheal tPA treatment eliminated mortality (0% at 48 h) and greatly improved morbidity after lethal SM inhalation (100% death in controls). tPA normalized SM-associated hypoxemia, hypercarbia, and lactic acidosis, and improved respiratory distress. Moreover, tPA treatment resulted in greatly diminished airway casts, preventing respiratory failure from airway obstruction. Conclusions: tPA given via airway more than 6 h after exposure prevented death from lethal SM inhalation, and normalized oxygenation and ventilation defects, thereby rescuing from respiratory distress and failure. Intra-airway tPA should be considered as a life

  13. Small airway remodeling in acute respiratory distress syndrome: a study in autopsy lung tissue

    PubMed Central

    2011-01-01

    Introduction Airway dysfunction in patients with the Acute Respiratory Distress Syndrome (ARDS) is evidenced by expiratory flow limitation and dynamic hyperinflation. These functional alterations have been attributed to closure/obstruction of small airways. Airway morphological changes have been reported in experimental models of acute lung injury, characterized by epithelial necrosis and denudation in distal airways. To date, however, no study has focused on the morphological airway changes in lungs from human subjects with ARDS. The aim of this study is to evaluate structural and inflammatory changes in distal airways in ARDS patients. Methods We retrospectively studied autopsy lung tissue from subjects who died with ARDS and from control subjects who died of non pulmonary causes. Using image analysis, we quantified the extension of epithelial changes (normal, abnormal and denudated epithelium expressed as percentages of the total epithelium length), bronchiolar inflammation, airway wall thickness, and extracellular matrix (ECM) protein content in distal airways. The Student's t-test or the Mann-Whitney test was used to compare data between the ARDS and control groups. Bonferroni adjustments were used for multiple tests. The association between morphological and clinical data was analyzed by Pearson rank test. Results Thirty-one ARDS patients (A: PaO2/FiO2 ≤200, 45 ± 14 years, 16 males) and 11 controls (C: 52 ± 16 years, 7 males) were included in the study. ARDS airways showed a shorter extension of normal epithelium (A:32.9 ± 27.2%, C:76.7 ± 32.7%, P < 0.001), a larger extension of epithelium denudation (A:52.6 ± 35.2%, C:21.8 ± 32.1%, P < 0.01), increased airway inflammation (A:1(3), C:0(1), P = 0.03), higher airway wall thickness (A:138.7 ± 54.3 μm, C:86.4 ± 33.3 μm, P < 0.01), and higher airway content of collagen I, fibronectin, versican and matrix metalloproteinase-9 (MMP-9) compared to controls (P ≤0.03). The extension of normal epithelium

  14. Computational model of soft tissues in the human upper airway.

    PubMed

    Pelteret, J-P V; Reddy, B D

    2012-01-01

    This paper presents a three-dimensional finite element model of the tongue and surrounding soft tissues with potential application to the study of sleep apnoea and of linguistics and speech therapy. The anatomical data was obtained from the Visible Human Project, and the underlying histological data was also extracted and incorporated into the model. Hyperelastic constitutive models were used to describe the material behaviour, and material incompressibility was accounted for. An active Hill three-element muscle model was used to represent the muscular tissue of the tongue. The neural stimulus for each muscle group was determined through the use of a genetic algorithm-based neural control model. The fundamental behaviour of the tongue under gravitational and breathing-induced loading is investigated. It is demonstrated that, when a time-dependent loading is applied to the tongue, the neural model is able to control the position of the tongue and produce a physiologically realistic response for the genioglossus. PMID:25830209

  15. 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

  16. Endovascular Placement of an Extraluminal Femoropopliteal Bypass Graft in Human Cadavers

    SciTech Connect

    Maynar, Manuel; Llorens, Rafael; Lopez-Sanchez, Carmen; Garcia-Martinez, Virginio; Qian Zhong; Lopera, Jorge; Castaneda, Wilfrido R.

    2005-04-15

    Purpose. A method to create an extraluminal femoropopliteal bypass graft using endovascular techniques was evaluated in situ on cadaver extremities in an attempt to develop a minimally invasive alternative technique for the management of infrainguinal occlusive arterial disease. Methods. The endovascular placement of an extraluminal femoropopliteal bypass graft was undertaken in 5 cadaver legs. Following percutaneous access to the popliteal artery (PA) or common femoral artery (CFA), a Rosch-Uchida needle was used to perforate the vascular wall, followed by the creation of an extraluminal tract using a looped wire and catheter. Once the desired level was reached the needle was again used to perforate the vascular wall of the proximal superficial femoral artery (SFA) or PA depending on the access used. Self-expanding expanded polytetrafluoroethylene (ePTFE) stent-grafts were then deployed to establish the extraluminal femoropopliteal bypass connecting the two arterial puncture sites. Following dilatation of the stent-graft, angiography was performed to assess the endoprostheses and to look for contrast leaks. Results. Technical success was achieved in all 5 legs. Procedure time varied from 15 to 30 min. The angiographic studies performed immediately after completion of the bypass procedure showed patency of the grafts with no evidence of kinking or leakage in any of the cases. Conclusion. This study has proved that the endovascular placement of an extraluminal femoropopliteal bypass graft in human cadaver legs using endovascular techniques under fluoroscopic control is technically feasible.

  17. 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

  18. Current Perspectives in Mesenchymal Stromal Cell Therapies for Airway Tissue Defects

    PubMed Central

    Petrella, Francesco; Rizzo, Stefania; Borri, Alessandro; Casiraghi, Monica; Spaggiari, Lorenzo

    2015-01-01

    Lung cancer is the leading cause of cancer death and respiratory diseases are the third cause of death in industrialized countries; for this reason the airways and cardiopulmonary system have been the focus of extensive investigation, in particular of the new emerging branch of regenerative medicine. Mesenchymal stromal cells (MSCs) are a population of undifferentiated multipotent adult cells that naturally reside within the human body, which can differentiate into osteogenic, chondrogenic, and adipogenic lineages when cultured in specific inducing media. MSCs have the ability to migrate and engraft at sites of inflammation and injury in response to cytokines, chemokines, and growth factors at a wound site and they can exert local reparative effects through transdifferentiation and differentiation into specific cell types or via the paracrine secretion of soluble factors with anti-inflammatory and wound-healing activities. Experimental and clinical evidence exists regarding MSCs efficacy in airway defects restoration; although clinical MSCs use, in the daily practice, is not yet completely reached for airway diseases, we can argue that MSCs do not represent any more merely an experimental approach to airway tissue defects restoration but they can be considered as a “salvage” therapeutic tool in very selected patients and diseases. PMID:26167186

  19. Unilateral arytenoid lateralisation and extraluminal polypropylene ring prostheses for correction of tracheal collapse in the dog.

    PubMed

    White, R N

    1995-04-01

    The surgical repair of tracheal collapse in 25 dogs is described. The initial presenting signs included coughing, dyspnoea, gagging, retching, exercise intolerance, cyanosis and collapse. Diagnosis was based upon the clinical signs, plain radiography and tracheal endoscopy. The collapse was corrected by the application of a number of extraluminal polypropylene prosthetic rings applied to the affected trachea. Additionally, a left arytenoid lateralisation was also performed. The perioperative complication rate was approximately 4 per cent, while the success rate was 75 per cent. The technique reduces the likelihood of catastrophic postoperative complications associated with iatrogenic laryngeal paralysis which is a possible complication of placement of extraluminal tracheal support devices. PMID:7603056

  20. Increased Epicardial Adipose Tissue Is Associated with the Airway Dominant Phenotype of Chronic Obstructive Pulmonary Disease

    PubMed Central

    Higami, Yuichi; Ogawa, Emiko; Ryujin, Yasushi; Goto, Kenichi; Seto, Ruriko; Wada, Hiroshi; Tho, Nguyen Van; Lan, Le Thi Tuyet; Paré, Peter D.; Nakano, Yasutaka

    2016-01-01

    Background Epicardial adipose tissue (EAT) has been shown to be a non-invasive marker that predicts the progression of cardiovascular disease (CVD). It has been reported that the EAT volume is increased in patients with chronic obstructive pulmonary disease (COPD). However, little is known about which phenotypes of COPD are associated with increased EAT. Methods One hundred and eighty smokers who were referred to the clinic were consecutively enrolled. A chest CT was used for the quantification of the emphysematous lesions, airway lesions, and EAT. These lesions were assessed as the percentage of low attenuation volume (LAV%), the square root of airway wall area of a hypothetical airway with an internal perimeter of 10 mm (√Aaw at Pi10) and the EAT area, respectively. The same measurements were made on 225 Vietnamese COPD patients to replicate the results. Results Twenty-six of the referred patients did not have COPD, while 105 were diagnosed as having COPD based on a FEV1/FVC<0.70. The EAT area was significantly associated with age, BMI, FEV1 (%predicted), FEV1/FVC, self-reported hypertension, self-reported CVD, statin use, LAV%, and √Aaw at Pi10 in COPD patients. The multiple regression analyses showed that only BMI, self-reported CVD and √Aaw at Pi10 were independently associated with the EAT area (R2 = 0.51, p<0.0001). These results were replicated in the Vietnamese population. Conclusions The EAT area is independently associated with airway wall thickness. Because EAT is also an independent predictor of CVD risk, these data suggest a mechanistic link between the airway predominant form of COPD and CVD. PMID:26866482

  1. Tissue Plasminogen Activator Prevents Mortality from Sulfur Mustard Analog–Induced Airway Obstruction

    PubMed Central

    Hendry-Hofer, Tara B.; Loader, Joan E.; Rioux, Jacqueline S.; Garlick, Rhonda B.; White, Carl W.

    2013-01-01

    Sulfur mustard (SM) inhalation causes the rare but life-threatening disorder of plastic bronchitis, characterized by bronchial cast formation, resulting in severe airway obstruction that can lead to respiratory failure and death. Mortality in those requiring intubation is greater than 80%. To date, no antidote exists for SM toxicity. In addition, therapies for plastic bronchitis are solely anecdotal, due to lack of systematic research available to assess drug efficacy in improving mortality and/or morbidity. Adult rats exposed to SM analog were treated with intratracheal tissue plasminogen activator (tPA) (0.15–0.7 mg/kg, 5.5 and 6.5 h), compared with controls (no treatment, isoflurane, and placebo). Respiratory distress and pulse oximetry were assessed (for 12 or 48 h), and arterial blood gases were obtained at study termination (12 h). Microdissection of fixed lungs was done to assess airway obstruction by casts. Optimal intratracheal tPA treatment (0.7 mg/kg) completely eliminated mortality (0% at 48 h), and greatly improved morbidity in this nearly uniformly fatal disease model (90–100% mortality at 48 h). tPA normalized plastic bronchitis–associated hypoxemia, hypercarbia, and lactic acidosis, and improved respiratory distress (i.e., clinical scores) while decreasing airway fibrin casts. Intratracheal tPA diminished airway-obstructive fibrin–containing casts while improving clinical respiratory distress, pulmonary gas exchange, tissue oxygenation, and oxygen utilization in our model of severe chemically induced plastic bronchitis. Most importantly, mortality, which was associated with hypoxemia and clinical respiratory distress, was eliminated. PMID:23258228

  2. Lung-resident tissue macrophages generate Foxp3+ regulatory T cells and promote airway tolerance.

    PubMed

    Soroosh, Pejman; Doherty, Taylor A; Duan, Wei; Mehta, Amit Kumar; Choi, Heonsik; Adams, Yan Fei; Mikulski, Zbigniew; Khorram, Naseem; Rosenthal, Peter; Broide, David H; Croft, Michael

    2013-04-01

    Airway tolerance is the usual outcome of inhalation of harmless antigens. Although T cell deletion and anergy are likely components of tolerogenic mechanisms in the lung, increasing evidence indicates that antigen-specific regulatory T cells (inducible Treg cells [iTreg cells]) that express Foxp3 are also critical. Several lung antigen-presenting cells have been suggested to contribute to tolerance, including alveolar macrophages (MØs), classical dendritic cells (DCs), and plasmacytoid DCs, but whether these possess the attributes required to directly promote the development of Foxp3(+) iTreg cells is unclear. Here, we show that lung-resident tissue MØs coexpress TGF-β and retinal dehydrogenases (RALDH1 and RALDH 2) under steady-state conditions and that their sampling of harmless airborne antigen and presentation to antigen-specific CD4 T cells resulted in the generation of Foxp3(+) Treg cells. Treg cell induction in this model depended on both TGF-β and retinoic acid. Transfer of the antigen-pulsed tissue MØs into the airways correspondingly prevented the development of asthmatic lung inflammation upon subsequent challenge with antigen. Moreover, exposure of lung tissue MØs to allergens suppressed their ability to generate iTreg cells coincident with blocking airway tolerance. Suppression of Treg cell generation required proteases and TLR-mediated signals. Therefore, lung-resident tissue MØs have regulatory functions, and strategies to target these cells might hold promise for prevention or treatment of allergic asthma. PMID:23547101

  3. 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

  4. High-Dose-Rate Endobronchial Brachytherapy for Recurrent Airway Obstruction From Hyperplastic Granulation Tissue

    SciTech Connect

    Tendulkar, Rahul D. Fleming, Peter A.; Reddy, Chandana A.; Gildea, Thomas R.; Machuzak, Michael; Mehta, Atul C.

    2008-03-01

    Purpose: Benign endobronchial granulation tissue causes airway obstruction in up to 20% of patients after lung transplantation or stent placement. High-dose-rate endobronchial brachytherapy (HDR-EB) has been successful in some cases refractory to standard bronchoscopic interventions. Methods and Materials: Between September 2004 and May 2005, 8 patients with refractory benign airway obstruction were treated with HDR-EB, using one to two fractions of Ir-192 prescribed to 7.1 Gy at a radius of 1 cm. Charts were retrospectively reviewed to evaluate subjective clinical response, forced expiratory volume in 1 second (FEV{sub 1}), and frequency of therapeutic bronchoscopies over 6-month periods before and after HDR-EB. Results: The median follow-up was 14.6 months, and median survival was 10.5 months. The mean number of bronchoscopic interventions improved from 3.1 procedures in the 6-month pretreatment period to 1.8 after HDR-EB. Mean FEV{sub 1} improved from 36% predicted to 46% predicted. Six patients had a good-to-excellent subjective early response, but only one maintained this response beyond 6 months, and this was the only patient treated with HDR-EB within 24 h from the most recent bronchoscopic intervention. Five patients have expired from causes related to their chronic pulmonary disease, including one from hemoptysis resulting from a bronchoarterial fistula. Conclusion: High-dose-rate-EB may be an effective treatment for select patients with refractory hyperplastic granulation tissue causing recurrent airway stenosis. Performing HDR-EB within 24-48 h after excision of obstructive granulation tissue could further improve outcomes. Careful patient selection is important to maximize therapeutic benefit and minimize toxicity. The optimal patient population, dose, and timing of HDR-EB should be investigated prospectively.

  5. Tissue-engineered endothelial and epithelial implants differentially and synergistically regulate airway repair.

    PubMed

    Zani, Brett G; Kojima, Koji; Vacanti, Charles A; Edelman, Elazer R

    2008-05-13

    The trilaminate vascular architecture provides biochemical regulation and mechanical integrity. Yet regulatory control can be regained after injury without recapitulating tertiary structure. Tissue-engineered (TE) endothelium controls repair even when placed in the perivascular space of injured vessels. It remains unclear from vascular repair studies whether endothelial implants recapitulate the vascular epithelial lining or expose injured tissues to endothelial cells (ECs) with unique healing potential because ECs line the vascular epithelium and the vasa vasorum. We examined this issue in a nonvascular tubular system, asking whether airway repair is controlled by bronchial epithelial cells (EPs) or by ECs of the perfusing bronchial vasculature. Localized bronchial denuding injury damaged epithelium, narrowed bronchial lumen, and led to mesenchymal cell hyperplasia, hypervascularity, and inflammatory cell infiltration. Peribronchial TE constructs embedded with EPs or ECs limited airway injury, although optimum repair was obtained when both cells were present in TE matrices. EC and EP expression of PGE(2), TGFbeta1, TGFbeta2, GM-CSF, IL-8, MCP-1, and soluble VCAM-1 and ICAM-1 was altered by matrix embedding, but expression was altered most significantly when both cells were present simultaneously. EPs may provide for functional control of organ injury and fibrous response, and ECs may provide for preservation of tissue perfusion and the epithelium in particular. Together the two cells optimize functional restoration and healing, suggesting that multiple cells of a tissue contribute to the differentiated biochemical function and repair of a tissue, but need not assume a fixed, ordered architectural relationship, as in intact tissues, to achieve these effects. PMID:18458330

  6. Airway and tissue impedances of canine lungs after step volume changes.

    PubMed

    Bates, J H; Donoso, F A; Peslin, R

    1993-10-01

    We investigated the changes in pulmonary mechanics in five anesthetized paralyzed tracheostomized open-chest dogs after step changes in lung volume. We applied small-amplitude (10-ml) volume oscillations at 6 Hz at the tracheal opening for 50-s periods, during which we applied a step volume change of 250, 500, or 750 ml to the lungs. Alveolar capsule measurements of alveolar pressure allowed us to calculate cycle-by-cycle values for airway resistance (Raw) and reactance (Xaw) and lung tissue resistance (Rti) and reactance (Xti). Before the step changes in lung volume, when transpulmonary pressure (Ptp) had a mean value of 0.65 kPa, Raw was markedly greater than Rti. The situation was reversed after the step changes, however, when Raw decreased and Rti increased. Both Raw and Xaw showed negative dependences on Ptp and hence on airway caliber, as expected, and also decreased transiently after the step volume changes, almost certainly due to a vagally mediated bronchodilation reflex. Both Rti and Xti showed clear linear dependences on Ptp and were themselves tightly coupled. Furthermore, our estimate of bulk modulus for lung tissue at 6 Hz is comparable to its previously reported values at much lower oscillation frequencies. PMID:8282590

  7. Airway mechanics and lung tissue viscoelasticity: effects of altered blood hematocrit in the pulmonary circulation.

    PubMed

    Peták, Ferenc; Fodor, Gergely H; Babik, Barna; Habre, Walid

    2016-07-01

    The contribution of the hematocrit (Hct) of the blood in the pulmonary vasculature to the overall lung mechanics has not been characterized. We therefore set out to establish how changes of the Hct level in the pulmonary circulation affect the airway and lung tissue viscoelastic properties. The Hct level of the blood in an isolated perfused rat lung model was randomly altered. Intermediate (26.5%), followed by low (6.6%) or normal (43.7%), Hct was set in two consecutive sequences. The pulmonary capillary pressure was maintained constant throughout the experiment, and the pulmonary hemodynamic parameters were monitored continuously. The airway resistance (Raw), the viscous (G) and elastic (H) parameters, and the hysteresivity (η = G/H) of the lung tissues were obtained from measurements of forced oscillatory input impedance data. Raw was not affected by the alterations of the Hct levels. As concerns the lung tissues, the decrease of Hct to intermediate or low levels resulted in close to proportional decreases in the viscoelastic parameters G [16.5 ± 7.7% (SD), 12.1 ± 9.5%, P < 0.005] and H (13.2 ± 8.6%, 10.8 ± 4.7%, P < 0.001). No significant changes in η were detected in a wide range of Hct, which indicates that coupled processes cause alterations in the resistive and elastic properties of the lungs following Hct changes in the pulmonary circulation. The diminishment of the viscous and elastic parameters of the pulmonary parenchyma following a reduction of blood Hct demonstrates the significant contribution of the red blood cells to the overall lung viscoelasticity. PMID:27283919

  8. Endoscopic Ultrasound-Guided Drainage without Fluoroscopic Guidance for Extraluminal Complicated Cysts

    PubMed Central

    Nam, Hyeong Seok; Kim, Hyung Wook; Kang, Dae Hwan; Choi, Cheol Woong; Park, Su Bum; Kim, Su Jin; Ryu, Dae Gon; Jeon, Joon Ho

    2016-01-01

    Background. Endoscopic ultrasound- (EUS-) guided drainage is generally performed under fluoroscopic guidance. However, improvements in endoscopic and EUS techniques and experience have led to questions regarding the usefulness of fluoroscopy. This study aimed to retrospectively evaluate the safety and efficacy of EUS-guided drainage of extraluminal complicated cysts without fluoroscopic guidance. Methods. Patients who had undergone nonfluoroscopic EUS-guided drainage of extraluminal complicated cysts were enrolled. Drainage was performed via a transgastric, transduodenal, or transrectal approach. Single or double 7 Fr double pigtail stents were inserted. Results. Seventeen procedures were performed in 15 patients in peripancreatic fluid collections (n = 13) and pelvic abscesses (n = 4). The median lesion size was 7.1 cm (range: 2.8–13.0 cm), and the mean time spent per procedure was 26.2 ± 9.8 minutes (range: 16–50 minutes). Endoscopic drainage was successful in 16 of 17 (94.1%) procedures. There were no complications. All patients experienced symptomatic improvement and revealed partial to complete resolution according to follow-up computed tomography findings. Two patients developed recurrent cysts that were drained during repeat procedures, with eventual complete resolution. Conclusion. EUS-guided drainage without fluoroscopic guidance is a technically feasible, safe, and effective procedure for the treatment of extraluminal complicated cysts. PMID:27313606

  9. 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

  10. 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

  11. [Giant gastric neuroendocrine cell carcinoma with extraluminal growth and direct invasion: a case report].

    PubMed

    Okawa, Takaomi; Nogami, Hiromi; Kadota, Eiji

    2015-11-01

    A 68-year-old man presented to our hospital requesting an operation for an anal prolapse. However, because of appetite loss and general malaise, we performed screening gastroscopy that revealed a huge ulcerative lesion in the greater curvature of the middle stomach. Biopsy showed a solid tumor with marked dyskaryosis that was positive for synaptophysin on immunohistochemical staining. Abdominal computed tomography revealed a tumor measuring larger than 20 cm in diameter in the greater curvature of the stomach and two hepatic metastases. A preoperative diagnosis of neuroendocrine cell carcinoma (NEC) was made and the patient underwent surgery. The lesion displayed extraluminal growth and directly infiltrated the ileum and colon. We therefore performed distal gastrectomy with combined resection of the gallbladder, ileum, transverse colon, and sigmoid colon. However, despite transcatheter arterial chemoembolization for the liver metastases, the patient died 1 year 2 months after the initial surgery. Gastric NECs are rare and have poor outcomes, being associated with rapid progression of lymph node and liver metastases. Moreover, they rarely show extraluminal growth or invasion to other organs. We present a report of this case along with a review of the literature. PMID:26537329

  12. Extracellular matrix remodeling by dynamic strain in a three-dimensional tissue-engineered human airway wall model.

    PubMed

    Choe, Melanie M; Sporn, Peter H S; Swartz, Melody A

    2006-09-01

    Airway wall remodeling is a hallmark of asthma, characterized by subepithelial thickening and extracellular matrix (ECM) remodeling. Mechanical stress due to hyperresponsive smooth muscle cells may contribute to this remodeling, but its relevance in a three-dimensional environment (where the ECM plays an important role in modulating stresses felt by cells) is unclear. To characterize the effects of dynamic compression in ECM remodeling in a physiologically relevant three-dimensional environment, a tissue-engineered human airway wall model with differentiated bronchial epithelial cells atop a collagen gel containing lung fibroblasts was used. Lateral compressive strain of 10 or 30% at 1 or 60 cycles per hour was applied using a novel straining device. ECM remodeling was assessed by immunohistochemistry and zymography. Dynamic strain, particularly at the lower magnitude, induced airway wall remodeling, as indicated by increased deposition of types III and IV collagen and increased secretion of matrix metalloproteinase-2 and -9. These changes paralleled increased myofibroblast differentiation and were fibroblast-dependent. Furthermore, the spatial pattern of type III collagen deposition correlated with that of myofibroblasts; both were concentrated near the epithelium and decreased diffusely away from the surface, indicating some epithelial control of the remodeling response. Thus, in a physiologically relevant three-dimensional model of the bronchial wall, dynamic compressive strain induced tissue remodeling that mimics many features of remodeling seen in asthma, in the absence of inflammation and dependent on epithelial-fibroblast signaling. PMID:16601241

  13. 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

  14. Effect of subchronic in vivo exposure to nitrogen dioxide on lung tissue inflammation, airway microvascular leakage, and in vitro bronchial muscle responsiveness in rats.

    PubMed Central

    Chitano, P; Rado, V; Di Stefano, A; Papi, A; Boniotti, A; Zancuoghi, G; Boschetto, P; Romano, M; Salmona, M; Ciaccia, A; Fabbri, L M; Mapp, C E

    1996-01-01

    OBJECTIVES: In a previous study on bronchoalveolar lavage fluid from rats exposed in vivo for seven days to 10 ppm nitrogen dioxide (NO2), it has been shown that there is an influx of macrophages into the airways. The present study investigated the effect of seven day exposure to 10 ppm NO2, on: (a) lung tissue inflammation and morphology; (b) airway microvascular leakage; (c) in vitro contractile response of main bronchi. METHODS: Lung tissue was studied by light microscopy, after fixing the lungs by inflation with 4% formalin at a pressure of 20 cm H2O. Microvascular leakage was measured by extravasation of Evans blue dye in the larynx, trachea, main bronchi, and intrapulmonary airways. Smooth muscle responsiveness was evaluated by concentration-responses curves to acetylcholine (10(-9)-10(-3) M), serotonin (10(-9)-10(-4) M), and voltage-response curves (12-28 V) to electrical field stimulation. RESULTS: Histology showed an increased total inflammation at the level of respiratory bronchioles and alveoli. No influx of inflammatory cells was found in the main bronchi. A loss of cilia in the epithelium of small airways and ectasia of alveolar capillaries was also found. By contrast, no alterations to microvascular permeability or modification of bronchial smooth muscle responsiveness was found. CONCLUSIONS: Subchronic exposure to 10 ppm NO2 causes airway inflammation and structural damage, but does not cause any persistent alteration to microvascular permeability or bronchial smooth muscle responsiveness in rats. Images Figure 1 PMID:8758032

  15. 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

  16. Proteomic Changes of Tissue-Tolerable Plasma Treated Airway Epithelial Cells and Their Relation to Wound Healing

    PubMed Central

    Lendeckel, Derik; Eymann, Christine; Emicke, Philipp; Daeschlein, Georg; Darm, Katrin; O'Neil, Serena; Beule, Achim G.; von Woedtke, Thomas; Völker, Uwe; Weltmann, Klaus-Dieter; Jünger, Michael; Hosemann, Werner; Scharf, Christian

    2015-01-01

    Background. The worldwide increasing number of patients suffering from nonhealing wounds requires the development of new safe strategies for wound repair. Recent studies suggest the possibility of nonthermal (cold) plasma application for the acceleration of wound closure. Methods. An in vitro wound healing model with upper airway S9 epithelial cells was established to determine the macroscopically optimal dosage of tissue-tolerable plasma (TTP) for wound regeneration, while a 2D-difference gel electrophoresis (2D-DIGE) approach was used to quantify the proteomic changes in a hypothesis-free manner and to evaluate the balance of beneficial and adverse effects due to TTP application. Results. Plasma doses from 30 s up to 360 s were tested in relation to wound closure after 24 h, 48 h, 72 h, 96 h, and 120 h, in which lower doses (30, 60, and 120 s) resulted in dose-dependent improved wound healing rate compared to untreated cells. Thereby, the 120 s dose caused significantly the best wound healing properties after 96 and 120 h. The proteome analysis combined with IPA revealed that a lot of affected stress adaptation responses are linked to oxidative stress response emphasizing oxidative stress as a possible key event in the regeneration process of epithelial cells as well as in the adaptation to plasma exposure. Further cellular and molecular functions like proliferation and apoptosis were significantly up- or downregulated by all TTP treatments but mostly by the 120 s dose. Conclusions. For the first time, we were able to show plasma effects on cellular adaptation of upper airway epithelial S9 cells improving wound healing. This is of particular interest for plasma application, for example, in the surgery field of otorhinolaryngology or internal medicine. PMID:26539504

  17. Cost of Stem Cell-Based Tissue-Engineered Airway Transplants in the United Kingdom: Case Series.

    PubMed

    Culme-Seymour, Emily J; Mason, Katrina; Vallejo-Torres, Laura; Carvalho, Carla; Partington, Leanne; Crowley, Claire; Hamilton, Nick J; Toll, Ed C; Butler, Colin R; Elliott, Martin J; Birchall, Martin A; Lowdell, Mark W; Mason, Chris

    2016-02-01

    Stem cell-based tissue-engineered tracheas are at an early stage in their product development cycle. Tens of patients have been treated worldwide in predominantly compassionate use settings, demonstrating significant promise. This potentially life-saving treatment is complex, and the cost and its implications for such treatments are yet to be fully understood. The costs are compounded by varying strategies for graft preparation and transplant, resulting in differing clinical and laboratory costs from different research groups. In this study, we present a detailed breakdown of the clinical and manufacturing costs for three of the United Kingdom (UK) patients treated with such transplants. All three patients were treated under Compassionate Use legislation, within the UK National Health Service (NHS) hospital setting. The total costs for the three UK patients treated ranged from $174,420 to $740,500. All three patients were in a state of poor health at time of treatment and had a number of complexities in addition to the restricted airway. This is the first time a cost analysis has been made for a tissue-engineered organ and provides a benchmark for future studies, as well as comparative data for use in reimbursement considerations. PMID:26559535

  18. Biphasic positive airway pressure minimizes biological impact on lung tissue in mild acute lung injury independent of etiology

    PubMed Central

    2013-01-01

    Introduction Biphasic positive airway pressure (BIVENT) is a partial support mode that employs pressure-controlled, time-cycled ventilation set at two levels of continuous positive airway pressure with unrestricted spontaneous breathing. BIVENT can modulate inspiratory effort by modifying the frequency of controlled breaths. Nevertheless, the optimal amount of inspiratory effort to improve respiratory function while minimizing ventilator-associated lung injury during partial ventilatory assistance has not been determined. Furthermore, it is unclear whether the effects of partial ventilatory support depend on acute lung injury (ALI) etiology. This study aimed to investigate the impact of spontaneous and time-cycled control breaths during BIVENT on the lung and diaphragm in experimental pulmonary (p) and extrapulmonary (exp) ALI. Methods This was a prospective, randomized, controlled experimental study of 60 adult male Wistar rats. Mild ALI was induced by Escherichia coli lipopolysaccharide either intratracheally (ALIp) or intraperitoneally (ALIexp). After 24 hours, animals were anesthetized and further randomized as follows: (1) pressure-controlled ventilation (PCV) with tidal volume (Vt) = 6 ml/kg, respiratory rate = 100 breaths/min, PEEP = 5 cmH2O, and inspiratory-to-expiratory ratio (I:E) = 1:2; or (2) BIVENT with three spontaneous and time-cycled control breath modes (100, 75, and 50 breaths/min). BIVENT was set with two levels of CPAP (Phigh = 10 cmH2O and Plow = 5 cmH2O). Inspiratory time was kept constant (Thigh = 0.3 s). Results BIVENT was associated with reduced markers of inflammation, apoptosis, fibrogenesis, and epithelial and endothelial cell damage in lung tissue in both ALI models when compared to PCV. The inspiratory effort during spontaneous breaths increased during BIVENT-50 in both ALI models. In ALIp, alveolar collapse was higher in BIVENT-100 than PCV, but decreased during BIVENT-50, and diaphragmatic injury was lower during BIVENT-50 compared

  19. Kinetics of naphthalene metabolism in target and non-target tissues of rodents and in nasal and airway microsomes from the Rhesus monkey

    SciTech Connect

    Buckpitt, Alan; Morin, Dexter; Murphy, Shannon; Edwards, Patricia; Van Winkle, Laura

    2013-07-15

    Naphthalene produces species and cell selective injury to respiratory tract epithelial cells of rodents. In these studies we determined the apparent K{sub m}, V{sub max}, and catalytic efficiency (V{sub max}/K{sub m}) for naphthalene metabolism in microsomal preparations from subcompartments of the respiratory tract of rodents and non-human primates. In tissues with high substrate turnover, major metabolites were derived directly from naphthalene oxide with smaller amounts from conjugates of diol epoxide, diepoxide, and 1,2- and 1,4-naphthoquinones. In some tissues, different enzymes with dissimilar K{sub m} and V{sub max} appeared to metabolize naphthalene. The rank order of V{sub max} (rat olfactory epithelium > mouse olfactory epithelium > murine airways ≫ rat airways) correlated well with tissue susceptibility to naphthalene. The V{sub max} in monkey alveolar subcompartment was 2% that in rat nasal olfactory epithelium. Rates of metabolism in nasal compartments of the monkey were low. The catalytic efficiencies of microsomes from known susceptible tissues/subcompartments are 10 and 250 fold higher than in rat airway and monkey alveolar subcompartments, respectively. Although the strong correlations between catalytic efficiencies and tissue susceptibility suggest that non-human primate tissues are unlikely to generate metabolites at a rate sufficient to produce cellular injury, other studies showing high levels of formation of protein adducts support the need for additional studies. - Highlights: • Naphthalene is metabolized with high catalytic efficiency in susceptible tissue. • Naphthalene is metabolized at low catalytic efficiency in non-susceptible tissue. • Respiratory tissues of the non human primate metabolize naphthalene slowly.

  20. 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.

  1. Identification of Meningococcal Genes Necessary for Colonization of Human Upper Airway Tissue

    PubMed Central

    Exley, Rachel M.; Sim, Richard; Goodwin, Linda; Winterbotham, Megan; Schneider, Muriel C.; Read, Robert C.; Tang, Christoph M.

    2009-01-01

    Neisseria meningitidis is an exclusively human pathogen that has evolved primarily to colonize the nasopharynx rather than to cause systemic disease. Colonization is the most frequent outcome following meningococcal infection and a prerequisite for invasive disease. The mechanism of colonization involves attachment of the organism to epithelial cells via bacterial type IV pili (Tfp), but subsequent events during colonization remain largely unknown. We analyzed 576 N. meningitidis mutants for their capacity to colonize human nasopharyngeal tissue in an organ culture model to identify bacterial genes required for colonization. Eight colonization-defective mutants were isolated. Two mutants were unable to express Tfp and were defective for adhesion to epithelial cells, which is likely to be the basis of their attenuation in nasopharyngeal tissue. Three other mutants are predicted to have lost previously uncharacterized surface molecules, while the remaining mutants have transposon insertions in genes of unknown function. We have identified novel meningococcal colonization factors, and this should provide insights into the survival of this important pathogen in its natural habitat. PMID:18936183

  2. Pegylation of Antimicrobial Peptides Maintains the Active Peptide Conformation, Model Membrane Interactions, and Antimicrobial Activity while Improving Lung Tissue Biocompatibility following Airway Delivery

    PubMed Central

    Morris, Christopher J.; Beck, Konrad; Fox, Marc A.; Ulaeto, David; Clark, Graeme C.

    2012-01-01

    Antimicrobial peptides (AMPs) have therapeutic potential, particularly for localized infections such as those of the lung. Here we show that airway administration of a pegylated AMP minimizes lung tissue toxicity while nevertheless maintaining antimicrobial activity. CaLL, a potent synthetic AMP (KWKLFKKIFKRIVQRIKDFLR) comprising fragments of LL-37 and cecropin A peptides, was N-terminally pegylated (PEG-CaLL). PEG-CaLL derivatives retained significant antimicrobial activity (50% inhibitory concentrations [IC50s] 2- to 3-fold higher than those of CaLL) against bacterial lung pathogens even in the presence of lung lining fluid. Circular dichroism and fluorescence spectroscopy confirmed that conformational changes associated with the binding of CaLL to model microbial membranes were not disrupted by pegylation. Pegylation of CaLL reduced AMP-elicited cell toxicity as measured using in vitro lung epithelial primary cell cultures. Further, in a fully intact ex vivo isolated perfused rat lung (IPRL) model, airway-administered PEG-CaLL did not result in disruption of the pulmonary epithelial barrier, whereas CaLL caused an immediate loss of membrane integrity leading to pulmonary edema. All AMPs (CaLL, PEG-CaLL, LL-37, cecropin A) delivered to the lung by airway administration showed limited (<3%) pulmonary absorption in the IPRL with extensive AMP accumulation in lung tissue itself, a characteristic anticipated to be beneficial for the treatment of pulmonary infections. We conclude that pegylation may present a means of improving the lung biocompatibility of AMPs designed for the treatment of pulmonary infections. PMID:22430978

  3. 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

  4. Unusual clinical case: extraluminal manifestation of a tapeworm from the eviscerated midline incision in a post-surgery patient.

    PubMed

    Dural, Ahmet Cem; Celik, Muhammet Ferhat; Temizgonul, Baha; Unsal, Mustafa Gokhan; Akarsu, Cevher; Gonenc, Murat; Kalayci, Mustafa Uygar; Alis, Halil

    2015-04-01

    Taenia saginata infestation is one of the most common cestode infestations in humans, that may cause gastrointestinal tract related complications as a result of obstruction, perforation or anastomotic leakage. A 55-year-old male patient who was receiving palliative chemotherapy for stage IV gastric cancer was admitted to the emergency department for abdominal pain. A hollow viscus organ perforation was diagnosed and an emergency surgery was performed. On postoperative day 5, the patient's midline incision eviscerated and a moving taenia emerged, with abundant particulated fluid from the incision line. The patient was admitted for abdominal surgery due to suspected bowel perforation. During the abdominal exploration, a relaxed purse stitch of the feeding tube was observed and no other bowel perforations were seen. The patient underwent two planned surgery for abdominal cavity lavage after the removal of cestode. Unfortunately, the patient died sixteen days after his admission to the intensive care unit. This is the first case describing an extraluminal manifestation of a tapeworm in a midline incision from evisceration without intestinal perforation. PMID:25881535

  5. 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

  6. 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

  7. Comprehensive Airway Management of Patients with Maxillofacial Trauma

    PubMed Central

    Kellman, Robert M.; Losquadro, William D.

    2008-01-01

    Airway management in patients with maxillofacial trauma is complicated by injuries to routes of intubation, and the surgeon is frequently asked to secure the airway. Airway obstruction from hemorrhage, tissue prolapse, or edema may require emergent intervention for which multiple intubation techniques exist. Competing needs for both airway and surgical access create intraoperative conflicts during repair of maxillofacial fractures. Postoperatively, edema and maxillomandibular fixation place the patient at risk for further airway compromise. PMID:22110788

  8. Cigarette smoke activates the proto-oncogene c-src to promote airway inflammation and lung tissue destruction.

    PubMed

    Geraghty, Patrick; Hardigan, Andrew; Foronjy, Robert F

    2014-03-01

    The diagnosis of chronic obstructive pulmonary disease (COPD) confers a 2-fold increased lung cancer risk even after adjusting for cigarette smoking, suggesting that common pathways are operative in both diseases. Although the role of the tyrosine kinase c-Src is established in lung cancer, less is known about its impact in other lung diseases, such as COPD. This study examined whether c-Src activation by cigarette smoke contributes to the pathogenesis of COPD. Cigarette smoke increased c-Src activity in human small airway epithelial (SAE) cells from healthy donors and in the lungs of exposed mice. Similarly, higher c-Src activation was measured in SAE cells from patients with COPD compared with healthy control subjects. In SAE cells, c-Src silencing or chemical inhibition prevented epidermal growth factor (EGF) receptor signaling in response to cigarette smoke but not EGF stimulation. Further studies showed that cigarette smoke acted through protein kinase C α to trigger c-Src to phosphorylate EGF receptor and thereby to induce mitogen-activated protein kinase responses in these cells. To further investigate the role of c-Src, A/J mice were orally administered the specific Src inhibitor AZD-0530 while they were exposed to cigarette smoke for 2 months. AZD-0530 treatment blocked c-Src activation, decreased macrophage influx, and prevented airspace enlargement in the lungs of cigarette smoke-exposed mice. Moreover, inhibiting Src deterred the cigarette smoke-mediated induction of matrix metalloproteinase-9 and -12 in alveolar macrophages and lung expression of cathepsin K, IL-17, TNF-α, MCP-1, and KC, all key factors in the pathogenesis of COPD. These results indicate that activation of the proto-oncogene c-Src by cigarette smoke promotes processes linked to the development of COPD. PMID:24111605

  9. Cigarette Smoke Activates the Proto-Oncogene c-Src to Promote Airway Inflammation and Lung Tissue Destruction

    PubMed Central

    Geraghty, Patrick; Hardigan, Andrew

    2014-01-01

    The diagnosis of chronic obstructive pulmonary disease (COPD) confers a 2-fold increased lung cancer risk even after adjusting for cigarette smoking, suggesting that common pathways are operative in both diseases. Although the role of the tyrosine kinase c-Src is established in lung cancer, less is known about its impact in other lung diseases, such as COPD. This study examined whether c-Src activation by cigarette smoke contributes to the pathogenesis of COPD. Cigarette smoke increased c-Src activity in human small airway epithelial (SAE) cells from healthy donors and in the lungs of exposed mice. Similarly, higher c-Src activation was measured in SAE cells from patients with COPD compared with healthy control subjects. In SAE cells, c-Src silencing or chemical inhibition prevented epidermal growth factor (EGF) receptor signaling in response to cigarette smoke but not EGF stimulation. Further studies showed that cigarette smoke acted through protein kinase C α to trigger c-Src to phosphorylate EGF receptor and thereby to induce mitogen-activated protein kinase responses in these cells. To further investigate the role of c-Src, A/J mice were orally administered the specific Src inhibitor AZD-0530 while they were exposed to cigarette smoke for 2 months. AZD-0530 treatment blocked c-Src activation, decreased macrophage influx, and prevented airspace enlargement in the lungs of cigarette smoke–exposed mice. Moreover, inhibiting Src deterred the cigarette smoke–mediated induction of matrix metalloproteinase-9 and -12 in alveolar macrophages and lung expression of cathepsin K, IL-17, TNF-α, MCP-1, and KC, all key factors in the pathogenesis of COPD. These results indicate that activation of the proto-oncogene c-Src by cigarette smoke promotes processes linked to the development of COPD. PMID:24111605

  10. A Systems Biology Approach Reveals the Dose- and Time-Dependent Effect of Primary Human Airway Epithelium Tissue Culture After Exposure to Cigarette Smoke In Vitro

    PubMed Central

    Mathis, Carole; Gebel, Stephan; Poussin, Carine; Belcastro, Vincenzo; Sewer, Alain; Weisensee, Dirk; Hengstermann, Arnd; Ansari, Sam; Wagner, Sandra; Peitsch, Manuel C; Hoeng, Julia

    2015-01-01

    To establish a relevant in vitro model for systems toxicology-based mechanistic assessment of environmental stressors such as cigarette smoke (CS), we exposed human organotypic bronchial epithelial tissue cultures at the air liquid interface (ALI) to various CS doses. Previously, we compared in vitro gene expression changes with published human airway epithelia in vivo data to assess their similarities. Here, we present a follow-up evaluation of these in vitro transcriptomics data, using complementary computational approaches and an integrated mRNA–microRNA (miRNA) analysis. The main cellular pathways perturbed by CS exposure were related to stress responses (oxidative stress and xenobiotic metabolism), inflammation (inhibition of nuclear factor-κB and the interferon gamma-dependent pathway), and proliferation/differentiation. Within post-exposure periods up to 48 hours, a transient kinetic response was observed at lower CS doses, whereas higher doses resulted in more sustained responses. In conclusion, this systems toxicology approach has potential for product testing according to “21st Century Toxicology”. PMID:25788831

  11. 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

  12. Viscoelastic and dynamic nonlinear properties of airway smooth muscle tissue: roles of mechanical force and the cytoskeleton.

    PubMed

    Ito, Satoru; Majumdar, Arnab; Kume, Hiroaki; Shimokata, Kaoru; Naruse, Keiji; Lutchen, Kenneth R; Stamenovic, Dimitrije; Suki, Béla

    2006-06-01

    The viscoelastic and dynamic nonlinear properties of guinea pig tracheal smooth muscle tissues were investigated by measuring the storage (G') and loss (G") moduli using pseudorandom small-amplitude length oscillations between 0.12 and 3.5 Hz superimposed on static strains of either 10 or 20% of initial length. The G" and G' spectra were interpreted using a linear viscoelastic model incorporating damping (G) and stiffness (H), respectively. Both G and H were elevated following an increase in strain from 10 to 20%. There was no change in harmonic distortion (K(d)), an index of dynamic nonlinearity, between 10 and 20% strains. Application of methacholine at 10% strain significantly increased G and H while it decreased K(d). Cytochalasin D, isoproterenol, and HA-1077, a Rho-kinase inhibitor, significantly decreased both G and H but increased K(d). Following cytochalasin D, G, H, and K(d) were all elevated when mean strain increased from 10 to 20%. There were no changes in hysteresivity, G/H, under any condition. We conclude that not all aspects of the viscoelastic properties of tracheal smooth muscle strips are similar to those previously observed in cultured cells. We attribute these differences to the contribution of the extracellular matrix. Additionally, using a network model, we show that the dynamic nonlinear behavior, which has not been observed in cell culture, is associated with the state of the contractile stress and may derive from active polymerization within the cytoskeleton. PMID:16414980

  13. Peripharyngeal tissue deformation, stress distributions, and hyoid bone movement in response to mandibular advancement.

    PubMed

    Amatoury, Jason; Kairaitis, Kristina; Wheatley, John R; Bilston, Lynne E; Amis, Terence C

    2015-02-01

    Mandibular advancement (MA) increases upper airway (UA) patency and decreases collapsibility. Furthermore, MA displaces the hyoid bone in a cranial-anterior direction, which may contribute to MA-associated UA improvements via redistribution of peripharyngeal tissue stresses (extraluminal tissue pressure, ETP). In the present study, we examined effects of MA on ETP distributions, deformation of the peripharyngeal tissue surface (UA geometry), and hyoid bone position. We studied 13 supine, anesthetized, tracheostomized, spontaneously breathing adult male New Zealand White rabbits. Graded MA was applied from 0 to ∼4.5 mm. ETP was measured at six locations distributed throughout three UA regions: tongue, hyoid, and epiglottis. Axial computed tomography images of the UA (nasal choanae to glottis) were acquired and used to measure lumen geometry (UA length; regional cross-sectional area) and hyoid displacement. MA resulted in nonuniform decreases in ETP (greatest at tongue region), ranging from -0.11 (-0.15 to -0.06) to -0.82 (-1.09 to -0.54) cmH2O/mm MA [linear mixed-effects model slope (95% confidence interval)], across all sites. UA length decreased by -0.5 (-0.8 to -0.2) %/mm accompanied by nonuniform increases in cross-sectional area (greatest at hyoid region) ranging from 7.5 (3.6-11.4) to 18.7 (14.9-22.5) %/mm. The hyoid bone was displaced in a cranial-anterior direction by 0.42 (0.36-0.44) mm/mm MA. In summary, MA results in nonuniform changes in peripharyngeal tissue pressure distributions and lumen geometry. Displacement of the hyoid bone with MA may play a pivotal role in redistributing applied MA loads, thus modifying tissue stress/deformation distributions and determining resultant UA geometry outcomes. PMID:25505028

  14. 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

  15. 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 ...

  16. Airway smooth muscle dynamics: a common pathway of airway obstruction in asthma

    PubMed Central

    An, S.S.; Bai, T.R.; Bates, J.H.T.; Black, J.L.; Brown, R.H.; Brusasco, V.; Chitano, P.; Deng, L.; Dowell, M.; Eidelman, D.H.; Fabry, B.; Fairbank, N.J.; Ford, L.E.; Fredberg, J.J.; Gerthoffer, W.T.; Gilbert, S.H.; Gosens, R.; Gunst, S.J.; Halayko, A.J.; Ingram, R.H.; Irvin, C.G.; James, A.L.; Janssen, L.J.; King, G.G.; Knight, D.A.; Lauzon, A.M.; Lakser, O.J.; Ludwig, M.S.; Lutchen, K.R.; Maksym, G.N.; Martin, J.G.; Mauad, T.; McParland, B.E.; Mijailovich, S.M.; Mitchell, H.W.; Mitchell, R.W.; Mitzner, W.; Murphy, T.M.; Paré, P.D.; Pellegrino, R.; Sanderson, M.J.; Schellenberg, R.R.; Seow, C.Y.; Silveira, P.S.P.; Smith, P.G.; Solway, J.; Stephens, N.L.; Sterk, P.J.; Stewart, A.G.; Tang, D.D.; Tepper, R.S.; Tran, T.; Wang, L.

    2008-01-01

    Excessive airway obstruction is the cause of symptoms and abnormal lung function in asthma. As airway smooth muscle (ASM) is the effecter controlling airway calibre, it is suspected that dysfunction of ASM contributes to the pathophysiology of asthma. However, the precise role of ASM in the series of events leading to asthmatic symptoms is not clear. It is not certain whether, in asthma, there is a change in the intrinsic properties of ASM, a change in the structure and mechanical properties of the noncontractile components of the airway wall, or a change in the interdependence of the airway wall with the surrounding lung parenchyma. All these potential changes could result from acute or chronic airway inflammation and associated tissue repair and remodelling. Anti-inflammatory therapy, however, does not “cure” asthma, and airway hyperresponsiveness can persist in asthmatics, even in the absence of airway inflammation. This is perhaps because the therapy does not directly address a fundamental abnormality of asthma, that of exaggerated airway narrowing due to excessive shortening of ASM. In the present study, a central role for airway smooth muscle in the pathogenesis of airway hyperresponsiveness in asthma is explored. PMID:17470619

  17. 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 ...

  18. Dynamics of airway response in lung microsections: a tool for studying airway-extra cellular matrix interactions.

    PubMed

    Khan, Mohammad Afzal

    2016-01-01

    The biological configuration of extracellular matrix (ECM) plays a key role in how mechanical interactions of the airway with its parenchymal attachments affect the dynamics of airway responses in different pulmonary disorders including asthma, emphysema and chronic bronchitis. It is now recognized that mechanical interactions between airway tissue and ECM play a key regulatory role on airway physiology and kinetics that can lead to the reorganization and remodeling of airway connective tissue. A connective tissue is composed of airway smooth muscle cells (ASM) and the ECM, which includes variety of glycoproteins and therefore the extent of interactions between ECM and ASM affects airway dynamics during exacerbations of major pulmonary disorders. Measurement of the velocity and magnitude of airway closure or opening provide important insights into the functions of the airway contractile apparatus and the interactions with its surrounding connective tissues. This review highlights suitability of lung microsection technique in studying measurements of airway dynamics (narrowing/opening) and associated structural distortions in airway compartments. PMID:27176036

  19. 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

  20. Secondary Reverse Slide Tracheoplasty for Airway Rescue.

    PubMed

    Kopelovich, Jonathan C; Wine, Todd M; Rutter, Michael J; Mitchell, Max B; Prager, Jeremy D

    2016-03-01

    Slide tracheoplasty is used in cases of tracheal stenosis or injury. With expanding indications for its use at tertiary centers, salvage techniques for dehiscence or restenosis after slide tracheoplasty are increasingly relevant. We present a case in which slide tracheoplasty was augmented with an anterior costochondral graft that stenosed again and ultimately failed. We salvaged this airway emergency by performing a secondary reverse slide tracheoplasty. Using this technique, we were able to establish a safe and durable airway using only native airway tissue. PMID:26897214

  1. 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

  2. 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 ...

  3. Effects of lung inflation on airway heterogeneity during histaminergic bronchoconstriction.

    PubMed

    Kaczka, David W; Mitzner, Wayne; Brown, Robert H

    2013-09-01

    Lung inflation has been shown to dilate airways by altering the mechanical equilibrium between opposing airway and parenchymal forces. However, it is not known how heterogeneously such dilation occurs throughout the airway tree. In six anesthetized dogs, we measured the diameters of five to six central airway segments using high-resolution computed tomography, along with respiratory input impedance (Zrs) during generalized aerosol histamine challenge, and local histamine challenge in which the agonist was instilled directly onto the epithelia of the imaged central airways. Airway diameters and Zrs were measured at 12 and 25 cmH2O. The Zrs spectra were fitted with a model that incorporated continuous distributions of airway resistances. Airway heterogeneity was quantified using the coefficient of variation for predefined airway distribution functions. Significant reductions in average central airway diameter were observed at 12 cmH2O for both aerosolized and local challenges, along with significant increases upon inflation to 25 cmH2O. No significant differences were observed for the coefficient of variation of airway diameters under any condition. Significant increases in effective airway resistance as measured by Zrs were observed only for the aerosolized challenge at 12 cmH2O, which was completely reversed upon inflation. We conclude that the lung periphery may be the most dominant contributor to increases in airway resistance and tissue elastance during bronchoconstriction induced by aerosolized histamine. However, isolated constriction of only a few central airway segments may also affect tissue stiffness via interdependence with their surrounding parenchyma. PMID:23813528

  4. 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…

  5. Laser applications in pediatric airway surgery

    NASA Astrophysics Data System (ADS)

    Karamzadeh, Amir M.; Ahuja, Gurpreet S.; Nguyen, John D.; Crumley, Roger

    2003-06-01

    The smaller anatomy and limited access to instrumentation pose a challenge to the pediatric airway surgeon. The enhanced precision and ability to photocoagulate tissue while operating with the laser enhances the surgeon"s ability to successfully treat unique pediatric conditions such subglottic hemangiomas, congenital cysts, respiratory papillomatosis, and laryngeal or tracheal stenosis. Due to its shallow tissue penetration and thermal effect, the carbon dioxide (CO2) laser is generally considered the laser of choice for pediatric airway applications. The potential for increased scarring and damage to underlying tissue caused by the greater penetration depth and thermal effect of the Nd:YAG and KTP lasers preclude their use in this population. In this review, we will describe the specific advantages of using lasers in airway surgery, the current technology and where the current technology is deficient.

  6. Expression of ligands for Siglec-8 and Siglec-9 in human airways and airway cells

    PubMed Central

    Jia, Yi; Yu, Huifeng; Fernandes, Steve M.; Wei, Yadong; Gonzalez-Gil, Anabel; Motari, Mary G.; Vajn, Katarina; Stevens, Whitney W.; Peters, Anju T.; Bochner, Bruce S.; Kern, Robert C.; Schleimer, Robert P.; Schnaar, Ronald L.

    2015-01-01

    Background Balanced activation and inhibition of the immune system ensures pathogen clearance while avoiding hyperinflammation. Siglecs, sialic acid binding proteins found on subsets of immune cells, often inhibit inflammation: Siglec-8 on eosinophils and Siglec-9 on neutrophils engage sialoglycan ligands on airways to diminish ongoing inflammation. The identities of human siglec ligands and their expression during inflammation are largely unknown. Objective The histological distribution, expression and molecular characteristics of siglec ligands were explored in healthy and inflamed human upper airways and in a cellular model of airway inflammation. Methods Normal and chronically inflamed upper airway tissues were stained for siglec ligands. The ligands were extracted from normal and inflamed tissues and from human Calu-3 cells for quantitative analysis by siglec blotting and isolation by siglec capture. Results Siglec-8 ligands were expressed on a subpopulation of submucosal gland cells of human inferior turbinate, whereas Siglec-9 ligands were expressed more broadly (submucosal glands, epithelium, connective tissue); both were significantly upregulated in chronic rhinosinusitis patients. Human airway (Calu-3) cells expressed Siglec-9 ligands on mucin 5B under inflammatory control via the NF-κB pathway, and mucin 5B carried sialoglycan ligands of Siglec-9 on human upper airway tissue. Conclusion Inflammation results in upregulation of immune inhibitory Siglec-8 and Siglec-9 sialoglycan ligands on human airways. Siglec-9 ligands were upregulated via the NF-κB pathway resulting in their enhanced expression on mucin 5B. Siglec sialoglycan ligand expression in inflamed cells and tissues may contribute to the control of airway inflammation. PMID:25747723

  7. 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

  8. 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

  9. Airway wall eosinophilia is not a feature of equine heaves.

    PubMed

    Dubuc, J; Lavoie, J-P

    2014-11-01

    The objective of this study was to determine whether eosinophils infiltrate the airway wall of horses with heaves. Eosinophils were evaluated using paraffin embedded lung tissues from six heaves-affected horses in crisis and six aged-matched controls. Slides were stained using Luna's method and eosinophils enumerated using histomorphometric techniques. Total eosinophil counts (expressed per mm(2) of basement membrane) were significantly higher in the airways of controls horses than in horses with heaves. Intraluminal, intraepithelial, and airway smooth muscle eosinophils counts were also increased in control horses. The results suggest that eosinophils do not contribute to the persistent airway obstruction in heaves. PMID:25239297

  10. Acid-sensing by airway afferent nerves

    PubMed Central

    Lee, Lu-Yuan; Gu, Qihai; Xu, Fadi; Hong, Ju-Lun

    2013-01-01

    Inhalation of acid aerosol or aspiration of acid solution evokes a stimulatory effect on airway C-fiber and Aδ afferents, which in turn causes airway irritation and triggers an array of defense reflex responses (e.g., cough, reflex bronchoconstriction, etc.). Tissue acidosis can also occur locally in the respiratory tract as a result of ischemia or inflammation, such as in the airways of asthmatic patients during exacerbation. The action of proton on the airway sensory neurons is generated by activation of two different current species: a transient (rapidly activating and inactivating) current mediated through the acid-sensing ion channels, and a slowly activating and sustained current mediated through the transient receptor potential vanilloid type 1 (TRPV1) receptor. In view of the recent findings that the expression and/or sensitivity of TRPV1 are up-regulated in the airway sensory nerves during chronic inflammatory reaction, the proton-evoked irritant effects on these nerves may play an important part in the manifestation of various symptoms associated with airway inflammatory diseases. PMID:23524016

  11. Interleukin-20 promotes airway remodeling in asthma.

    PubMed

    Gong, Wenbin; Wang, Xin; Zhang, Yuguo; Hao, Junqing; Xing, Chunyan; Chu, Qi; Wang, Guicheng; Zhao, Jiping; Wang, Junfei; Dong, Qian; Liu, Tian; Zhang, Yuanyuan; Dong, Liang

    2014-12-01

    Previous studies have demonstrated that interleukin-20 (IL-20) is a pro-inflammatory cytokine, and it has been implicated in psoriasis, lupus nephritis, rheumatoid arthritis, atherosclerosis, and ulcerative colitis. Little is known about the effects of IL-20 in airway remodeling in asthma. The aim of our study was to demonstrate the function of IL-20 in airway remodeling in asthma. To identify the expression of IL-20 and its receptor, IL-20R1/IL-20R2, in the airway epithelium in bronchial tissues, bronchial biopsy specimens were collected from patients and mice with asthma and healthy subjects and stained with specific antibodies. To characterize the effects of IL-20 in asthmatic airway remodeling, we silenced and stimulated IL-20 in cell lines isolated from mice by shRNA and recombinant protein approaches, respectively, and detected the expression of α-SMA and FN-1 by Western blot analysis. First, overexpression of IL-20 and its receptor, IL-20R1/IL-20R2, was detected in the airway epithelium collected from patients and mice with asthma. Second, IL-20 increased the expression of fibronectin-1 and α-SMA, and silencing of IL-20 in mouse lung epithelial (MLE)-12 cells decreased the expression of fibronectin-1 and α-SMA. IL-20 may be a critical cytokine in airway remodeling in asthma. This study indicates that targeting IL-20 and/or its receptors may be a new therapeutic strategy for asthma. PMID:25028099

  12. 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

  13. Calcinosis cutis: A rare cause for difficult airway

    PubMed Central

    Nanjundaswamy, Nethra H.

    2015-01-01

    Calcinosis cutis is a rare clinical condition wherein calcium is deposited in the layers of the skin. Various types of calcinosis cutis have been described based on histology and location. Airway may be involved only if calcinosis cutis is associated with overlapping syndrome of connective tissue disorders and muscular dystrophy. I report a rare case of dystrophic calcinosis cutis without any connective tissue disorders with the unanticipated difficult airway. A young lady with dystrophic calcinosis cutis of the gluteal region was posted for surgical excision and flap cover procedure under general anesthesia. Unanticipated difficult airway situation arised and was effectively managed. Patient had an uneventful recovery. PMID:26712983

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  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. 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).

  1. Acoustic simulation of a patient's obstructed airway.

    PubMed

    van der Velden, W C P; van Zuijlen, A H; de Jong, A T; Lynch, C T; Hoeve, L J; Bijl, H

    2016-01-01

    This research focuses on the numerical simulation of stridor; a high pitched, abnormal noise, resulting from turbulent airflow and vibrating tissue through a partially obstructed airway. Characteristics of stridor noise are used by medical doctors as indication for location and size of the obstruction. The relation between type of stridor and the various diseases associated with airway obstruction is unclear; therefore, simply listening to stridor is an unreliable diagnostic tool. The overall aim of the study is to better understand the relationship between characteristics of stridor noise and localization and size of the obstruction. Acoustic analysis of stridor may then in future simplify the diagnostic process, and reduce the need for more invasive procedures such as laryngoscopy under general anesthesia. In this paper, the feasibility of a coupled flow, acoustic and structural model is investigated to predict the noise generated by the obstruction as well as the propagation of the noise through the airways, taking into account a one-way coupled fluid, structure, and acoustic interaction components. The flow and acoustic solver are validated on a diaphragm and a simplified airway model. A realistic airway model of a patient suffering from a subglottic stenosis, derived from a real computed tomography scan, is further analyzed. Near the mouth, the broadband noise levels at higher frequencies increased with approximately 15-20 dB comparing the stridorous model with the healthy model, indicating stridorous sound. PMID:25567545

  2. 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.

  3. Airway Surgery in Tracheostomised Patients with Wegener Granulomatosis Leading to Subglottic Stenosis.

    PubMed

    Altun, Demet; Sivrikoz, Nükhet; Çamcı, Emre

    2015-10-01

    Wegener granulomatosis (WG) is a multisystemic disorder characterised by granulomatous inflammation of the respiratory system. The growing of proliferative tissue towards the larynx and trachea may cause airway obstruction on account of subglottic stenosis. In this situation, the surgical goal is to eliminate the airway obstruction by providing natural airway anatomy. While mild lesions do not require surgical intervention, in fixed lesions, surgical intervention is required, such as tracheostomy, laser resection and dilatation. In tracheostomised patients, granuloma formation surrounding the tracheostomy cannula may occur in the trachea. Inflammation and newly formed granulation tissue result in severe stenosis in the airways. During surgical treatment of such patients, airway management is important. In this case report, we will discuss gas exchange and airway management with jet ventilation (JV) during excision of the granulation tissue with endolaryngeal laser surgery, leading to subglottic stenosis in tracheostomised patients in WG. PMID:27366530

  4. 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

  5. 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

  6. Mechanically patterning the embryonic airway epithelium

    PubMed Central

    Varner, Victor D.; Gleghorn, Jason P.; Miller, Erin; Radisky, Derek C.; Nelson, Celeste M.

    2015-01-01

    Collections of cells must be patterned spatially during embryonic development to generate the intricate architectures of mature tissues. In several cases, including the formation of the branched airways of the lung, reciprocal signaling between an epithelium and its surrounding mesenchyme helps generate these spatial patterns. Several molecular signals are thought to interact via reaction-diffusion kinetics to create distinct biochemical patterns, which act as molecular precursors to actual, physical patterns of biological structure and function. Here, however, we show that purely physical mechanisms can drive spatial patterning within embryonic epithelia. Specifically, we find that a growth-induced physical instability defines the relative locations of branches within the developing murine airway epithelium in the absence of mesenchyme. The dominant wavelength of this instability determines the branching pattern and is controlled by epithelial growth rates. These data suggest that physical mechanisms can create the biological patterns that underlie tissue morphogenesis in the embryo. PMID:26170292

  7. Mechanically patterning the embryonic airway epithelium.

    PubMed

    Varner, Victor D; Gleghorn, Jason P; Miller, Erin; Radisky, Derek C; Nelson, Celeste M

    2015-07-28

    Collections of cells must be patterned spatially during embryonic development to generate the intricate architectures of mature tissues. In several cases, including the formation of the branched airways of the lung, reciprocal signaling between an epithelium and its surrounding mesenchyme helps generate these spatial patterns. Several molecular signals are thought to interact via reaction-diffusion kinetics to create distinct biochemical patterns, which act as molecular precursors to actual, physical patterns of biological structure and function. Here, however, we show that purely physical mechanisms can drive spatial patterning within embryonic epithelia. Specifically, we find that a growth-induced physical instability defines the relative locations of branches within the developing murine airway epithelium in the absence of mesenchyme. The dominant wavelength of this instability determines the branching pattern and is controlled by epithelial growth rates. These data suggest that physical mechanisms can create the biological patterns that underlie tissue morphogenesis in the embryo. PMID:26170292

  8. 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

  9. Nonlinear Compliance Modulates Dynamic Bronchoconstriction in a Multiscale Airway Model

    PubMed Central

    Hiorns, Jonathan E.; Jensen, Oliver E.; Brook, Bindi S.

    2014-01-01

    The role of breathing and deep inspirations (DI) in modulating airway hyperresponsiveness remains poorly understood. In particular, DIs are potent bronchodilators of constricted airways in nonasthmatic subjects but not in asthmatic subjects. Additionally, length fluctuations (mimicking DIs) have been shown to reduce mean contractile force when applied to airway smooth muscle (ASM) cells and tissue strips. However, these observations are not recapitulated on application of transmural pressure (PTM) oscillations (that mimic tidal breathing and DIs) in isolated intact airways. To shed light on this paradox, we have developed a biomechanical model of the intact airway, accounting for strain-stiffening due to collagen recruitment (a large component of the extracellular matrix (ECM)), and dynamic actomyosin-driven force generation by ASM cells. In agreement with intact airway studies, our model shows that PTM fluctuations at particular mean transmural pressures can lead to only limited bronchodilation. However, our model predicts that moving the airway to a more compliant point on the static pressure-radius relationship (which may involve reducing mean PTM), before applying pressure fluctuations, can generate greater bronchodilation. This difference arises from competition between passive strain-stiffening of ECM and force generation by ASM yielding a highly nonlinear relationship between effective airway stiffness and PTM, which is modified by the presence of contractile agonist. Effectively, the airway at its most compliant may allow for greater strain to be transmitted to subcellular contractile machinery. The model predictions lead us to hypothesize that the maximum possible bronchodilation of an airway depends on its static compliance at the PTM about which the fluctuations are applied. We suggest the design of additional experimental protocols to test this hypothesis. PMID:25517167

  10. 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

  11. Influence of airway wall stiffness and parenchymal tethering on the dynamics of bronchoconstriction

    PubMed Central

    Khan, Mohammad Afzal; Ellis, Russ; Inman, Mark D.; Bates, Jason H. T.; Sanderson, Michael J.

    2010-01-01

    Understanding how tissue remodeling affects airway responsiveness is of key importance, but experimental data bearing on this issue remain scant. We used lung explants to investigate the effects of enzymatic digestion on the rate and magnitude of airway narrowing induced by acetylcholine. To link the observed changes in narrowing dynamics to the degree of alteration in tissue mechanics, we compared our experimental results with predictions made by a computational model of a dynamically contracting elastic airway embedded in elastic parenchyma. We found that treatment of explanted airways with two different proteases (elastase and collagenase) resulted in differential effects on the dynamics of airway narrowing following application of ACh. Histological corroboration of these different effects is manifest in different patterns of elimination of collagen and elastin from within the airway wall and the surrounding parenchyma. Simulations with a computational model of a dynamically contracting airway embedded in elastic parenchyma suggest that elastase exerts its functional effects predominately through a reduction in parenchymal tethering, while the effects of collagenase are more related to a reduction in airway wall stiffness. We conclude that airway and parenchymal remodeling as a result of protease activity can have varied effects on the loads opposing ASM shortening, with corresponding consequences for airway responsiveness. PMID:20435686

  12. 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

  13. Three-dimensional reconstruction of upper airways from MDCT

    NASA Astrophysics Data System (ADS)

    Perchet, Diane; Fetita, Catalin; Preteux, Francoise

    2005-03-01

    Under the framework of clinical respiratory investigation, providing accurate modalities for morpho-functional analysis is essential for diagnosis improvement, surgical planning and follow-up. This paper focuses on the upper airways investigation and develops an automated approach for 3D mesh reconstruction from MDCT acquisitions. In order to overcome the difficulties related to the complex morphology of the upper airways and to the image gray level heterogeneity of the airway lumens and thin bony septa, the proposed 3D reconstruction methodology combines 2D segmentation and 3D surface regularization approaches. The segmentation algorithm relies on mathematical morphology theory and provides airway lumen robust discrimination from the surrounding tissues, while preserving the connectivity relationship between the different anatomical structures. The 3D regularization step uses an energy-based modeling in order to achieve a smooth and well-fitted 3D surface of the upper airways. An accurate 3D mesh representation of the reconstructed airways makes it possible to develop specific clinical applications such as virtual endoscopy, surgical planning and computer assisted intervention. In addition, building up patient-specific 3D models of upper airways is highly valuable for the study and design of inhaled medication delivery via computational fluid dynamics (CFD) simulations.

  14. 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

  15. 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.

  16. 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

  17. 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

  18. 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

  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. A computational prediction for the effective drug and stem cell treatment of human airway burns.

    PubMed

    Park, Seungman

    2016-08-01

    Burns in the airway from inhaling hot gases lead to one of the most common causes of death in the United States. In order to navigate tissues with large burn areas, the velocity, temperature, and heat flux distributions throughout the human airway system are computed for the inhalation of hot air using the finite-element method. From there, the depth of burned tissue is estimated for a range of exposure times. Additionally, the effectiveness of drug or stem cell delivery to the burned airway tissue is considered for a range of drug or cell sizes. Results showed that the highest temperature and lowest heat flux regions are observed near the pharynx and just upstream of the glottis. It was found that large particles such as stem cells (>20 μm) are effective for treatment of the upper airways, whereas small particles (<10 μm) such as drug nanoparticles are effective in the lower airways. PMID:26513000

  1. Bacterial tracheobronchitis. A rare cause of adult airway stenosis.

    PubMed

    Kadowaki, Toru; Hamada, Hironobu; Fujiwara, Ai; Miyoshi, Seigo; Hamaguchi, Naohiko; Ito, Ryoji; Higaki, Jitsuo

    2009-11-01

    Bacterial tracheobronchitis is a rare cause of airway stenosis in adults. This report describes a 73-year-old woman with a recent history of polysialadenitis, who presented with severe airway obstruction due to infection and stenosis of tracheal and bronchial tissue. Tissue culture of the bronchial mucosa showed growth of methicillin resistant Staphylococcus epidermidis (MRSE). Sputum culture showed growth of MRSE, Pseudomonas aeruginosa, Enterobacter cloacae and Enterococcus faecalis; the same organisms were cultured from the salivary glands. Tracheostomy and antibiotic therapy were effective in controlling the disease. PMID:19818053

  2. Airway Injury from Initiating Ventilation in Preterm Sheep

    PubMed Central

    Hillman, Noah H.; Kallapur, Suhas G.; Pillow, J. Jane; Moss, Timothy J. M.; Polglase, Graeme R.; Nitsos, Ilias; Jobe, Alan H.

    2009-01-01

    Premature infants exposed to ventilation are at risk of developing bronchopulmonary dysplasia (BPD) and persistent lung disease in childhood. We report where injury occurred within the lung following brief ventilation at birth. Preterm sheep (129d gestation) were ventilated with an escalating VT to 15mL/kg by 15 min to injure the lungs, with the placental circulation intact (Fetal) or after delivery (Newborn). Fetal lambs were returned to the uterus for 2h 45min, while Newborn lambs were maintained with gentle ventilatory support for the same period. The control group was not ventilated. Bronchoalveolar lavage fluid (BALF) and lung tissue were analysed. In both Fetal and Newborn lambs, ventilation caused bronchial epithelial disruption in medium-sized airways. Egr-1, MCP-1, IL-6, and IL-1β mRNA increased in lung tissue from Fetal and Newborn lambs. Egr-1, MCP-1 and IL-6 mRNA were induced in mesenchymal cells surrounding small airways, whereas IL-1β mRNA localized to the epithelium of medium/small airways. Ventilation caused loss of HSP70 mRNA from the bronchial epithelium, but induced mRNA in smooth muscle surrounding large airways. HSP70 protein decreased in lung tissue and increased in BALF with ventilation. Initiation of ventilation induced a stress response and inflammatory cytokines in small and medium-sized airways. PMID:19816239

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. Repeated allergen exposure reduce early phase airway response and leukotriene release despite upregulation of 5-lipoxygenase pathways

    PubMed Central

    2012-01-01

    Background Allergen induced early phase airway response and airway plasma exudation are predominantly mediated by inflammatory mast cell mediators including histamine, cysteinyl leukotrienes (cysLTs) and thromboxane A2 (TXA2). The aim of the present study was to evaluate whether repeated allergen exposure affects early phase airway response to allergen challenge. Methods A trimellitic anhydride (TMA) sensitized guinea pig model was used to investigate the effects of low dose repeated allergen exposure on cholinergic airway responsiveness, early phase airway response and plasma exudation, as well as local airway production of mast cell derived cysteinyl leukotrienes and thromboxane B2 (TXB2) after allergen challenge. Results Repeated low dose allergen exposure increased cholinergic airway responsiveness. In contrast, early phase airway response and plasma exudation in response to a high-dose allergen challenge were strongly attenuated after repeated low dose allergen exposure. Inhibition of the airway response was unspecific to exposed allergen and independent of histamine receptor blocking. Furthermore, a significant reduction of cysteinyl leukotrienes and TXB2 was found in the airways of animals repeatedly exposed to a low dose allergen. However, in vitro stimulation of airway tissue from animals repeatedly exposed to a low dose allergen with arachidonic acid and calcium ionophore (A23187) induced production of cysteinyl leukotrienes and TXB2, suggesting enhanced activity of 5-lipoxygenase and cyclooxygenase pathways. Conclusions The inhibition of the early phase airway response, cysteinyl leukotriene and TXB2 production after repeated allergen exposure may result from unresponsive effector cells. PMID:22439792

  10. Temporal Monitoring of Differentiated Human Airway Epithelial Cells Using Microfluidics

    PubMed Central

    Blume, Cornelia; Reale, Riccardo; Held, Marie; Millar, Timothy M.; Collins, Jane E.; Davies, Donna E.; Morgan, Hywel; Swindle, Emily J.

    2015-01-01

    The airway epithelium is exposed to a variety of harmful agents during breathing and appropriate cellular responses are essential to maintain tissue homeostasis. Recent evidence has highlighted the contribution of epithelial barrier dysfunction in the development of many chronic respiratory diseases. Despite intense research efforts, the responses of the airway barrier to environmental agents are not fully understood, mainly due to lack of suitable in vitro models that recapitulate the complex in vivo situation accurately. Using an interdisciplinary approach, we describe a novel dynamic 3D in vitro model of the airway epithelium, incorporating fully differentiated primary human airway epithelial cells at the air-liquid interface and a basolateral microfluidic supply of nutrients simulating the interstitial flow observed in vivo. Through combination of the microfluidic culture system with an automated fraction collector the kinetics of cellular responses by the airway epithelium to environmental agents can be analysed at the early phases for the first time and with much higher sensitivity compared to common static in vitro models. Following exposure of primary differentiated epithelial cells to pollen we show that CXCL8/IL–8 release is detectable within the first 2h and peaks at 4–6h under microfluidic conditions, a response which was not observed in conventional static culture conditions. Such a microfluidic culture model is likely to have utility for high resolution temporal profiling of toxicological and pharmacological responses of the airway epithelial barrier, as well as for studies of disease mechanisms. PMID:26436734

  11. Temporal Monitoring of Differentiated Human Airway Epithelial Cells Using Microfluidics.

    PubMed

    Blume, Cornelia; Reale, Riccardo; Held, Marie; Millar, Timothy M; Collins, Jane E; Davies, Donna E; Morgan, Hywel; Swindle, Emily J

    2015-01-01

    The airway epithelium is exposed to a variety of harmful agents during breathing and appropriate cellular responses are essential to maintain tissue homeostasis. Recent evidence has highlighted the contribution of epithelial barrier dysfunction in the development of many chronic respiratory diseases. Despite intense research efforts, the responses of the airway barrier to environmental agents are not fully understood, mainly due to lack of suitable in vitro models that recapitulate the complex in vivo situation accurately. Using an interdisciplinary approach, we describe a novel dynamic 3D in vitro model of the airway epithelium, incorporating fully differentiated primary human airway epithelial cells at the air-liquid interface and a basolateral microfluidic supply of nutrients simulating the interstitial flow observed in vivo. Through combination of the microfluidic culture system with an automated fraction collector the kinetics of cellular responses by the airway epithelium to environmental agents can be analysed at the early phases for the first time and with much higher sensitivity compared to common static in vitro models. Following exposure of primary differentiated epithelial cells to pollen we show that CXCL8/IL-8 release is detectable within the first 2h and peaks at 4-6h under microfluidic conditions, a response which was not observed in conventional static culture conditions. Such a microfluidic culture model is likely to have utility for high resolution temporal profiling of toxicological and pharmacological responses of the airway epithelial barrier, as well as for studies of disease mechanisms. PMID:26436734

  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. 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

  14. Immunolocalization of NLRP3 Inflammasome in Normal Murine Airway Epithelium and Changes following Induction of Ovalbumin-Induced Airway Inflammation.

    PubMed

    Tran, Hai B; Lewis, Martin D; Tan, Lor Wai; Lester, Susan E; Baker, Leonie M; Ng, Jia; Hamilton-Bruce, Monica A; Hill, Catherine L; Koblar, Simon A; Rischmueller, Maureen; Ruffin, Richard E; Wormald, Peter J; Zalewski, Peter D; Lang, Carol J

    2012-01-01

    Little is known about innate immunity and components of inflammasomes in airway epithelium. This study evaluated immunohistological evidence for NLRP3 inflammasomes in normal and inflamed murine (Balb/c) airway epithelium in a model of ovalbumin (OVA) induced allergic airway inflammation. The airway epithelium of control mice exhibited strong cytoplasmic staining for total caspase-1, ASC, and NLRP3, whereas the OVA mice exhibited strong staining for active caspase-1, with redistribution of caspase-1, IL-1β and IL-18, indicating possible activation of the NLRP3 inflammasome. Active caspase-1, NLRP3, and other inflammasome components were also detected in tissue eosinophils from OVA mice, and may potentially contribute to IL-1β and IL-18 production. In whole lung, inRNA expression of NAIP and procaspase-1 was increased in OVA mice, whereas NLRP3, IL-1β and IL-18 decreased. Some OVA-treated mice also had significantly elevated and tightly correlated serum levels of IL-1β and TNFα. In cultured normal human bronchial epithelial cells, LPS priming resulted in a significant increase in NLRP3 and II-lp protein expression. This study is the first to demonstrate NLRP3 inflammasome components in normal airway epithelium and changes with inflammation. We propose activation and/or luminal release of the inflammasome is a feature of allergic airway inflammation which may contribute to disease pathogenesis. PMID:22523501

  15. Human airway epithelia express catalytically active NEU3 sialidase

    PubMed Central

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

    2014-01-01

    Sialic acids on glycoconjugates play a pivotal role in many biological processes. In the airways, sialylated glycoproteins and glycolipids are strategically positioned on the plasma membranes of epithelia to regulate receptor-ligand, cell-cell, and host-pathogen interactions at the molecular level. We now demonstrate, for the first time, sialidase activity for ganglioside substrates in human airway epithelia. Of the four known mammalian sialidases, NEU3 has a substrate preference for gangliosides and is expressed at mRNA and protein levels at comparable abundance in epithelia derived from human trachea, bronchi, small airways, and alveoli. In small airway and alveolar epithelia, NEU3 protein was immunolocalized to the plasma membrane, cytosolic, and nuclear subcellular fractions. Small interfering RNA-induced silencing of NEU3 expression diminished sialidase activity for a ganglioside substrate by >70%. NEU3 immunostaining of intact human lung tissue could be localized to the superficial epithelia, including the ciliated brush border, as well as to nuclei. However, NEU3 was reduced in subepithelial tissues. These results indicate that human airway epithelia express catalytically active NEU3 sialidase. PMID:24658138

  16. 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...

  17. 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...

  18. Observing planar cell polarity in multiciliated mouse airway epithelial cells

    PubMed Central

    Vladar, Eszter K.; Lee, Yin Loon; Stearns, Tim; Axelrod, Jeffrey D.

    2015-01-01

    The concerted movement of cilia propels inhaled contaminants out of the lungs, safeguarding the respiratory system from toxins, pathogens, pollutants, and allergens. Motile cilia on the multiciliated cells (MCCs) of the airway epithelium are physically oriented along the tissue axis for directional motility, which depends on the planar cell polarity (PCP) signaling pathway. The MCCs of the mouse respiratory epithelium have emerged as an important model for the study of motile ciliogenesis and the PCP signaling mechanism. Unlike other motile ciliated or planar polarized tissues, airway epithelial cells are relatively easily accessible and primary cultures faithfully model many of the essential features of the in vivo tissue. There is growing interest in understanding how cells acquire and polarize motile cilia due to the impact of mucociliary clearance on respiratory health. Here, we present methods for observing and quantifying the planar polarized orientation of motile cilia both in vivo and in primary culture airway epithelial cells. We describe how to acquire and evaluate electron and light microscopy images of ciliary ultrastructural features that reveal planar polarized orientation. Furthermore, we describe the immunofluorescence localization of PCP pathway components as a simple readout for airway epithelial planar polarization and ciliary orientation. These methods can be adapted to observe ciliary orientation in other multi- and monociliated cells and to detect PCP pathway activity in any tissue or cell type. PMID:25837385

  19. 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

  20. 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.

  1. 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

  2. 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

  3. 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

  4. 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

  5. Exploratory study into the effect of abdominal mass loading on airways resistance and ventilatory failure

    PubMed Central

    Dattani, Raj S; Swerner, Casey B; Stradling, John R; Manuel, Ari RG

    2016-01-01

    Objective We hypothesised that the airway resistance during tidal breathing would correlate with a particular pattern of increasing obesity, particularly when supine, and would differ between participants with and without ventilatory failure. Methods In our cross-sectional cohort study, 72 morbidly obese patients (40 males, 32 females, mean body mass index (BMI) 47.2) had measurements of both airways resistance (by impulse oscillometry (IOS)) and adiposity (by dual-energy X-ray absorptiometry (DXA)). Results All measures of airways resistance increased in the supine position: total airways resistance (R5) +37% (p<0.0005); large airways resistance (R20) +29% (p<0.0005); and small airways resistance (R5–R20) +52% (p<0.0005). BMI was correlated with seated R5, seated R5–R20, supine R5 and supine R5–R20 (r=0.33 p<0.006, r=0.32 p<0.004, r=0.30 p<0.02 and r=0.36 p<0.04, respectively). Visceral adipose tissue mass was correlated with supine R5–20 (r=0.46 p<0.05). Supine measures of total airways resistance (R5) and large airways resistance (R20) differed between those with and without ventilatory failure, as did mean weight and BMI. Conclusions Our study identifies a potentially detrimental effect of the supine posture on tidal breathing airways resistance in obese patients. This change is correlated most with visceral adipose tissue mass and the small airways. We were able to demonstrate that supine increases in airways resistance during tidal breathing, within obese patients, are different between those with and without ventilatory failure. Trial registration number NCT01380418; pre-results. PMID:27335651

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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.

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. [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

  17. Cigarette smoke increases the penetration of asbestos fibers into airway walls

    SciTech Connect

    McFadden, D.; Wright, J.; Wiggs, B.; Churg, A.

    1986-04-01

    For study of the penetration of asbestos fibers into airway walls, guinea pigs were given amosite asbestos by intratracheal instillation. Half of the animals were also exposed to cigarette smoke. Animals were sacrificed at 1 week and 1 month, and numbers of fibers in airway walls were counted in histologic sections. In both smoke-exposed and nonexposed groups, numbers of fibers per square millimeter of airway wall increased from 1 week to 1 month in the respiratory bronchioles. At each time period, smoke-exposed animals had significantly higher numbers of fibers in the airway walls, compared with nonexposed animals. It is concluded that 1) continued transport of fibers into interstitial tissues may be the reason that asbestosis can progress after cessation of exposure; 2) cigarette smoke increases the penetration of fibers into airway walls. This effect may play a role in the increased incidence of disease seen in smoking, compared with nonsmoking, asbestos workers.

  18. Cigarette smoke increases the penetration of asbestos fibers into airway walls.

    PubMed Central

    McFadden, D.; Wright, J.; Wiggs, B.; Churg, A.

    1986-01-01

    For study of the penetration of asbestos fibers into airway walls, guinea pigs were given amosite asbestos by intratracheal instillation. Half of the animals were also exposed to cigarette smoke. Animals were sacrificed at 1 week and 1 month, and numbers of fibers in airway walls were counted in histologic sections. In both smoke-exposed and nonexposed groups, numbers of fibers per square millimeter of airway wall increased from 1 week to 1 month in the respiratory bronchioles. At each time period, smoke-exposed animals had significantly higher numbers of fibers in the airway walls, compared with nonexposed animals. It is concluded that 1) continued transport of fibers into interstitial tissues may be the reason that asbestosis can progress after cessation of exposure; 2) cigarette smoke increases the penetration of fibers into airway walls. This effect may play a role in the increased incidence of disease seen in smoking, compared with nonsmoking, asbestos workers. PMID:3963152

  19. Transbronchial biopsy as a tool to evaluate small airways in asthma.

    PubMed

    Balzar, S; Wenzel, S E; Chu, H W

    2002-08-01

    Small airway (SA) inflammation in asthmatics is poorly understood. Surgical biopsies to obtain peripheral lung tissue are seldom justified in asthmatics. Therefore, the authors hypothesised that transbronchial biopsy could be an alternative approach to evaluate SA in asthma. Transbronchial and endobronchial biopsy tissue samples (TBBX and EBBX) from 12 severe asthmatics were evaluated for airway and parenchymal total inflammatory cell count expressed as the sum of immunostained T-cells (CD3), macrophages (CD68), mast cells (tryptase AAI), neutrophils (neutrophil elastase) and eosinophils (EG2) per mm2. The large airways (LA) were evaluated in EBBXs, while SA, medium airways (MA) and alveolar tissue (AT) were evaluated in TBBXs. When cell counts from SA, MA, LA and AT were compared, SA had a significantly higher cell count than MA or LA (SA 1011 x mm(-2) (539-1,290), MA 346 x mm(-2) (223-415), LA 332 x mm(-2) (189-416), AT 464 x mm(-2) (298-834)). The cell density and pattern of the inflammatory cell distribution in subjects with TBBXs appeared similar to those in three severe asthmatics whose inflammatory cells were analysed in surgical tissue samples. This study suggests that small airway may be identified and analysed in transbronchial biopsy tissue samples and therefore transbronchial biopsy tissue samples could expand the analysis of inflammation and tissue remodelling in asthma. PMID:12212952

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. Effect of P2X4R on airway inflammation and airway remodeling in allergic airway challenge in mice

    PubMed Central

    CHEN, HONGXIA; XIA, QINGQING; FENG, XIAOQIAN; CAO, FANGYUAN; YU, HANG; SONG, YINLI; NI, XIUQIN

    2016-01-01

    P2X4 receptor (P2X4R) is the most widely expressed subtype of the P2XRs in the purinergic receptor family. Adenosine triphosphate (ATP), a ligand for this receptor, has been implicated in the pathogenesis of asthma. ATP-P2X4R signaling is involved in pulmonary vascular remodeling, and in the proliferation and differentiation of airway and alveolar epithelial cell lines. However, the role of P2X4R in asthma remains to be elucidated. This aim of the present study was to investigate the effects of P2X4R in a murine experimental asthma model. The asthmatic model was established by the inhalation of ovalbumin (OVA) in BALB/c mice. The mice were treated with P2X4R-specific agonists and antagonists to investigate the role of this receptor in vivo. Pathological changes in the bronchi and lung tissues were examined using hematoxylin and eosin staining, Masson's trichrome staining and Alcian blue staining. The inflammatory cells in the bronchoalveolar lavage fluid were counted, and the expression levels of P2X4R, α-smooth muscle actin (α-SMA) and proliferating cell nuclear antigen (PCNA) were detected using western blotting. In the OVA-challenged mice, inflammation, infiltration, collagen deposition, mucus production, and the expression levels of P2X4R and PCNA were all increased; however, the expression of α-SMA was decreased, compared with the mice in the control group. Whereas treatment with the P2X4R agonist, ATP, enhanced the allergic reaction, treatment with the P2X4R antagonist, 5-BDBD, attenuated the allergic reaction. The results suggested that ATP-P2X4R signaling may not only contribute to airway inflammation, but it may also contribute to airway remodeling in allergic asthma in mice. PMID:26648454

  9. Airway management evolution - in a search for an ideal extraglottic airway device.

    PubMed

    Michálek, Pavel; Miller, Donald M

    2014-01-01

    Extraglottic airway devices (EADs) are commonly used equipment for airway maintenance during elective procedures under general anaesthesia. They may be used also in other indications such as conduit for tracheal intubation or rescue airway device in prehospital medicine. Current classifications of the EADs lack systematic approach and therefore classification according to the sealing sites and sealing mechanisms is suggested in this review article. Modern EADs are disposable, latex-free devices made of plastic materials most commonly from polyvinylchloride (PVC). The bowl of uncuffed sealers is manufactured from different materials such as thermoplastic elastomers or ethylene-vinyl-acetate co-polymer. EADs create various physical forces exerted on the adjacent tissues which may contribute to different sealing characteristic of particular device or to variable incidence of postoperative complications. Desired features of an ideal EAD involve easy insertion, high insertion success rate even by inexperienced users, protection against aspiration of gastric contents and low incidence of postoperative complications such as sore throat, hoarseness, cough or swallowing difficulties. PMID:25626328

  10. 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

  11. 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

  12. Relationship between Body Fat Distribution and Upper Airway Dynamic Function during Sleep in Adolescents

    PubMed Central

    Yuan, Haibo; Schwab, Richard J.; Kim, Christopher; He, Jiwei; Shults, Justine; Bradford, Ruth; Huang, Jingtao; Marcus, Carole L.

    2013-01-01

    Introduction: The obstructive sleep apnea syndrome (OSAS) is associated with increased visceral adipose tissue (VAT) in adults; however, few studies have evaluated VAT in relation to upper airway function in adolescents. We hypothesized that increased neck circumference (NC) and VAT would be associated with increased upper airway collapsibility. Methods: Adolescents (24 obese patients with OSAS, 22 obese control patients, and 29 lean control patients) underwent abdominal magnetic resonance imaging, and measurement of upper airway pressure-flow relationships in the activated and hypotonic upper airway states. Results: Patients with OSAS had a greater activated slope of the pressure-flow relationship (SPF) than control groups (P < 0.001), whereas hypotonic SPF was greater in both obese groups compared with lean control patients (P = 0.01). NC and VAT were greater in obese control patients and those with OSAS than in lean control patients (P < 0.001), but did not differ between obese patients with OSAS and obese control patients. In lean control patients and those with OSAS, increased NC was associated with increased activated SPF, whereas in obese control patients it was associated with decreased activated SPF (P = 0.03). In contrast, increased NC was associated with increased hypotonic SPF in all groups (P < 0.001). There was no significant effect of VAT on either activated or hypotonic SPF for any of the three groups. Conclusions: Increased neck circumference was associated with increased upper airway collapsibility in adolescents in the hypotonic but not activated state. These data suggest that obese adolescents without OSAS, despite a narrowed upper airway from adipose tissue, are protected from developing OSAS by upper airway neuromotor activation. Neither neck circumference nor visceral adipose tissue is useful in predicting upper airway collapsibility in obese adolescents. Citation: Yuan H; Schwab RJ; Kim C; He J; Shults J; Bradford R; Huang J; Marcus CL

  13. Genomic Landscape Established by Allelic Imbalance in the Cancerization Field of a Normal Appearing Airway.

    PubMed

    Jakubek, Yasminka; Lang, Wenhua; Vattathil, Selina; Garcia, Melinda; Xu, Li; Huang, Lili; Yoo, Suk-Young; Shen, Li; Lu, Wei; Chow, Chi-Wan; Weber, Zachary; Davies, Gareth; Huang, Jing; Behrens, Carmen; Kalhor, Neda; Moran, Cesar; Fujimoto, Junya; Mehran, Reza; El-Zein, Randa; Swisher, Stephen G; Wang, Jing; Fowler, Jerry; Spira, Avrum E; Ehli, Erik A; Wistuba, Ignacio I; Scheet, Paul; Kadara, Humam

    2016-07-01

    Visually normal cells adjacent to, and extending from, tumors of the lung may carry molecular alterations characteristics of the tumor itself, an effect referred to as airway field of cancerization. This airway field has been postulated as a model for early events in lung cancer pathogenesis. Yet the genomic landscape of somatically acquired molecular alterations in airway epithelia of lung cancer patients has remained unknown. To begin to fill this void, we sought to comprehensively characterize the genomic architecture of chromosomal alterations inducing allelic imbalance (AI) in the airway field of the most common type of lung tumors, non-small cell lung cancer (NSCLC). To do so, we conducted a genome-wide survey of multiple spatially distributed normal-appearing airways, multiregion tumor specimens, and uninvolved normal tissues or blood from 45 patients with early-stage NSCLC. We detected alterations in airway epithelia from 22 patients, with an increased frequency in NSCLCs of squamous histology. Our data also indicated a spatial gradient of AI in samples at closer proximity to the NSCLC. Chromosome 9 displayed the highest levels of AI and comprised recurrent independent events. Furthermore, the airway field AI included oncogenic gains and tumor suppressor losses in known NSCLC drivers. Our results demonstrate that genome-wide AI is common in the airway field of cancerization, providing insights into early events in the pathogenesis of NSCLC that may comprise targets for early treatment and chemoprevention. Cancer Res; 76(13); 3676-83. ©2016 AACR. PMID:27216194

  14. 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.

  15. Intratracheal Administration of Mesenchymal Stem Cells Modulates Tachykinin System, Suppresses Airway Remodeling and Reduces Airway Hyperresponsiveness in an Animal Model

    PubMed Central

    Spaziano, Giuseppe; Piegari, Elena; Matteis, Maria; Cappetta, Donato; Esposito, Grazia; Russo, Rosa; Tartaglione, Gioia; De Palma, Raffaele; Rossi, Francesco; D’Agostino, Bruno

    2016-01-01

    Background The need for new options for chronic lung diseases promotes the research on stem cells for lung repair. Bone marrow-derived mesenchymal stem cells (MSCs) can modulate lung inflammation, but the data on cellular processes involved in early airway remodeling and the potential involvement of neuropeptides are scarce. Objectives To elucidate the mechanisms by which local administration of MSCs interferes with pathophysiological features of airway hyperresponsiveness in an animal model. Methods GFP-tagged mouse MSCs were intratracheally delivered in the ovalbumin mouse model with subsequent functional tests, the analysis of cytokine levels, neuropeptide expression and histological evaluation of MSCs fate and airway pathology. Additionally, MSCs were exposed to pro-inflammatory factors in vitro. Results Functional improvement was observed after MSC administration. Although MSCs did not adopt lung cell phenotypes, cell therapy positively affected airway remodeling reducing the hyperplastic phase of the gain in bronchial smooth muscle mass, decreasing the proliferation of epithelium in which mucus metaplasia was also lowered. Decrease of interleukin-4, interleukin-5, interleukin-13 and increase of interleukin-10 in bronchoalveolar lavage was also observed. Exposed to pro-inflammatory cytokines, MSCs upregulated indoleamine 2,3-dioxygenase. Moreover, asthma-related in vivo upregulation of pro-inflammatory neurokinin 1 and neurokinin 2 receptors was counteracted by MSCs that also determined a partial restoration of VIP, a neuropeptide with anti-inflammatory properties. Conclusion Intratracheally administered MSCs positively modulate airway remodeling, reduce inflammation and improve function, demonstrating their ability to promote tissue homeostasis in the course of experimental allergic asthma. Because of a limited tissue retention, the functional impact of MSCs may be attributed to their immunomodulatory response combined with the interference of neuropeptide

  16. 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

  17. Upper airway obstruction in a patient with Ehlers-Danlos syndrome.

    PubMed

    Chatzoudis, D; Kelly, T J; Lancaster, J; Jones, T M

    2015-04-01

    We report a case of recurrent airway obstruction episodes resulting from laryngeal hypermobility in a patient with Ehlers-Danlos syndrome. A 44-year-old woman, with known Ehlers-Danlos syndrome, presented with recent onset of episodes of upper airway obstruction due to hypermobility of her larynx. A suitable conservative management strategy proved elusive and the patient finally underwent a thyrohyoidopexy. The patient remains symptom free nine months after the procedure. This is the first report of spontaneous life threatening upper airway obstruction due to hypermobility of the suprahyoid suspensory soft tissues in Ehlers-Danlos syndrome. PMID:26263828

  18. 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

  19. 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

  20. "Live cadavers" for practicing airway management.

    PubMed

    Aboud, Emad T; Aboud, Ghaith; Aboud, Talal

    2015-03-01

    Human cadavers have been used successfully as training models to practice airway management, but the lack of lifelike conditions reduces the utility of this model when softness of tissue and the ability to bleed are required for training scenarios. This report describes our "live cadaver" model, which combines lifelike conditions with real human anatomy. Five human cadavers were prepared as "live cadavers". This entailed cannulating the carotid and femoral arteries and the jugular and femoral veins, and then connected them to artificial blood reservoirs. An intra-aortic balloon pump was used to provide pulsating flow through the heart and major arteries. Finally, central and peripheral lines were inserted. Multiple techniques related to airway management were practiced in setting simulating the treatment of casualties with multiple trauma to include emergency cricothyroidotomy. With this model, participants were confronted with medical situations similar to those found in traumatized live patients (e.g., blood and other body fluids filling the mouth and nose, edema of the tongue and face). With the combination of lifelike conditions and real human anatomy, our experience demonstrated that the "live cadaver" increased the training value of traditionally prepared cadaver models. PMID:25747648

  1. 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

  2. Enlargement of the lateral pharyngeal fat pad space in pigs increases upper airway resistance.

    PubMed

    Winter, W C; Gampper, T; Gay, S B; Suratt, P M

    1995-09-01

    Because the upper airway is partially enclosed in a rigid boundary, enlargement of soft tissue structures within this boundary could narrow the airway. The purpose of this study was to determine whether enlargement of the soft tissue space in the region of the lateral pharyngeal fat pad would increase pharyngeal resistance and narrow the retropalateal upper airway. In five young male anesthetized pigs, we inserted balloon occlusion catheters in the lateral pharyngeal fat pad under computerized tomographic scan guidance. We measured pharyngeal resistance with a pharyngeal catheter and a tightly fitting face mask before and after inflation of the balloons. We also measured pharyngeal airway cross-sectional area before and after inflation of the balloons. In all pigs, balloon inflation significantly increased pharyngeal resistance and significantly decreased the area of the retropalateal airway. We conclude that enlargement of the soft tissue space in the region of the lateral pharyngeal fat pad increases pharyngeal resistance and narrows the retropalateal airway in anesthetized pigs. PMID:8567510

  3. 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

  4. 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

  5. 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

  6. 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

  7. Matrix stiffness-modulated proliferation and secretory function of the airway smooth muscle cells.

    PubMed

    Shkumatov, Artem; Thompson, Michael; Choi, Kyoung M; Sicard, Delphine; Baek, Kwanghyun; Kim, Dong Hyun; Tschumperlin, Daniel J; Prakash, Y S; Kong, Hyunjoon

    2015-06-01

    Multiple pulmonary conditions are characterized by an abnormal misbalance between various tissue components, for example, an increase in the fibrous connective tissue and loss/increase in extracellular matrix proteins (ECM). Such tissue remodeling may adversely impact physiological function of airway smooth muscle cells (ASMCs) responsible for contraction of airways and release of a variety of bioactive molecules. However, few efforts have been made to understand the potentially significant impact of tissue remodeling on ASMCs. Therefore, this study reports how ASMCs respond to a change in mechanical stiffness of a matrix, to which ASMCs adhere because mechanical stiffness of the remodeled airways is often different from the physiological stiffness. Accordingly, using atomic force microscopy (AFM) measurements, we found that the elastic modulus of the mouse bronchus has an arithmetic mean of 23.1 ± 14 kPa (SD) (median 18.6 kPa). By culturing ASMCs on collagen-conjugated polyacrylamide hydrogels with controlled elastic moduli, we found that gels designed to be softer than average airway tissue significantly increased cellular secretion of vascular endothelial growth factor (VEGF). Conversely, gels stiffer than average airways stimulated cell proliferation, while reducing VEGF secretion and agonist-induced calcium responses of ASMCs. These dependencies of cellular activities on elastic modulus of the gel were correlated with changes in the expression of integrin-β1 and integrin-linked kinase (ILK). Overall, the results of this study demonstrate that changes in matrix mechanics alter cell proliferation, calcium signaling, and proangiogenic functions in ASMCs. PMID:25724668

  8. 3D mapping of airway wall thickening in asthma with MSCT: a level set approach

    NASA Astrophysics Data System (ADS)

    Fetita, Catalin; Brillet, Pierre-Yves; Hartley, Ruth; Grenier, Philippe A.; Brightling, Christopher

    2014-03-01

    Assessing the airway wall thickness in multi slice computed tomography (MSCT) as image marker for airway disease phenotyping such asthma and COPD is a current trend and challenge for the scientific community working in lung imaging. This paper addresses the same problem from a different point of view: considering the expected wall thickness-to-lumen-radius ratio for a normal subject as known and constant throughout the whole airway tree, the aim is to build up a 3D map of airway wall regions of larger thickness and to define an overall score able to highlight a pathological status. In this respect, the local dimension (caliber) of the previously segmented airway lumen is obtained on each point by exploiting the granulometry morphological operator. A level set function is defined based on this caliber information and on the expected wall thickness ratio, which allows obtaining a good estimate of the airway wall throughout all segmented lumen generations. Next, the vascular (or mediastinal dense tissue) contact regions are automatically detected and excluded from analysis. For the remaining airway wall border points, the real wall thickness is estimated based on the tissue density analysis in the airway radial direction; thick wall points are highlighted on a 3D representation of the airways and several quantification scores are defined. The proposed approach is fully automatic and was evaluated (proof of concept) on a patient selection coming from different databases including mild, severe asthmatics and normal cases. This preliminary evaluation confirms the discriminative power of the proposed approach regarding different phenotypes and is currently extending to larger cohorts.

  9. Allergen-induced airway remodeling is impaired in galectin-3 deficient mice1

    PubMed Central

    Ge, Xiao Na; Bahaie, Nooshin S.; Kang, Bit Na; Hosseinkhani, Reza M.; Ha, Sung Gil; Frenzel, Elizabeth M.; Liu, Fu-Tong; Rao, Savita P.; Sriramarao, P.

    2010-01-01

    The role played by the β-galactoside-binding lectin galectin-3 (Gal-3) in airway remodeling, a characteristic feature of asthma that leads to airway dysfunction and poor clinical outcome in humans, was investigated in a murine model of chronic allergic airway inflammation. Wild-type (WT) and Gal-3 knock-out (KO) mice were subjected to repetitive allergen challenge with ovalbumin (OVA) up to 12 weeks and bronchoalveolar lavage fluid (BALF) and lung tissue collected after the last challenge were evaluated for cellular features associated with airway remodeling. Compared to WT mice, chronic OVA challenge in Gal-3 KO mice resulted in diminished remodeling of the airways with significantly reduced mucus secretion, sub-epithelial fibrosis, smooth muscle thickness, and peribronchial angiogenesis. The higher degree of airway remodeling in WT mice was associated with higher Gal-3 expression in the BALF as well as lung tissue. Cell counts in BALF and lung immunohistology demonstrated that eosinophil infiltration in OVA-challenged Gal-3 KO mice was significantly reduced compared to WT mice. Evaluation of cellular mediators associated with eosinophil recruitment and airway remodeling revealed that levels of eotaxin-1, IL-5, IL-13, FIZZ1 and TGF-β were substantially lower in Gal-3 KO mice. Finally, leukocytes from Gal-3 KO mice demonstrated decreased trafficking (rolling) on vascular endothelial adhesion molecules compared to WT cells. Overall, these studies demonstrate that Gal-3 is an important lectin that promotes airway remodeling via airway recruitment of inflammatory cells, specifically eosinophils, and the development of a Th2 phenotype as well as increased expression of eosinophil-specific chemokines, pro-fibrogenic and angiogenic mediators. PMID:20543100

  10. Generation of airway epithelial cells with native characteristics from mouse induced pluripotent stem cells.

    PubMed

    Yoshie, Susumu; Imaizumi, Mitsuyoshi; Nakamura, Ryosuke; Otsuki, Koshi; Ikeda, Masakazu; Nomoto, Yukio; Wada, Ikuo; Omori, Koichi

    2016-05-01

    Airway epithelial cells derived from induced pluripotent stem (iPS) cells are expected to be a useful source for the regeneration of airway epithelium. Our preliminary study of embryoid body (EB) formation and the air-liquid interface (ALI) method suggested that mouse iPS cells can differentiate into airway epithelial cells. However, whether the cells generated from mouse iPS cells had the character and phenotype of native airway epithelial cells remained uninvestigated. In this study, we generated airway epithelial cells from EBs by culturing them under serum-free conditions supplemented with Activin and bFGF and by the ALI method and characterized the iPS cell-derived airway epithelial cells in terms of their gene expression, immunoreactivity, morphology, and function. Analysis by quantitative real-time reverse transcription-polymerase chain reaction(RT-PCR) revealed that the expression of the undifferentiated cell marker Nanog decreased time-dependently after the induction of differentiation, whereas definitive endoderm markers Foxa2 and Cxcr4 were transiently up-regulated. Thereafter, the expression of airway epithelium markers such as Tubb4a, Muc5ac, and Krt5 was detected by RT-PCR and immunostaining. The formation of tight junctions was also confirmed by immunostaining and permeability assay. Analysis by hematoxylin and eosin staining and scanning electron microscopy indicated that the cells generated from mouse iPS cells formed airway-epithelium-like tissue and had cilia, the movement of which was visualized and observed to be synchronized. These results demonstrate that the airway epithelial cells generated by our method have native characteristics and open new perspectives for the regeneration of injured airway epithelium. PMID:26590823

  11. Sensory neuropeptides and the human lower airways: present state and future directions.

    PubMed

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

    1994-06-01

    The sensory neuropeptides, substance P and neurokinin A, are present in human airway nerves, beneath and within the epithelium, around blood vessels and submucosal glands, and within the bronchial smooth muscle layer. Studies on autopsy tissue, bronchoalveolar lavage and sputum suggest that in asthma the substance P content of the airways may be increased. Neurokinin A is a more potent bronchoconstrictor than substance P. Asthmatics are hyperresponsive to neurokinin A and substance P. The neuropeptide degrading enzyme, neutral endopeptidase is present in the airways and is involved in the degradation of endogenously released and exogenously administered substance P and neurokinin A, both in normal and asthmatic subjects. As for other indirect bronchoconstrictor stimuli, the effect of neurokinin A on airway calibre in asthmatics can be inhibited by pretreatment with nedocromil sodium. Evidence is accumulating, not only from studies in animals but also from experiments on human airways, that tachykinins may also cause mucus secretion and plasma extravasation. They also have important proinflammatory effects, such as the chemoattraction of eosinophils and neutrophils, the adhesion of neutrophils, and the stimulation of lymphocytes, macrophages and mast cells. The tachykinins interact with the targets on the airways by specific tachykinin receptors. The NK1 and the NK2 receptor have been characterized in human airways, both pharmacologically and by cloning. The NK2 receptor is responsible for the in vitro contraction of normal airways, whilst the NK1 receptor is responsible for most of the other airway effects. Because of their presence in the airways and because of their ability to mimic the various pathophysiological features of asthma, substance P and neurokinin A are presently considered as possible mediators of asthma. The present development of potent and selective tachykinin antagonists will allow us to further define the role of tachykinins in the pathogenesis

  12. Airway basal stem cells: a perspective on their roles in epithelial homeostasis and remodeling.

    PubMed

    Rock, Jason R; Randell, Scott H; Hogan, Brigid L M

    2010-01-01

    The small airways of the human lung undergo pathological changes in pulmonary disorders, such as chronic obstructive pulmonary disease (COPD), asthma, bronchiolitis obliterans and cystic fibrosis. These clinical problems impose huge personal and societal healthcare burdens. The changes, termed 'pathological airway remodeling', affect the epithelium, the underlying mesenchyme and the reciprocal trophic interactions that occur between these tissues. Most of the normal human airway is lined by a pseudostratified epithelium of ciliated cells, secretory cells and 6-30% basal cells, the proportion of which varies along the proximal-distal axis. Epithelial abnormalities range from hypoplasia (failure to differentiate) to basal- and goblet-cell hyperplasia, squamous- and goblet-cell metaplasia, dysplasia and malignant transformation. Mesenchymal alterations include thickening of the basal lamina, smooth muscle hyperplasia, fibrosis and inflammatory cell accumulation. Paradoxically, given the prevalence and importance of airway remodeling in lung disease, its etiology is poorly understood. This is due, in part, to a lack of basic knowledge of the mechanisms that regulate the differentiation, maintenance and repair of the airway epithelium. Specifically, little is known about the proliferation and differentiation of basal cells, a multipotent stem cell population of the pseudostratified airway epithelium. This Perspective summarizes what we know, and what we need to know, about airway basal cells to evaluate their contributions to normal and abnormal airway remodeling. We contend that exploiting well-described model systems using both human airway epithelial cells and the pseudostratified epithelium of the genetically tractable mouse trachea will enable crucial discoveries regarding the pathogenesis of airway disease. PMID:20699479

  13. [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

  14. 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

  15. 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

  16. Airway obstruction secondary to large thyroid adenolipoma

    PubMed Central

    Fitzpatrick, Nicholas; Malik, Paras; Hinton-Bayre, Anton; Lewis, Richard

    2014-01-01

    Adenolipoma of the thyroid gland is a rare benign neoplasm composed of normal thyroid and mature adipose tissue. Ordinarily, only a small amount of fat exists in a normal thyroid gland. CT and MRI may differentiate between benign and malignant lesions, and fine-needle aspirate often assists diagnosis. Surgical excision for adenolipoma is considered curative. We report the case of a 67-year-old man presenting with a large neck lump and evidence of airway obstruction. Imaging revealed a 97×70 mm left thyroid mass with retropharyngeal extension and laryngotracheal compression. Hemithyroidectomy was performed with subsequent histology confirming a large thyroid adenolipoma. The patient's symptoms resolved and he remains asymptomatic with no sign of recurrence 2 years postsurgery. PMID:25199190

  17. 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.

  18. 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...

  19. 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

  20. Emergent airway management in a case of fibrodysplasia ossificans progressiva

    PubMed Central

    Parekh, Uma R.; Read, Selina; Desai, Vimal; Budde, Arne O.

    2014-01-01

    Fibrodysplasia ossificans progressiva (FOP), or Stone man syndrome, is rare and one of the most disabling genetic conditions of the connective tissue due to progressive extraskeletal ossification. It usually presents in the first decade of life as painful inflammatory swellings, either spontaneously or in response to trauma, which later ossify and lead to severe disability. Progressive spinal deformity including thoracolumbar kyphoscoliosis leads to thoracic insufficiency syndrome, increasing the risk for pneumonia and right sided heart failure. We present the airway management in a 22-year-old male, diagnosed with FOP with severe disability, who required urgent airway intervention as a result of respiratory failure from pnuemonia. Tracheostomy triggers ossification and consequent airway obstruction at the tracheostomy site and laryngoscopy triggers temporomandibular joint ankylosis. Therefore, awake fiber-optic endotracheal intubation is recommended in these patients. Use of an airway endoscopy mask enabled us to simultaneously maintain non-invasive ventilation and intubate the patient in a situation where tracheostomy needed to be avoided. PMID:25425787

  1. 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

  2. Structural and functional localization of airway effects from episodic exposure of infant monkeys to allergen and/or ozone

    SciTech Connect

    Joad, Jesse P. . E-mail: jesse.joad@ucdmc.ucdavis.edu; Kott, Kayleen S.; Bric, John M.; Peake, Janice L.; Plopper, Charles G.; Schelegle, Edward S.; Gershwin, Laurel J.; Pinkerton, Kent E.

    2006-08-01

    Both allergen and ozone exposure increase asthma symptoms and airway responsiveness in children. Little is known about how these inhalants may differentially modify airway responsiveness in large proximal as compared to small distal airways. We evaluated whether bronchi and respiratory bronchioles from infant monkeys exposed episodically to allergen and/or ozone differentially develop intrinsic hyperresponsiveness to methacholine and whether eosinophils and/or pulmonary neuroendocrine cells play a role. Infant monkeys were exposed episodically for 5 months to: (1) filtered air, (2) aerosolized house dust mite allergen, (3) ozone 0.5 ppm, or (4) house dust mite allergen + ozone. Studying the function/structure relationship of the same lung slices, we evaluated methacholine airway responsiveness and histology of bronchi and respiratory bronchioles. In bronchi, intrinsic responsiveness was increased by allergen exposure, an effect reduced by bombesin antagonist. In respiratory bronchioles, intrinsic airway responsiveness was increased by allergen + ozone exposure. Eosinophils were increased by allergen and allergen + ozone exposure in bronchi and by allergen exposure in respiratory bronchioles. In both airways, exposure to allergen + ozone resulted in fewer tissue eosinophils than did allergen exposure alone. In bronchi, but not in respiratory bronchioles, the number of eosinophils and neuroendocrine cells correlated with airway responsiveness. We conclude that episodically exposing infant monkeys to house dust mite allergen with or without ozone increased intrinsic airway responsiveness to methacholine in bronchi differently than in respiratory bronchioles. In bronchi, eosinophils and neuroendocrine cells may play a role in the development of airway hyperresponsiveness.

  3. 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

  4. S-Nitrosoglutathione Reductase Inhibition Regulates Allergen-Induced Lung Inflammation and Airway Hyperreactivity

    PubMed Central

    Bassett, David J. P.; Bradley, Matthews O.; Jaffar, Zeina

    2013-01-01

    Allergic asthma is characterized by Th2 type inflammation, leading to airway hyperresponsivenes, mucus hypersecretion and tissue remodeling. S-Nitrosoglutathione reductase (GSNOR) is an alcohol dehydrogenase involved in the regulation of intracellular levels of S-nitrosothiols. GSNOR activity has been shown to be elevated in human asthmatic lungs, resulting in diminished S-nitrosothiols and thus contributing to increased airway hyperreactivity. Using a mouse model of allergic airway inflammation, we report that intranasal administration of a new selective inhibitor of GSNOR, SPL-334, caused a marked reduction in airway hyperreactivity, allergen-specific T cells and eosinophil accumulation, and mucus production in the lungs in response to allergen inhalation. Moreover, SPL-334 treatment resulted in a significant decrease in the production of the Th2 cytokines IL-5 and IL-13 and the level of the chemokine CCL11 (eotaxin-1) in the airways. Collectively, these observations reveal that GSNOR inhibitors are effective not only in reducing airway hyperresponsiveness but also in limiting lung inflammatory responses mediated by CD4+ Th2 cells. These findings suggest that the inhibition of GSNOR may provide a novel therapeutic approach for the treatment of allergic airway inflammation. PMID:23936192

  5. 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

  6. 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

  7. Inflammation-induced plasticity of the afferent innervation of the airways.

    PubMed Central

    Carr, M J; Undem, B J

    2001-01-01

    The activation of primary afferent neurons that innervate the airways leads to homeostatic and defensive reflexes. The anatomic and physiologic characteristics of these afferent fibers do not appear to be static properties but rather appear to change rapidly in response to inflammation. The threshold for activation of airway afferent neurons to various stimuli, for example, is not fixed; these fibers can be become sensitized during inflammation. A subset of nociceptive-like (C-fibers) airway afferent neurons not only participates in centrally mediated reflexes but is also thought to release neuropeptides at their peripheral terminals, leading to neurogenic inflammation. An increase in the content of tachykinins is commonly seen in inflamed tissues, and there is accumulating evidence that irritation and inflammation of the airways is associated with the induction of tachykinin synthesis in non-nociceptive airway afferent fibers that under normal conditions do not contain neuropeptides. The release of neurokinins from the peripheral terminals in the airways and their central terminals in the brain stem may contribute to the symptoms of inflammatory airway diseases. Elevated release of neurokinins from peripheral terminals may promote local inflammatory responses, and the release of neurokinins in the brainstem, together with inflammation-induced increases in the excitability of afferent fibers, may culminate in altered visceral autonomic reflex activity, changes in breathing pattern, and cough. PMID:11544165

  8. Circulating progenitor epithelial cells traffic via CXCR4/CXCL12 in response to airway injury.

    PubMed

    Gomperts, Brigitte N; Belperio, John A; Rao, P Nagesh; Randell, Scott H; Fishbein, Michael C; Burdick, Marie D; Strieter, Robert M

    2006-02-01

    Recipient airway epithelial cells are found in human sex-mismatched lung transplants, implying that circulating progenitor epithelial cells contribute to the repair of the airway epithelium. Markers of circulating progenitor epithelial cells and mechanisms for their trafficking remain to be elucidated. We demonstrate that a population of progenitor epithelial cells exists in the bone marrow and the circulation of mice that is positive for the early epithelial marker cytokeratin 5 (CK5) and the chemokine receptor CXCR4. We used a mouse model of sex-mismatched tracheal transplantation and found that CK5+ circulating progenitor epithelial cells contribute to re-epithelialization of the airway and re-establishment of the pseudostratified epithelium. The presence of CXCL12 in tracheal transplants provided a mechanism for CXCR4+ circulating progenitor epithelial cell recruitment to the airway. Depletion of CXCL12 resulted in the epithelium defaulting to squamous metaplasia, which was derived solely from the resident tissue progenitor epithelial cells. Our findings demonstrate that CK5+CXCR4+ cells are markers of circulating progenitor epithelial cells in the bone marrow and circulation and that CXCR4/CXCL12-mediated recruitment of circulating progenitor epithelial cells is necessary for the re-establishment of a normal pseudostratified epithelium after airway injury. These findings support a novel paradigm for the development of squamous metaplasia of the airway epithelium and for developing therapeutic strategies for circulating progenitor epithelial cells in airway diseases. PMID:16424223

  9. Pulmonary surfactant in the airway physiology: a direct relaxing effect on the smooth muscle.

    PubMed

    Calkovska, A; Uhliarova, B; Joskova, M; Franova, S; Kolomaznik, M; Calkovsky, V; Smolarova, S

    2015-04-01

    Beside alveoli, surface active material plays an important role in the airway physiology. In the upper airways it primarily serves in local defense. Lower airway surfactant stabilizes peripheral airways, provides the transport and defense, has barrier and anti-edematous functions, and possesses direct relaxant effect on the smooth muscle. We tested in vitro the effect of two surfactant preparations Curosurf® and Alveofact® on the precontracted smooth muscle of intra- and extra-pulmonary airways. Relaxation was more pronounced for lung tissue strip containing bronchial smooth muscle as the primary site of surfactant effect. The study does not confirm the participation of ATP-dependent potassium channels and cAMP-regulated epithelial chloride channels known as CFTR chloride channels, or nitric oxide involvement in contractile response of smooth muscle to surfactant.By controlling wall thickness and airway diameter, pulmonary surfactant is an important component of airway physiology. Thus, surfactant dysfunction may be included in pathophysiology of asthma, COPD, or other diseases with bronchial obstruction. PMID:25583659

  10. [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

  11. 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

  12. Relationship of small airway chymase-positive mast cells and lung function in severe asthma.

    PubMed

    Balzar, Silvana; Chu, Hong Wei; Strand, Matthew; Wenzel, Sally

    2005-03-01

    Distal lung inflammation may be important in asthma pathophysiology. The goal of this study was to measure cellular inflammation in the large airway and four distal lung regions (small airway inner and outer wall, alveolar attachments, and peripheral alveolar tissue) and to correlate the specific inflammatory cells with several lung function parameters. Sections of concurrently obtained endobronchial and transbronchial/surgical biopsy tissue from 20 individuals with severe asthma were immunostained for T-lymphocyte, eosinophil, monocyte/macrophage, neutrophil, and two mast cell markers (tryptase and chymase). Specific cell distributions were determined and correlated with lung function measures. The number of inflammatory cells generally increased toward the periphery, but the percentage of T-lymphocytes, eosinophils, monocytes/macrophages, and neutrophils remained similar or decreased from large to small airways. In contrast, mast cell number, percentage, and the chymase-positive phenotype increased in small airway regions. After the analysis was adjusted for multiple comparisons, only chymase-positive mast cells significantly and positively correlated with lung function. Such a relationship was seen only in the small airway/alveolar attachments lung region (r(s) = 0.61-0.89; p airway outer wall/alveolar attachments region, may be protective for lung function in severe asthma. PMID:15563633

  13. 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

  14. 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

  15. 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

  16. VAMP8 is a vesicle SNARE that regulates mucin secretion in airway goblet cells.

    PubMed

    Jones, Lisa C; Moussa, Lama; Fulcher, M Leslie; Zhu, Yunxiang; Hudson, Elizabeth J; O'Neal, Wanda K; Randell, Scott H; Lazarowski, Eduardo R; Boucher, Richard C; Kreda, Silvia M

    2012-02-01

    Mucin secretion is an innate defence mechanism, which is noxiously upregulated in obstructive lung diseases (e.g. chronic obstructive pulmonary disease (COPD), cystic fibrosis and asthma). Mucin granule exocytosis is regulated by specific protein complexes, but the SNARE exocytotic core has not been defined in airway goblet cells. In this study, we identify VAMP8 as one of the SNAREs regulating mucin granule exocytosis. VAMP8 mRNA was present in human airway and lung epithelial cells, and deep-sequencing and expression analyses of airway epithelial cells revealed that VAMP8 transcripts were expressed at 10 times higher levels than other VAMP mRNAs. In human airway epithelial cell cultures and freshly excised tissues, VAMP8 immunolocalised mainly to goblet cell mucin granules. The function of VAMP8 in airway mucin secretion was tested by RNA interference techniques. Both VAMP8 short interfering RNAs (siRNAs) and short hairpin RNAs (shRNAs) reduced mucin secretion induced by PAR agonists, neutrophil elastase and ATP in two airway epithelial cell culture models. Notably, basal (non-agonist elicited) mucin secretion was also reduced in these experiments. VAMP8 knockdown was also effective in decreasing mucin secretion in airway epithelial cell cultures with induced mucous metaplasia/mucin hypersecretion. Unlike VAMP8 silencing, knockdown of VAMP2 or VAMP3 did not affect mucin secretion. Importantly, in VAMP8 knock-out (KO) mice with IL-13-induced mucous metaplasia, mucin content in the bronchoalveolar lavage (BAL) and ATP-stimulated mucin secretion in the trachea were reduced compared to WT-matched littermates. Our data indicate that VAMP8 is an essential SNARE in airway mucin granule exocytosis. Reduction of VAMP8 activity/expression may provide a novel therapeutic target to ameliorate airway mucus obstruction in lung diseases. PMID:22144578

  17. Morphologic Characterization of Nerves in Whole-Mount Airway Biopsies

    PubMed Central

    Canning, Brendan J.; Merlo-Pich, Emilio; Woodcock, Ashley A.; Smith, Jaclyn A.

    2015-01-01

    Rationale: Neuroplasticity of bronchopulmonary afferent neurons that respond to mechanical and chemical stimuli may sensitize the cough reflex. Afferent drive in cough is carried by the vagus nerve, and vagal afferent nerve terminals have been well defined in animals. Yet, both unmyelinated C fibers and particularly the morphologically distinct, myelinated, nodose-derived mechanoreceptors described in animals are poorly characterized in humans. To date there are no distinctive molecular markers or detailed morphologies available for human bronchopulmonary afferent nerves. Objectives: Morphologic and neuromolecular characterization of the afferent nerves that are potentially involved in cough in humans. Methods: A whole-mount immunofluorescence approach, rarely used in human lung tissue, was used with antibodies specific to protein gene product 9.5 (PGP9.5) and, for the first time in human lung tissue, 200-kD neurofilament subunit. Measurements and Main Results: We have developed a robust technique to visualize fibers consistent with autonomic and C fibers and pulmonary neuroendocrine cells. A group of morphologically distinct, 200-kD neurofilament-immunopositive myelinated afferent fibers, a subpopulation of which did not express PGP9.5, was also identified. Conclusions: PGP9.5-immunonegative nerves are strikingly similar to myelinated airway afferents, the cough receptor, and smooth muscle–associated airway receptors described in rodents. These have never been described in humans. Full description of human airway nerves is critical to the translation of animal studies to the clinical setting. PMID:25906337

  18. 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

  19. 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

  20. Laryngeal amyloidosis causing hoarseness and airway obstruction.

    PubMed

    Gallivan, Gregory J; Gallivan, Helen K

    2010-03-01

    Amyloidosis constitutes a fraction of 1% of benign localized laryngeal tumors and may occasionally be associated with systemic disease. A chronic, insidious, progressive, recurrent disease characterized by hoarseness, dyspnea, and stridor, it is caused by extracellular deposition of insoluble, abnormal tissue injurious fibrils. Submucosal lesions occur frequently in the vestibular folds and ventricles, less commonly in the subglottis and aryepiglottic folds and least on the vocal folds. Apple green birefrigence under polarized light after Congo red staining, electron microscopic fibrillar structure, and a beta-pleated sheet structure observed by x-ray diffraction are confirmatory. Two presented cases add to the small literature review of similar patients. Case 1 was a 70-year-old man with severe hoarseness, incomplete glottic closure, ovoid concentric stenosis of the inferior glottis and subglottis, who initially was not diagnosed by several laryngologists and speech therapists. He required multiple microlaryngoscopic excisions and dilations. Because low dose radiation induces plasma cell apoptosis in other diseases, external beam radiation therapy (EBRT) was hypothesized to eliminate amyloidogenic plasma cells. Case 2 was a 46-year-old welder with progressive dyspnea for 2-3 years and hoarseness, voice loss, and stridor over 6-7 months. Masses caused airway obstruction of the anterior commissure, vestibular, and vocal folds, with extension to the subglottis. Two phonomicrosurgical CO(2) laser-assisted resections relieved upper airway obstruction and restored voice. Conservative surgical intervention and long-term followup are essential. Further studies are needed to determine if a radiation dose response relationship exists to control laryngeal amyloidosis. PMID:19111441

  1. 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

  2. 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

  3. Role of Matrix Metalloproteinases-1 and -2 in Interleukin-13-Suppressed Elastin in Airway Fibroblasts in Asthma.

    PubMed

    Ingram, Jennifer L; Slade, David; Church, Tony D; Francisco, Dave; Heck, Karissa; Sigmon, R Wesley; Ghio, Michael; Murillo, Anays; Firszt, Rafael; Lugogo, Njira L; Que, Loretta; Sunday, Mary E; Kraft, Monica

    2016-01-01

    Elastin synthesis and degradation in the airway and lung parenchyma contribute to airway mechanics, including airway patency and elastic recoil. IL-13 mediates many features of asthma pathobiology, including airway remodeling, but the effects of IL-13 on elastin architecture in the airway wall are not known. We hypothesized that IL-13 modulates elastin expression in airway fibroblasts from subjects with allergic asthma. Twenty-five subjects with mild asthma (FEV1, 89 ± 3% predicted) and 30 normal control subjects (FEV1, 102 ± 2% predicted) underwent bronchoscopy with endobronchial biopsy. Elastic fibers were visualized in airway biopsy specimens using Weigert's resorcin-fuchsin elastic stain. Airway fibroblasts were exposed to IL-13; a pan-matrix metalloproteinase (MMP) inhibitor (GM6001); specific inhibitors to MMP-1, -2, -3, and -8; and combinations of IL-13 with MMP inhibitors in separate conditions in serum-free media for 48 hours. Elastin (ELN) expression as well as MMP secretion and activity were quantified. Results of this study show that elastic fiber staining of airway biopsy tissue was significantly associated with methacholine PC20 (i.e., the provocative concentration of methacholine resulting in a 20% fall in FEV1 levels) in patients with asthma. IL-13 significantly suppressed ELN expression in asthmatic airway fibroblasts as compared with normal control fibroblasts. The effect of IL-13 on ELN expression was significantly correlated with postbronchodilator FEV1/FVC in patients with asthma. MMP inhibition significantly stimulated ELN expression in patients with asthma as compared with normal control subjects. Specific inhibition of MMP-1 and MMP-2, but not MMP-3 or MMP-8, reversed the IL-13-induced suppression of ELN expression. In asthma, MMP-1 and MMP-2 mediate IL-13-induced suppression of ELN expression in airway fibroblasts. PMID:26074138

  4. 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

  5. Pulmonary C Fibers Modulate MMP-12 Production via PAR2 and Are Involved in the Long-Term Airway Inflammation and Airway Hyperresponsiveness Induced by Respiratory Syncytial Virus Infection

    PubMed Central

    Zang, Na; Zhuang, Jianguo; Deng, Yu; Yang, Zhimei; Ye, Zhixu; Xie, Xiaohong; Ren, Luo; Fu, Zhou; Luo, Zhengxiu; Xu, Fadi

    2015-01-01

    ABSTRACT Children with acute respiratory syncytial virus (RSV) infection often develop sequelae of persistent airway inflammation and wheezing. Pulmonary C fibers (PCFs) are involved in the generation of airway inflammation and resistance; however, their role in persistent airway diseases after RSV is unexplored. Here, we elucidated the pathogenesis of PCF activation in RSV-induced persistent airway disorders. PCF-degenerated and intact mice were used in the current study. Airway inflammation and airway resistance were evaluated. MMP408 and FSLLRY-NH2 were the selective antagonists for MMP-12 and PAR2, respectively, to investigate the roles of MMP-12 and PAR2 in PCFs mediating airway diseases. As a result, PCF degeneration significantly reduced the following responses to RSV infection: augmenting of inflammatory cells, especially macrophages, and infiltrating of inflammatory cells in lung tissues; specific airway resistance (sRaw) response to methacholine; and upregulation of MMP-12 and PAR2 expression. Moreover, the inhibition of MMP-12 reduced the total number of cells and macrophages in bronchiolar lavage fluid (BALF), as well infiltrating inflammatory cells, and decreased the sRaw response to methacholine. In addition, PAR2 was upregulated especially at the later stage of RSV infection. Downregulation of PAR2 ameliorated airway inflammation and resistance following RSV infection and suppressed the level of MMP-12. In all, the results suggest that PCF involvement in long-term airway inflammation and airway hyperresponsiveness occurred at least partially via modulating MMP-12, and the activation of PAR2 might be related to PCF-modulated MMP-12 production. Our initial findings indicated that the inhibition of PCF activity would be targeted therapeutically for virus infection-induced long-term airway disorders. IMPORTANCE The current study is critical to understanding that PCFs are involved in long-term airway inflammation and airway resistance after RSV infection

  6. The Wnt/β-catenin signaling pathway regulates the development of airway remodeling in patients with asthma

    PubMed Central

    Kwak, Hyun Jung; Park, Dong Won; Seo, Ji-Young; Moon, Ji-Yong; Kim, Tae Hyung; Sohn, Jang Won; Shin, Dong Ho; Yoon, Ho Joo; Park, Sung Soo; Kim, Sang-Heon

    2015-01-01

    Airway remodeling is a key characteristic of chronic asthma, particularly in patients with a fixed airflow limitation. The mechanisms underlying airway remodeling are poorly understood, and no therapeutic option is available. The Wnt/β-catenin signaling pathway is involved in various physiological and pathological processes, including fibrosis and smooth muscle hypertrophy. In this study, we investigated the roles of Wnt/β-catenin signaling in airway remodeling in patients with asthma. Wnt7a mRNA expression was prominent in induced sputum from patients with asthma compared with that from healthy controls. Next, we induced a chronic asthma mouse model with airway remodeling features, including subepithelial fibrosis and airway smooth muscle hyperplasia. Higher expression of Wnt family proteins and β-catenin was detected in the lung tissue of mice with chronic asthma compared to control mice. Blocking β-catenin expression with a specific siRNA attenuated airway inflammation and airway remodeling. Decreased subepithelial fibrosis and collagen accumulation in the β-catenin siRNA-treated mice was accompanied by reduced expression of transforming growth factor-β. We further showed that suppressing β-catenin in the chronic asthma model inhibited smooth muscle hyperplasia by downregulating the tenascin C/platelet-derived growth factor receptor pathway. Taken together, these findings demonstrate that the Wnt/β-catenin signaling pathway is highly expressed and regulates the development of airway remodeling in chronic asthma. PMID:26655831

  7. 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

  8. Applying the laser beam for reconstruction of the upper airway

    NASA Astrophysics Data System (ADS)

    Kukwa, Andrzej; Tulibacki, Marek P.; Wojtowicz, Piotr; Dudziec, Katarzyna; Oledzka, Iwona

    2000-11-01

    The authors present their own experience in restoration of the upper airway using a different source of high power laser. There are many patients with a stricture of the upper airway. One of the most common cause insufficiency of this is nosal polyps. Surgical treatment of polyps till now is not sufficiently effective. For this reason we work out a Nd:YAG laser applying technique that let us to reduce a hospitalization time with elongation of an asymptotic period of our patients. Nd:YAG energy we apply for conchoplasty benefiting of its profound coagulation as a distinctive role. This type of laser is very useful in removing of granulation tissue from different areas of the upper airway. Other applications of Nd:YAG laser in our hands is very useful for: coagulation of vessels in Kisselbach area, especially in Rendou-Osler's diseases, resection of the nosal Septo-turbinate adhesions, treatment of hemangiomas and small papillomas in nasal cavity, diminishing of the hypertrophied mucosa in the nasopharyngeal space as well as, reduction of the uvula and soft palate in OSAS patients. In our department we use a Nd:YAG for treatment of precancerous and early stages of cancer and for a palliation procedures in an advanced cancer infiltration in mouth, pharynx and laryngeal region. For treatment removing of cicatrix tissue in a larynx and trachea we use to use a Holm: YAG laser their very superficial penetration of tissues is used for a coagulation of small vessels too let us to resect it without bleeding from a bony and mucosa tissue, as a fragments maxillary sinus wall, nosal septum crest or spine with resection of the posterior pole of a turbinate. Both laser are conveyed by fiberoptic, to reach a pathological changes in many plans, places for this reason we are able to continuously work on a new its applications.

  9. Acute hemorrhagic shock decreases airway resistance in anesthetized rat.

    PubMed

    Bayat, Sam; Albu, Gergely; Layachi, Skander; Portier, Flore; Fathi, Marc; Peták, Ferenc; Habre, Walid

    2011-08-01

    We studied the relation between changes in pulmonary and systemic hemodynamics to those in the airway resistance, respiratory tissue mechanics, and thoracic gas volume (TGV) following acute hemorrhage and blood reinfusion in rats. Forced oscillation technique was used to measure airway resistance (Raw), respiratory tissue damping, and elastance at baseline and after stepwise 1-ml blood withdrawals up to 5 ml total, followed by stepwise reinfusion up to full restoration. Mean systemic (Pam) and pulmonary arterial pressures and suprarenal aortic blood flow were measured at each step. In supplemental animals, plethysmographic TGV, Pam, and respiratory mechanics measurements were performed. Blood volume loss (BVL) led to proportional decreases in Raw (66.5 ± 8.8 vs. 44.8 ± 9.0 cmH(2)O·s·l(-1) with 5 ml, P < 0.001), Pam, and aortic blood flow. In contrast, tissue damping increased significantly (1,070 ± 91 vs. 1,235 ± 105 cmH(2)O/l, P = 0.009 with 5 ml BVL), whereas tissue elastance did not change significantly. TGV significantly increased with acute BVL (3.7 ± 0.2 vs. 4.2 ± 0.2 ml, P = 0.01). Stepwise reinfusions produced opposite changes in the above parameters, with Raw reaching a higher value than baseline (P = 0.001) upon full volume restoration. Both adrenalin (P = 0.015) and noradrenalin levels were elevated (P = 0.010) after 5-ml blood withdrawal. Our data suggest that the decreases in Raw following BVL may be attributed to the following: 1) an increased TGV enhancing airway parenchymal tethering forces; and 2) an increase in circulating catecholamines. The apparent beneficial effect of a reduction in Raw in acute hemorrhagic shock is counteracted by an increase in dead space and the appearance of peripheral mechanical heterogeneities due to de-recruitment of the pulmonary vasculature. PMID:21596916

  10. Airway management in cervical spine injury

    PubMed Central

    Austin, Naola; Krishnamoorthy, Vijay; Dagal, Arman

    2014-01-01

    To minimize risk of spinal cord injury, airway management providers must understand the anatomic and functional relationship between the airway, cervical column, and spinal cord. Patients with known or suspected cervical spine injury may require emergent intubation for airway protection and ventilatory support or elective intubation for surgery with or without rigid neck stabilization (i.e., halo). To provide safe and efficient care in these patients, practitioners must identify high-risk patients, be comfortable with available methods of airway adjuncts, and know how airway maneuvers, neck stabilization, and positioning affect the cervical spine. This review discusses the risks and benefits of various airway management strategies as well as specific concerns that affect patients with known or suspected cervical spine injury. PMID:24741498

  11. 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

  12. Temporal correlation of optical coherence tomography in-vivo images of rabbit airway for the diagnosis of edema

    NASA Astrophysics Data System (ADS)

    Kang, DongYel; Wang, Alex; Tjoa, Tjoson; Volgger, Veronika; Hamamoto, Ashley; Su, Erica; Jing, Joseph; Chen, Zhongping; Wong, Brian J. F.

    2014-03-01

    Recently, full-range optical coherence tomography (OCT) systems have been developed to image the human airway. These novel systems utilize a fiber-based OCT probe which acquires three-dimensional (3-D) images with micrometer resolution. Following an airway injury, mucosal edema is the first step in the body's inflammatory response, which occasionally leads to airway stenosis, a life-threatening condition for critically ill newborns. Therefore, early detection of edema is vital for airway management and prevention of stenosis. In order to examine the potential of the full-range OCT to diagnose edema, we investigated temporal correlation of OCT images obtained from the subglottic airway of live rabbits. Temporally correlated OCT images were acquired at fixed locations in the rabbit subglottis of either artificially induced edema or normal tissues. Edematous tissue was experimentally modeled by injecting saline beneath the epithelial layer of the subglottic mucosa. The calculated cross temporal correlations between OCT images of normal airway regions show periodicity that correlates with the respiratory motion of the airway. However, the temporal correlation functions calculated from OCT images of the edematous regions show randomness without the periodic characteristic. These in-vivo experimental results of temporal correlations between OCT images show the potential of a computer-based or -aided diagnosis of edema in the human respiratory mucosa with a full-range OCT system.

  13. 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

  14. Airway Epithelial Cells are the Site of Expression of a Mammalian Antimicrobial Peptide Gene

    NASA Astrophysics Data System (ADS)

    Diamond, Gill; Jones, Douglas E.; Bevins, Charles L.

    1993-05-01

    We previously reported the isolation and characterization of a broad-spectrum antimicrobial peptide from the bovine tracheal mucosa, which we called tracheal antimicrobial peptide (TAP). We now show the TAP gene is expressed throughout the adult conducting airway, from nasal to bronchiolar tissue, but not in tissues other than airway mucosa, as determined by Northern blot analysis. In situ hybridization of airway sections localizes TAP mRNA to columnar cells of the pseudostratified epithelium. We report the structural organization of the TAP gene and show that TAP is a member of a large family of related sequences with high nucleotide identity in the 5'exon. The data support the hypothesis that antimicrobial peptides contribute to host defense of the respiratory tract.

  15. 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

  16. Emergency bronchoscopy for foreign-body aspiration in a child with type I mucopolysaccharidosis: a challenging airway management experience.

    PubMed

    Kendigelen, Pinar; Tunali, Yusuf; Tutuncu, Ayse; Ashyralyyeva, Gulruh; Emre, Senol; Kaya, Guner

    2016-08-01

    The mucopolysaccharidosis (MPS) is a rare lysosomal storage disease. Glycosaminoglycans (GAG) accumulate in musculoskeletal system, connective tissues. Enlarged tongue, short immobile neck, and limited mobility of the cervical spine and temporomandibular joints render the airway management potentially risky. MPS children have high anesthetic risks, especially in airway management of emergency situations. The foreign-body aspiration requiring intervention with rigid bronchoscopy is an urgent and risky clinical situation. We present our experience with a challenging airway management with a three-year-old child with MPS who needed emergency bronchoscopy due to peanut aspiration. PMID:27146659

  17. Acute regulation of tight junction ion selectivity in human airway epithelia

    PubMed Central

    Flynn, Andrea N.; Itani, Omar A.; Moninger, Thomas O.; Welsh, Michael J.

    2009-01-01

    Electrolyte transport through and between airway epithelial cells controls the quantity and composition of the overlying liquid. Many studies have shown acute regulation of transcellular ion transport in airway epithelia. However, whether ion transport through tight junctions can also be acutely regulated is poorly understood both in airway and other epithelia. To investigate the paracellular pathway, we used primary cultures of differentiated human airway epithelia and assessed expression of claudins, the primary determinants of paracellular permeability, and measured transepithelial electrical properties, ion fluxes, and La3+ movement. Like many other tissues, airway epithelia expressed multiple claudins. Moreover, different cell types in the epithelium expressed the same pattern of claudins. To evaluate tight junction regulation, we examined the response to histamine, an acute regulator of airway function. Histamine stimulated a rapid and transient increase in the paracellular Na+ conductance, with a smaller increase in Cl− conductance. The increase was mediated by histamine H1 receptors and depended on an increase in intracellular Ca2+ concentration. These results suggest that ion flow through the paracellular pathway can be acutely regulated. Such regulation could facilitate coupling of the passive flow of counter ions to active transcellular transport, thereby controlling net transepithelial salt and water transport. PMID:19208806

  18. A differential geometric approach to automated segmentation of human airway tree.

    PubMed

    Pu, Jiantao; Fuhrman, Carl; Good, Walter F; Sciurba, Frank C; Gur, David

    2011-02-01

    Airway diseases are frequently associated with morphological changes that may affect the physiology of the lungs. Accurate characterization of airways may be useful for quantitatively assessing prognosis and for monitoring therapeutic efficacy. The information gained may also provide insight into the underlying mechanisms of various lung diseases. We developed a computerized scheme to automatically segment the 3-D human airway tree depicted on computed tomography (CT) images. The method takes advantage of both principal curvatures and principal directions in differentiating airways from other tissues in geometric space. A "puzzle game" procedure is used to identify false negative regions and reduce false positive regions that do not meet the shape analysis criteria. The negative impact of partial volume effects on small airway detection is partially alleviated by repeating the developed differential geometric analysis on lung anatomical structures modeled at multiple iso-values (thresholds). In addition to having advantages, such as full automation, easy implementation and relative insensitivity to image noise and/or artifacts, this scheme has virtually no leakage issues and can be easily extended to the extraction or the segmentation of other tubular type structures (e.g., vascular tree). The performance of this scheme was assessed quantitatively using 75 chest CT examinations acquired on 45 subjects with different slice thicknesses and using 20 publicly available test cases that were originally designed for evaluating the performance of different airway tree segmentation algorithms. PMID:20851792

  19. Soluble ADAM33 initiates airway remodeling to promote susceptibility for allergic asthma in early life

    PubMed Central

    Davies, Elizabeth R.; Kelly, Joanne F.C.; Howarth, Peter H.; Wilson, David I.; Holgate, Stephen T.; Davies, Donna E.; Whitsett, Jeffrey A.; Haitchi, Hans Michael

    2016-01-01

    Asthma is a chronic inflammatory airways disease that usually begins in early life and involves gene-environment interactions. Although most asthma exhibits allergic inflammation, many allergic individuals do not have asthma. Here, we report how the asthma gene a disintegrin and metalloprotease 33 (ADAM33) acts as local tissue susceptibility gene that promotes allergic asthma. We show that enzymatically active soluble ADAM33 (sADAM33) is increased in asthmatic airways and plays a role in airway remodeling, independent of inflammation. Furthermore, remodeling and inflammation are both suppressed in Adam33-null mice after allergen challenge. When induced in utero or added ex vivo, sADAM33 causes structural remodeling of the airways, which enhances postnatal airway eosinophilia and bronchial hyperresponsiveness following subthreshold challenge with an aeroallergen. This substantial gene-environment interaction helps to explain the end-organ expression of allergic asthma in genetically susceptible individuals. Finally, we show that sADAM33-induced airway remodeling is reversible, highlighting the therapeutic potential of targeting ADAM33 in asthma. PMID:27489884

  20. A Differential Geometric Approach to Automated Segmentation of Human Airway Tree

    PubMed Central

    Pu, Jiantao; Fuhrman, Carl; Good, Walter F; Sciurba, Frank C; Gur, David

    2012-01-01

    Airway diseases are frequently associated with morphological changes that may affect the physiology of the lungs. Accurate characterization of airways may be useful for quantitatively assessing prognosis and for monitoring therapeutic efficacy. The information gained may also provide insight into the underlying mechanisms of various lung diseases. We developed a computerized scheme to automatically segment the three-dimensional human airway tree depicted on CT images. The method takes advantage of both principal curvatures and principal directions in differentiating airways from other tissues in geometric space. A “puzzle game” procedure is used to identify false negative regions and reduce false positive regions that do not meet the shape analysis criteria. The negative impact of partial volume effects on small airway detection is partially alleviated by repeating the developed differential geometric analysis on lung anatomical structures modeled at multiple iso-values (thresholds). In addition to having advantages, such as full automation, easy implementation and relative insensitivity to image noise and/or artifacts, this scheme has virtually no leakage issues and can be easily extended to the extraction or the segmentation of other tubular type structures (e.g., vascular tree). The performance of this scheme was assessed quantitatively using 75 chest CT examinations acquired on 45 subjects with different slice thicknesses and using 20 publicly available test cases that were originally designed for evaluating the performance of different airway tree segmentation algorithms. PMID:20851792

  1. Continuous exposure to house dust mite elicits chronic airway inflammation and structural remodeling.

    PubMed

    Johnson, Jill R; Wiley, Ryan E; Fattouh, Ramzi; Swirski, Filip K; Gajewska, Beata U; Coyle, Anthony J; Gutierrez-Ramos, José-Carlos; Ellis, Russ; Inman, Mark D; Jordana, Manel

    2004-02-01

    It is now fully appreciated that asthma is a disease of a chronic nature resulting from intermittent or continued aeroallergen exposure leading to airway inflammation. To investigate responses to continuous antigen exposure, mice were exposed to either house dust mite extract (HDM) or ovalbumin intranasally for five consecutive days, followed by 2 days of rest, for up to seven consecutive weeks. Continuous exposure to HDM, unlike ovalbumin, elicited severe and persistent eosinophilic airway inflammation. Flow cytometric analysis demonstrated an accumulation of CD4+ lymphocytes in the lung with elevated expression of inducible costimulator a marker of T cell activation, and of T1/ST2, a marker of helper T Type 2 effector cells. We also detected increased and sustained production of helper T cell Type 2-associated cytokines by splenocytes of HDM-exposed mice on in vitro HDM recall. Histologic analysis of the lung showed evidence of airway remodeling in mice exposed to HDM, with goblet cell hyperplasia, collagen deposition, and peribronchial accumulation of contractile tissue. In addition, HDM-exposed mice demonstrated severe airway hyperreactivity to methacholine. Finally, these responses were studied for up to 9 weeks after cessation of HDM exposure. We observed that whereas airway inflammation resolved fully, the remodeling changes did not resolve and airway hyperreactivity resolved only partly. PMID:14597485

  2. Chronic exposure to high levels of particulate air pollution and small airway remodeling.

    PubMed Central

    Churg, Andrew; Brauer, Michael; del Carmen Avila-Casado, Maria; Fortoul, Teresa I; Wright, Joanne L

    2003-01-01

    Recent evidence suggests that chronic exposure to high levels of ambient particulate matter (PM) is associated with decreased pulmonary function and the development of chronic airflow obstruction. To investigate the possible role of PM-induced abnormalities in the small airways in these functional changes, we examined histologic sections from the lungs of 20 women from Mexico City, a high PM locale. All subjects were lifelong residents of Mexico City, were never-smokers, never had occupational dust exposure, and never used biomass fuel for cooking. Twenty never-smoking, non-dust-exposed subjects from Vancouver, British Columbia, Canada, a low PM region, were used as a control. By light microscopy, abnormal small airways with fibrotic walls and excess muscle, many containing visible dust, were present in the Mexico City lungs. Formal grading analysis confirmed the presence of significantly greater amounts of fibrous tissue and muscle in the walls of the airways in the Mexico City compared with the Vancouver lungs. Electron microscopic particle burden measurements on four cases from Mexico City showed that carbonaceous aggregates of ultrafine particles, aggregates likely to be combustion products, were present in the airway mucosa. We conclude that PM penetrates into and is retained in the walls of small airways, and that, even in nonsmokers, long-term exposure to high levels of ambient particulate pollutants is associated with small airway remodeling. This process may produce chronic airflow obstruction. PMID:12727599

  3. [Allergens-induced sensitization alters airway epithelial adhesion molecules expression in mice].

    PubMed

    Zeng, Dan; Tan, Mei-Ling; Xiang, Yang; Qin, Xiao-Qun; Zhu, Li-Ming; Dai, Ai-Guo

    2015-12-25

    To explore the relationship between the epithelial adhesion molecules and immune responses of airway epithelium, we observed the expression of integrin β4 and intercellular adhesion molecule-1 (ICAM-1) in the mice airway epithelium after sensitization with allergens. BALB/c mice were sensitized with intraperitoneal injection of ovalbumin (OVA) or house dust mite (HDM) and then developed airway hyper-responsiveness as determined by barometric whole-body plethysmography. Both OVA and HDM sensitization led to increases of the number of peripheral leukocytes as well as inflammatory cells infiltration in lungs. OVA sensitized mice showed more severe inflammatory cells infiltration than HDM sensitized mice. Immunohistochemistry analysis of mice lung tissues revealed that sensitization with both allergens also led to a decrease of integrin β4 expression and an increase of ICAM-1 expression in airway epithelia. OVA sensitized mice showed a more significant increase of ICAM-1 expression compared with HDM sensitized mice. siRNA mediated silencing of integrin β4 gene in 16HBE cells resulted in an up-regulation of ICAM-1 expression. Our results indicate a possible role of airway epithelial adhesion molecules in allergen-induced airway immune responses. PMID:26701635

  4. A bug's view of allergic airways disease.

    PubMed

    Hsu, Peter S; Campbell, Dianne E

    2016-06-01

    The increase in allergic airways disease has been linked to modern urbanization and lifestyle. Recent evidence suggests that the associated reduction in microbial exposure, reduction in dietary fibre intake and increased antibiotic use may cause early dysbiosis in infancy, which predisposes to immune dysregulation and allergic airways disease later in life. This implies that there may be a window of opportunity for primary prevention strategies aimed to protect or restore the microbiome early in life and thereby decrease the risk of developing allergic airways disease. Alternatively, strategies that correct dysbiosis may aid in the treatment of established allergic airways disease. PMID:27012478

  5. Airway vascular damage in elite swimmers.

    PubMed

    Moreira, André; Palmares, Carmo; Lopes, Cristina; Delgado, Luís

    2011-11-01

    We postulated that high level swimming can promote airway inflammation and thus asthma by enhancing local vascular permeability. We aimed to test this hypothesis by a cross-sectional study comparing swimmers (n = 13, 17 ± 3 years, competing 7 ± 4 years, training 18 ± 3 h per week), asthmatic-swimmers (n = 6, 17 ± 2 years, competing 8 ± 3 years, training 16 ± 4 h per week), and asthmatics (n = 19, 14 ± 3 years). Subjects performed induced sputum and had exhaled nitric oxide, lung volumes, and airway responsiveness determined. Airway vascular permeability index was defined as the ratio of albumin in sputum and serum. Results from the multiple linear regression showed each unit change in airway vascular permeability index was associated with an increase of 0.97% (95%CI: 0.02 to 1.92; p = 0.047) in sputum eosinophilis, and of 2.64% (95%CI:0.96 to 4.31; p = 0.006) in sputum neutrophils after adjustment for confounders. In a general linear model no significant differences between airway vascular permeability between index study groups existed, after controlling for sputum eosinophilis and neutrophils. In conclusion, competitive swimmers training in chlorine-rich pools have similar levels of airway vascular permeability than asthmatics. Although competitive swimming has been associated with asthma, airway inflammation and airway hyperesponsiveness do not seem to be dependent on increased airway vascular permeability. PMID:21669516

  6. 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

  7. Airway sonography in live models and cadavers.

    PubMed

    Tsui, Ban; Ip, Vivian; Walji, Anil

    2013-06-01

    Sonography using cadavers is beneficial in teaching and learning sonoanatomy, which is particularly important because imaging of the airway can be challenging due to the cartilaginous landmarks and air artifacts. In this exploratory study, we have attempted to compare the airway sonoanatomy of cadavers and live models. Our observations support the use of cadavers as teaching tools for learning airway sonoanatomy and practicing procedures involving airway structures, such as superior laryngeal nerve blocks, transtracheal injections, and needle cricothyroidotomy, before performance on patients in clinical situations. We believe this process will improve patient safety and enhance the competency of trainees and practitioners in rare procedures such as needle cricothyroidotomy. PMID:23716527

  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. Physical principle of airway design in human lungs

    NASA Astrophysics Data System (ADS)

    Park, Keunhwan; Son, Taeho; Kim, Wonjung; Kim, Ho-Young

    2014-11-01

    From an engineering perspective, lungs are natural microfluidic devices that extract oxygen from air. In the bronchial tree, airways branch by dichotomy with a systematic reduction of their diameters. It is generally accepted that in conducting airways, which air passes on the way to the acinar airways from the atmosphere, the reduction ratio of diameter is closely related to the minimization of viscous dissipation. Such a principle is formulated as the Hess-Murray law. However, in acinar airways, where oxygen transfer to alveolae occurs, the diameter reduction with progressive generations is more moderate than in conducting airways. Noting that the dominant transfer mechanism in acinar airways is diffusion rather than advection, unlike conducting airways, we construct a mathematical model for oxygen transfer through a series of acinar airways. Our model allows us to predict the optimal airway reduction ratio that maximizes the oxygen transfer in a finite airway volume, thereby rationalizing the observed airway reduction ratio in acinar airways.

  10. A Plasminogen Activator Inhibitor-1 Inhibitor Reduces Airway Remodeling in a Murine Model of Chronic Asthma

    PubMed Central

    Lee, Sun H.; Eren, Mesut; Vaughan, Douglas E.; Schleimer, Robert P.

    2012-01-01

    We previously reported that plasminogen activator inhibitor (PAI)-1 deficiency prevents collagen deposition in the airways of ovalbumin (OVA)-challenged mice. In this study, we explored the therapeutic utility of blocking PAI-1 in preventing airway remodeling, using a specific PAI-1 inhibitor, tiplaxtinin. C57BL/6J mice were immunized with intraperitoneal injections of OVA on Days 0, 3, and 6. Starting on Day 11, mice were challenged with phosphate-buffered saline or OVA by nebulization three times per week for 4 weeks. Tiplaxtinin was mixed with chow and administered orally from 1 day before the phosphate-buffered saline or OVA challenge. Lung tissues were harvested after challenge and characterized histologically for infiltrating inflammatory cells, mucus-secreting goblet cells, and collagen deposition. Airway hyperresponsiveness was measured using whole-body plethysmography. Tiplaxtinin treatment significantly decreased levels of PAI-1 activity in bronchoalveolar lavage fluids, which indicates successful blockage of PAI-1 activity in the airways. The number of infiltrated inflammatory cells was reduced by tiplaxtinin treatment in the lungs of the OVA-challenged mice. Furthermore, oral administration of tiplaxtinin significantly attenuated the degree of goblet cell hyperplasia and collagen deposition in the airways of the OVA-challenged mice, and methacholine-induced airway hyperresponsiveness was effectively reduced by tiplaxtinin in these animals. This study supports our previous findings that PAI-1 promotes airway remodeling in a murine model of chronic asthma, and suggests that PAI-1 may be a novel target of treatment of airway remodeling in asthma. PMID:22323366

  11. A plasminogen activator inhibitor-1 inhibitor reduces airway remodeling in a murine model of chronic asthma.

    PubMed

    Lee, Sun H; Eren, Mesut; Vaughan, Douglas E; Schleimer, Robert P; Cho, Seong H

    2012-06-01

    We previously reported that plasminogen activator inhibitor (PAI)-1 deficiency prevents collagen deposition in the airways of ovalbumin (OVA)-challenged mice. In this study, we explored the therapeutic utility of blocking PAI-1 in preventing airway remodeling, using a specific PAI-1 inhibitor, tiplaxtinin. C57BL/6J mice were immunized with intraperitoneal injections of OVA on Days 0, 3, and 6. Starting on Day 11, mice were challenged with phosphate-buffered saline or OVA by nebulization three times per week for 4 weeks. Tiplaxtinin was mixed with chow and administered orally from 1 day before the phosphate-buffered saline or OVA challenge. Lung tissues were harvested after challenge and characterized histologically for infiltrating inflammatory cells, mucus-secreting goblet cells, and collagen deposition. Airway hyperresponsiveness was measured using whole-body plethysmography. Tiplaxtinin treatment significantly decreased levels of PAI-1 activity in bronchoalveolar lavage fluids, which indicates successful blockage of PAI-1 activity in the airways. The number of infiltrated inflammatory cells was reduced by tiplaxtinin treatment in the lungs of the OVA-challenged mice. Furthermore, oral administration of tiplaxtinin significantly attenuated the degree of goblet cell hyperplasia and collagen deposition in the airways of the OVA-challenged mice, and methacholine-induced airway hyperresponsiveness was effectively reduced by tiplaxtinin in these animals. This study supports our previous findings that PAI-1 promotes airway remodeling in a murine model of chronic asthma, and suggests that PAI-1 may be a novel target of treatment of airway remodeling in asthma. PMID:22323366

  12. JNK-TLR9 signal pathway mediates allergic airway inflammation through suppressing melatonin biosynthesis.

    PubMed

    Wu, Hui-Mei; Shen, Qi-Ying; Fang, Lei; Zhang, Shi-Hai; Shen, Pei-Ting; Liu, Ya-Jing; Liu, Rong-Yu

    2016-05-01

    Toll-like receptors (TLRs) play pivotal role in the pathogenesis of allergic airway diseases such as asthma. TLR9 is one of the most extensively studied TLRs as an approach to treat asthma. In this study, we investigated the role of TLR9 in the allergic airway inflammation and the underlying mechanism. Wild-type (WT) mice and TLR9(-/-) mice were sensitized and challenged with OVA to establish allergic airway disease model. We found that the expression of TLR9 was elevated concomitantly with airway inflammation post-OVA challenge, and TLR9 deficiency effectively inhibited airway inflammation, including serum OVA-specific immunoglobulin E (IgE), pulmonary inflammatory cell recruitment, mucus secretion, and bronchoalveolar lavage fluid (BALF) inflammatory cytokine production. Meanwhile, the protein expression of hydroxyindole-o-methyltransferase (HIOMT) in lung tissues, the level of melatonin in serum, and BALF were reduced in OVA-challenged WT mice, while these reductions were significantly restored by TLR9 deficiency. Additionally, we showed that although TLR9 deficiency had no effect on OVA-induced phosphorylation of JNK, inhibition of JNK by specific inhibitor SP600125 significantly decreased OVA-induced expression of TLR9, suggesting that JNK is the upstream signal molecular of TLR9. Furthermore, SP600125 treatment promoted resolution of allergic airway inflammation in OVA-challenged WT mice, but not further ameliorated allergic airway inflammation in OVA-challenged TLR9(-/-) mice. Similarly, SP600125 significantly restored the protein expression of HIOMT and the level of melatonin in OVA-challenged WT mice, while such effect was not further enhanced by TLR9 deficiency. Collectively, our results indicated that JNK-TLR9 signal pathway mediates allergic airway inflammation through suppressing melatonin biosynthesis. PMID:26914888

  13. The role of mast cells in citric acid-induced airway constriction and cough.

    PubMed

    Lai, Yih-Loong; Wu, Li-Ling; Lin, Tai-Yin; Lin, Chien-He

    2009-11-30

    Inhalation of citric acid (CA) causes airway constriction and coughing. To investigate the role of mast cells in CA-induced airway constriction and cough, three experiments using guinea pigs were carried out. In the first experiment, we used compound 48/80 to deplete mast cells, cromolyn sodium to stabilize mast cells, MK-886 to inhibit synthesis of leukotrienes, pyrilamine to antagonize histamine H1 receptor, methysergide to antagonize serotonin receptor, and indomethacin to inhibit cyclooxygenase. In the second experiment, compound 48/80-pretreated animals were divided into 2 parts; the first one was used to test the role of exogenous leukotriene (LT) C4, while the second one to test the role of exogenous histamine. Decreases in respiratory compliance (Crs) and forced expiratory volume in 0.1 sec (FEV0.1) were used as indicators for airway constriction in anesthetized guinea pigs. CA-induced cough was recorded for 12 min using a barometric body plethysmograph in conscious animals. In the third experiment, the activation of mast cells upon CA inhalation was investigated by determining lung tissue or arterial plasma histamine concentration in animals. Exposure to CA induced marked airway constriction and increase in cough number. Compound 48/80, cromolyn sodium, MK-886 and pyrilamine, but not indomethacin or methysergide, significantly attenuated CA-induced airway constriction and cough. Injection of LTC4 or histamine caused a significant increase in CA-induced airway constriction and cough in compound 48/80-pretreated animals. In addition, CA inhalation caused significant increase in lung tissue and plasma histamine concentrations, which were blocked by compound 48/80 pretreatment. These results suggest that mast cells play an important role in CA aerosol inhalation-induced airway constriction and cough via perhaps mediators including LTs and histamine. PMID:20359123

  14. Neutrophilic oxidative stress mediates organic dust-induced pulmonary inflammation and airway hyperresponsiveness.

    PubMed

    McGovern, Toby K; Chen, Michael; Allard, Benoit; Larsson, Kjell; Martin, James G; Adner, Mikael

    2016-01-15

    Airway exposure to organic dust (OD) from swine confinement facilities induces airway inflammation dominated by neutrophils and airway hyperresponsiveness (AHR). One important neutrophilic innate defense mechanism is the induction of oxidative stress. Therefore, we hypothesized that neutrophils exacerbate airway dysfunction following OD exposure by increasing oxidant burden. BALB/C mice were given intranasal challenges with OD or PBS (1/day for 3 days). Mice were untreated or treated with a neutrophil-depleting antibody, anti-Ly6G, or the antioxidant dimethylthiourea (DMTU) prior to OD exposure. Twenty-four hours after the final exposure, we measured airway responsiveness in response to methacholine (MCh) and collected bronchoalveolar lavage fluid to assess pulmonary inflammation and total antioxidant capacity. Lung tissue was harvested to examine the effect of OD-induced antioxidant gene expression and the effect of anti-Ly6G or DMTU. OD exposure induced a dose-dependent increase of airway responsiveness, a neutrophilic pulmonary inflammation, and secretion of keratinocyte cytokine. Depletion of neutrophils reduced OD-induced AHR. DMTU prevented pulmonary inflammation involving macrophages and neutrophils. Neutrophil depletion and DMTU were highly effective in preventing OD-induced AHR affecting large, conducting airways and tissue elastance. OD induced an increase in total antioxidant capacity and mRNA levels of NRF-2-dependent antioxidant genes, effects that are prevented by administration of DMTU and neutrophil depletion. We conclude that an increase in oxidative stress and neutrophilia is critical in the induction of OD-induced AHR. Prevention of oxidative stress diminishes neutrophil influx and AHR, suggesting that mechanisms driving OD-induced AHR may be dependent on neutrophil-mediated oxidant pathways. PMID:26545900

  15. Patterns of airway involvement in inflammatory bowel diseases

    PubMed Central

    Papanikolaou, Ilias; Kagouridis, Konstantinos; Papiris, Spyros A

    2014-01-01

    Extraintestinal manifestations occur commonly in inflammatory bowel diseases (IBD). Pulmonary manifestations (PM) of IBD may be divided in airway disorders, interstitial lung disorders, serositis, pulmonary vasculitis, necrobiotic nodules, drug-induced lung disease, thromboembolic lung disease and enteropulmonary fistulas. Pulmonary involvement may often be asymptomatic and detected solely on the basis of abnormal screening tests. The common embryonic origin of the intestine and the lungs from the primitive foregut, the co-existence of mucosa associated lymphoid tissue in both organs, autoimmunity, smoking and bacterial translocation from the colon to the lungs may all be involved in the pathogenesis of PM in IBD. PM are mainly detected by pulmonary function tests and high-resolution computed tomography. This review will focus on the involvement of the airways in the context of IBD, especially stenoses of the large airways, tracheobronchitis, bronchiectasis, bronchitis, mucoid impaction, bronchial granulomas, bronchiolitis, bronchiolitis obliterans syndrome and the co-existence of IBD with asthma, chronic obstructive pulmonary disease, sarcoidosis and a1-antitrypsin deficiency. PMID:25400999

  16. Palliative treatment of malignant stenoses of the lower airways with the FIBERTOM Nd:YAG laser

    NASA Astrophysics Data System (ADS)

    Pirozynski, Michal; Polubiec-Kownacka, Malgorzata; Strojecki, Krzysztof; Blachnio, Antoni; Pawlak, Wieslaw; Krusiewicz, Jan

    1996-03-01

    Neodymium yttrium aluminum garnet (Nd:YAG) laser, with its infrared wavelength of 1064 nm, is at present the most useful modality in treatment of lower airways obstruction of the lower airways by malignant and benign lesions. In fact that was the first indication for a successful restoration of a narrowed airway by Toty et al. The therapeutical effects of this laser are based on thermal action. The exposed tissue undergoes a progressive transformation by a localized increase in the temperature from warming, protein coagulation, to evaporation of water and vaporization of the tissue. This study represents the initial experience with the use of the FIBERTOMTM Nd:YAG laser in removal of obstructing malignant and non- malignant lesions of the lower airways. Twenty-six patients (mean age 55.7 plus or minus 17.4 years) were included in the study. The main indications for laser therapy were in 16 patients exophytic cancerous lesions of the trachea and main bronchi, benign tumors of the major airways in 6, and in 4 cancerous lesions of the lobar bronchi. Squamous cell lung cancer and adenocarcinoma were diagnosed most often. The degree of obstruction ranged from 70% to 99%. Complete recanalization was achieved in 19 of the 26 patients, in only one patient recanalization was not achieved. The major complication was fever -- seen in 17 (65.4%) patients and cough (19.2%). Long term observation identified 18 patients alive after 52 weeks following laser therapy.

  17. Obliterative airway remodeling: molecular evidence for shared pathways in transplanted and native lungs.

    PubMed

    Jonigk, Danny; Merk, Marlene; Hussein, Kais; Maegel, Lavinia; Theophile, Katharina; Muth, Michaela; Lehmann, Ulrich; Bockmeyer, Clemens L; Mengel, Michael; Gottlieb, Jens; Welte, Tobias; Haverich, Axel; Golpon, Heiko; Kreipe, Hans; Laenger, Florian

    2011-02-01

    Obliteration of the small airways is a largely unresolved challenge in pulmonary medicine. It represents either the irreversible cause of functional impairment or a morphologic disorder of limited importance in a multitude of diseases. Bronchiolitis obliterans is a key complication of lung transplantation. No predictive markers for the onset of obliterative remodeling are currently available. To further elucidate the molecular mechanisms of airway remodeling, compartment-specific expression patterns were analyzed in patients. For this purpose, remodeled and nonremodeled bronchioli were isolated from transplanted and nontransplanted lung explants using laser-assisted microdissection (n = 24). mRNA expression of 45 fibrosis-associated genes was measured using quantitative real-time RT-PCR. For 20 genes, protein expression was also analyzed by immunohistochemistry. Infiltrating cells were characterized at conventional histology and immunohistochemistry. Obliterative remodeling of the small airways in transplanted and nontransplanted lungs shared similar grades of chronic inflammation and pivotal fibrotic pathways such as transforming growth factor β signaling and increased collagen expression. Bone morphogenetic protein and thrombospondin signaling, and also matrix metalloproteinases and tissue inhibitor of metalloproteinases, were primarily up-regulated in obliterative airway remodeling in nontransplanted lungs. In transplanted lungs, clinical remodeled bone morphogenetic protein but nonremodeled bronchioli were characterized by a concordant up-regulation of matrix metalloproteinase-9, RANTES, and tissue inhibitor of metalloproteinase-1. These distinct expression patterns warrant further investigation as potential markers of impending airway remodeling, especially for prospective longitudinal molecular profiling. PMID:21281792

  18. Congenital pulmonary airway malformation: A report of two cases

    PubMed Central

    Bolde, Saroj; Pudale, Smita; Pandit, Gopal; Ruikar, Kirti; Ingle, Sachin B

    2015-01-01

    Congenital pulmonary airway malformation (CPAM), previously known as congenital cystic adenomatoid malformation is a congenital disorder of the lung similar to bronchopulmonary sequestration. In CPAM, usually an entire lobe of lung is replaced by a non-working cystic piece of abnormal lung tissue. This abnormal tissue will never function as normal lung tissue. The underlying cause for CPAM is not known. It occurs in approximately 1 in every 30000 pregnancies. The association between CPAM and malignancy has been well documented. There is a small risk (0.7%) of malignant transformation within the cyst. So early diagnosis and surgical resection is important to prevent the grave complications. Herein, we are reporting two interesting cases of CPAM and one belonged to Type II and other belonged to Type III of Stocker’s classification. PMID:25984523

  19. Role of EP2 and EP4 receptors in airway microvascular leak induced by prostaglandin E2

    PubMed Central

    Jones, Victoria C; Birrell, Mark A; Maher, Sarah A; Griffiths, Mark; Grace, Megan; O'Donnell, Valerie B; Clark, Stephen R

    2016-01-01

    Background and Purpose Airway microvascular leak (MVL) involves the extravasation of proteins from post‐capillary venules into surrounding tissue. MVL is a cardinal sign of inflammation and an important feature of airway inflammatory diseases such as asthma. PGE2, a product of COX‐mediated metabolism of arachidonic acid, binds to four receptors, termed EP1–4. PGE2 has a wide variety of effects within the airway, including modulation of inflammation, sensory nerve activation and airway tone. However, the effect of PGE2 on airway MVL and the receptor/s that mediate this have not been described. Experimental Approach Evans Blue dye was used as a marker of airway MVL, and selective EP receptor agonists and antagonists were used alongside EP receptor‐deficient mice to define the receptor subtype involved. Key Results PGE2 induced significant airway MVL in mice and guinea pigs. A significant reduction in PGE2‐induced MVL was demonstrated in Ptger2 −/− and Ptger4 −/− mice and in wild‐type mice pretreated simultaneously with EP2 (PF‐04418948) and EP4 (ER‐819762) receptor antagonists. In a model of allergic asthma, an increase in airway levels of PGE2 was associated with a rise in MVL; this change was absent in Ptger2 −/− and Ptger4 −/− mice. Conclusions and Implications PGE2 is a key mediator produced by the lung and has widespread effects according to the EP receptor activated. Airway MVL represents a response to injury and under ‘disease’ conditions is a prominent feature of airway inflammation. The data presented highlight a key role for EP2 and EP4 receptors in MVL induced by PGE2. PMID:26639895

  20. Effects of tracheal airway occlusion on hyoid muscle length and upper airway volume.

    PubMed

    van Lunteren, E; Haxhiu, M A; Cherniack, N S

    1989-12-01

    Complex relationships exist among electromyograms (EMGs) of the upper airway muscles, respective changes in muscle length, and upper airway volume. To test the effects of preventing lung inflation on these relationships, recordings were made of EMGs and length changes of the geniohyoid (GH) and sternohyoid (SH) muscles as well as of tidal changes in upper airway volume in eight anesthetized cats. During resting breathing, tracheal airway occlusion tended to increase the inspiratory lengthening of GH and SH. In response to progressive hypercapnia, the GH eventually shortened during inspiration in all animals; the extent of muscle shortening was minimally augmented by airway occlusion despite substantial increases in EMGs. SH lengthened during inspiration in six of eight animals under hypercapnic conditions, and in these cats lengthening was greater during airway occlusion even though EMGs increased. Despite the above effects on SH and GH length, upper airway tidal volume was increased significantly by tracheal occlusion under hypercapnic conditions. These data suggest that the thoracic and upper airway muscle reflex effects of preventing lung inflation during inspiration act antagonistically on hyoid muscle length, but, because of the mechanical arrangement of the hyoid muscles relative to the airway and thorax, they act agonistically to augment tidal changes in upper airway volume. The augmentation of upper airway tidal volume may occur in part as a result of the effects of thoracic movements being passively transmitted through the hyoid muscles. PMID:2606835

  1. Acid aspiration-induced airways hyperresponsiveness in mice.

    PubMed

    Allen, Gilman B; Leclair, Timothy R; von Reyn, Jessica; Larrabee, Yuna C; Cloutier, Mary E; Irvin, Charles G; Bates, Jason H T

    2009-12-01

    The role of gastroesophageal reflux and micro-aspiration as a trigger of airways hyperresponsiveness (AHR) in patients with asthma is controversial. The role of acid reflux and aspiration as a direct cause of AHR in normal subjects is also unclear. We speculated that aspiration of a weak acid with a pH (1.8) equivalent to the upper range of typical gastric contents would lead to AHR in naive mice. We further speculated that modest reductions in aspirate acidity to a level expected during gastric acid suppression therapy (pH 4.0) would impede aspiration-induced AHR. BALB/c female mice were briefly anesthetized with isoflurane and allowed to aspirate 75 microl of saline with HCl (pH 1.8, 4.0, or 7.4) or underwent sham aspiration. Mice were re-anesthetized 2 or 24 h later, underwent tracheostomy, and were coupled to a mechanical ventilator. Forced oscillations were used to periodically measure respiratory impedance (Zrs) following aerosol delivery of saline and increasing doses of methacholine to measure for AHR. Values for elastance (H), airways resistance (R(N)), and tissue damping (G) were derived from Zrs. Aspirate pH of 1.8 led to a significant overall increase in peak R(N), G, and H compared with pH 4.0 and 7.4 at 2 and 24 h. Differences between pH 7.4 and 4.0 were not significant. In mice aspirating pH 1.8 compared with controls, airway lavage fluid contained more neutrophils, higher protein, and demonstrated higher permeability. We conclude that acid aspiration triggers an acute AHR, driven principally by breakdown of epithelial barrier integrity within the airways. PMID:19797689

  2. Acid aspiration-induced airways hyperresponsiveness in mice

    PubMed Central

    Leclair, Timothy R.; von Reyn, Jessica; Larrabee, Yuna C.; Cloutier, Mary E.; Irvin, Charles G.; Bates, Jason H. T.

    2009-01-01

    The role of gastroesophageal reflux and micro-aspiration as a trigger of airways hyperresponsiveness (AHR) in patients with asthma is controversial. The role of acid reflux and aspiration as a direct cause of AHR in normal subjects is also unclear. We speculated that aspiration of a weak acid with a pH (1.8) equivalent to the upper range of typical gastric contents would lead to AHR in naive mice. We further speculated that modest reductions in aspirate acidity to a level expected during gastric acid suppression therapy (pH 4.0) would impede aspiration-induced AHR. BALB/c female mice were briefly anesthetized with isoflurane and allowed to aspirate 75 μl of saline with HCl (pH 1.8, 4.0, or 7.4) or underwent sham aspiration. Mice were re-anesthetized 2 or 24 h later, underwent tracheostomy, and were coupled to a mechanical ventilator. Forced oscillations were used to periodically measure respiratory impedance (Zrs) following aerosol delivery of saline and increasing doses of methacholine to measure for AHR. Values for elastance (H), airways resistance (RN), and tissue damping (G) were derived from Zrs. Aspirate pH of 1.8 led to a significant overall increase in peak RN, G, and H compared with pH 4.0 and 7.4 at 2 and 24 h. Differences between pH 7.4 and 4.0 were not significant. In mice aspirating pH 1.8 compared with controls, airway lavage fluid contained more neutrophils, higher protein, and demonstrated higher permeability. We conclude that acid aspiration triggers an acute AHR, driven principally by breakdown of epithelial barrier integrity within the airways. PMID:19797689

  3. Characterization of side population cells from human airway epithelium.

    PubMed

    Hackett, Tillie-Louise; Shaheen, Furquan; Johnson, Andrew; Wadsworth, Samuel; Pechkovsky, Dmitri V; Jacoby, David B; Kicic, Anthony; Stick, Stephen M; Knight, Darryl A

    2008-10-01

    The airway epithelium is the first line of contact with the inhaled external environment and is continuously exposed to and injured by pollutants, allergens, and viruses. However, little is known about epithelial repair and in particular the identity and role of tissue resident stem/progenitor cells that may contribute to epithelial regeneration. The aims of the present study were to identify, isolate, and characterize side population (SP) cells in human tracheobronchial epithelium. Epithelial cells were obtained from seven nontransplantable healthy lungs and four asthmatic lungs by pronase digestion. SP cells were identified by verapamil-sensitive efflux of the DNA-binding dye Hoechst 33342. Using flow cytometry, CD45(-) SP, CD45(+) SP, and non-SP cells were isolated and sorted. CD45(-) SP cells made up 0.12% +/- 0.01% of the total epithelial cell population in normal airway but 4.1% +/- 0.06% of the epithelium in asthmatic airways. All CD45(-) SP cells showed positive staining for epithelial-specific markers cytokeratin-5, E-cadherin, ZO-1, and p63. CD45(-) SP cells exhibited stable telomere length and increased colony-forming and proliferative potential, undergoing population expansion for at least 16 consecutive passages. In contrast with non-SP cells, fewer than 100 CD45(-) SP cells were able to generate a multilayered and differentiated epithelium in air-liquid interface culture. SP cells are present in human tracheobronchial epithelium, exhibit both short- and long-term proliferative potential, and are capable of generation of differentiated epithelium in vitro. The number of SP cells is significantly greater in asthmatic airways, providing evidence of dysregulated resident SP cells in the asthmatic epithelium. Disclosure of potential conflicts of interest is found at the end of this article. PMID:18653771

  4. Classification of vibratory patterns of the upper airway during sleep.

    PubMed

    Alshaer, Hisham; Rudzicz, Frank; Falk, Tiago H; Tseng, Wen-Hou; Bradley, T Douglas

    2013-01-01

    Upper airway (UA) narrowing and collapse during sleep results in obstructive sleep apnea (OSA). We hypothesize that vibratory patterns of snoring can distinguish simple snorers from those with OSA. Samples of breath sounds were collected from 7 snorers without OSA and 5 with OSA. Snoring pitch (F0) contours were found using the robust algorithm for pitch tracking (RAPT). The OSA snoring contours showed fluctuating patterns as compared to the smoother patterns of simple snorers. This suggests that snoring reveals the underlying instabilities of UA tissue in OSA. Conditional random fields, a statistical sequence classifier, gave 75% accuracy in distinguishing the 2 groups. PMID:24110129

  5. Athletic Trainers' Knowledge Regarding Airway Adjuncts

    ERIC Educational Resources Information Center

    Edler, Jessica R.; Eberman, Lindsey E.; Kahanov, Leamor; Roman, Christopher; Mata, Heather Lynne

    2015-01-01

    Context: Research suggests that knowledge gaps regarding the appropriate use of airway adjuncts exist among various health care practitioners, and that knowledge is especially limited within athletic training. Objective: To determine the relationship between perceived knowledge (PK) and actual knowledge (AK) of airway adjunct use and the…

  6. SUBCHRONIC ENDOTOXIN INHALATION CAUSES PERSISTENT AIRWAY DISEASE

    EPA Science Inventory

    ABSTRACT

    The endotoxin component of organic dusts causes acute reversible airflow obstruction and airway inflammation. To test the hypothesis that endotoxin alone causes airway remodeling, we have compared the response of two inbred mouse strains to subchronic endotoxin ...

  7. 21 CFR 868.5100 - Nasopharyngeal airway.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Nasopharyngeal airway. 868.5100 Section 868.5100 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5100 Nasopharyngeal airway....

  8. 21 CFR 868.5110 - Oropharyngeal airway.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Oropharyngeal airway. 868.5110 Section 868.5110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5110 Oropharyngeal airway....

  9. 21 CFR 868.5100 - Nasopharyngeal airway.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Nasopharyngeal airway. 868.5100 Section 868.5100 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5100 Nasopharyngeal airway....

  10. 21 CFR 868.5110 - Oropharyngeal airway.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Oropharyngeal airway. 868.5110 Section 868.5110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5110 Oropharyngeal airway....

  11. 21 CFR 868.5100 - Nasopharyngeal airway.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Nasopharyngeal airway. 868.5100 Section 868.5100 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5100 Nasopharyngeal airway....

  12. 21 CFR 868.5100 - Nasopharyngeal airway.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Nasopharyngeal airway. 868.5100 Section 868.5100 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5100 Nasopharyngeal airway....

  13. 21 CFR 868.5110 - Oropharyngeal airway.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Oropharyngeal airway. 868.5110 Section 868.5110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5110 Oropharyngeal airway....

  14. 21 CFR 868.5100 - Nasopharyngeal airway.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Nasopharyngeal airway. 868.5100 Section 868.5100 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5100 Nasopharyngeal airway....

  15. 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

  16. 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

  17. Regulation of human airway surface liquid.

    PubMed

    Widdicombe, J H; Widdicombe, J G

    1995-01-01

    Human airways are lined with a film of liquid from 5-100 microns in depth, consisting of a periciliary sol around and a mucous gel above the cilia. Microscopical studies have shown the sol to be invariably the same depth as the length of the cilia, and we discuss possible reasons for this. The composition and sources of the airway surface liquid are also described. In addition the forces regulating its volume are analyzed. Several airway diseases are characterised by dramatic changes in the volume and composition of airway liquid. We review recent research suggesting that the accumulation of airway mucous secretions in cystic fibrosis is caused by alterations in active transport of ions and water across both the surface and gland epithelia. PMID:7740210

  18. Awake Craniotomy: A New Airway Approach.

    PubMed

    Sivasankar, Chitra; Schlichter, Rolf A; Baranov, Dimitry; Kofke, W Andrew

    2016-02-01

    Awake craniotomies have been performed regularly at the University of Pennsylvania since 2004. Varying approaches to airway management are described for this procedure, including intubation with an endotracheal tube and use of a laryngeal mask airway, simple facemask, or nasal cannula. In this case series, we describe the successful use (i.e., no need for endotracheal intubation related to inadequate gas exchange) of bilateral nasopharyngeal airways in 90 patients undergoing awake craniotomies. The use of nasopharyngeal airways can ease the transition between the asleep and awake phases of the craniotomy without the need to stimulate the airway. Our purpose was to describe our experience and report adverse events related to this technique. PMID:26579845

  19. Airway fires during surgery: Management and prevention

    PubMed Central

    Akhtar, Navaid; Ansar, Farrukh; Baig, Mirza Shahzad; Abbas, Akbar

    2016-01-01

    Airway fires pose a serious risk to surgical patients. Fires during surgery have been reported for many years with flammable anesthetic agents being the main culprits in the past. Association of airway fires with laser surgery is well-recognized, but there are reports of endotracheal tube fires ignited by electrocautery during pharyngeal surgery or tracheostomy or both. This uncommon complication has potentially grave consequences. While airway fires are relatively uncommon occurrences, they are very serious and can often be fatal. Success in preventing such events requires a thorough understanding of the components leading to a fire (fuel, oxidizer, and ignition source), as well as good communication between all members present to appropriately manage the fire and ensure patient safety. We present a case of fire in the airway during routine adenotonsillectomy. We will review the causes, preventive measures, and brief management for airway fires. PMID:27006554

  20. 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

  1. 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

  2. Immunomodulation of airway epithelium cell activation by mesenchymal stromal cells ameliorates house dust mite-induced airway inflammation in mice.

    PubMed

    Duong, Khang M; Arikkatt, Jaisy; Ullah, M Ashik; Lynch, Jason P; Zhang, Vivian; Atkinson, Kerry; Sly, Peter D; Phipps, Simon

    2015-11-01

    Allergic asthma is underpinned by T helper 2 (Th2) inflammation. Redundancy in Th2 cytokine function and production by innate and adaptive immune cells suggests that strategies aimed at immunomodulation may prove more beneficial. Hence, we sought to determine whether administration of mesenchymal stromal cells (MSCs) to house dust mite (HDM) (Dermatophagoides pteronyssinus)-sensitized mice would suppress the development of Th2 inflammation and airway hyperresponsiveness (AHR) after HDM challenge. We report that the intravenous administration of allogeneic donor MSCs 1 hour before allergen challenge significantly attenuated the features of allergic asthma, including tissue eosinophilia, Th2 cytokine (IL-5 and IL-13) levels in bronchoalveolar lavage fluid, and AHR. The number of infiltrating type 2 innate lymphoid cells was not affected by MSC transfer, suggesting that MSCs may modulate the adaptive arm of Th2 immunity. The effect of MSC administration was long lasting; all features of allergic airway disease were significantly suppressed in response to a second round of HDM challenge 4 weeks after MSC administration. Further, we observed that MSCs decreased the release of epithelial cell-derived alarmins IL-1α and high mobility group box-1 in an IL-1 receptor antagonist-dependent manner. This significantly decreased the expression of the pro-Th2 cytokine IL-25 and reduced the number of activated and antigen-acquiring CD11c(+)CD11b(+) dendritic cells in the lung and mediastinal lymph nodes. Our findings suggest that MSC administration can ameliorate allergic airway inflammation by blunting the amplification of epithelial-derived inflammatory cytokines induced by HDM exposure and may offer long-term protection against Th2-mediated allergic airway inflammation and AHR. PMID:25789608

  3. Investigating the geometry of pig airways using computed tomography

    NASA Astrophysics Data System (ADS)

    Mansy, Hansen A.; Azad, Md Khurshidul; McMurray, Brandon; Henry, Brian; Royston, Thomas J.; Sandler, Richard H.

    2015-03-01

    Numerical modeling of sound propagation in the airways requires accurate knowledge of the airway geometry. These models are often validated using human and animal experiments. While many studies documented the geometric details of the human airways, information about the geometry of pig airways is scarcer. In addition, the morphology of animal airways can be significantly different from that of humans. The objective of this study is to measure the airway diameter, length and bifurcation angles in domestic pigs using computed tomography. After imaging the lungs of 3 pigs, segmentation software tools were used to extract the geometry of the airway lumen. The airway dimensions were then measured from the resulting 3 D models for the first 10 airway generations. Results showed that the size and morphology of the airways of different animals were similar. The measured airway dimensions were compared with those of the human airways. While the trachea diameter was found to be comparable to the adult human, the diameter, length and branching angles of other airways were noticeably different from that of humans. For example, pigs consistently had an early airway branching from the trachea that feeds the superior (top) right lung lobe proximal to the carina. This branch is absent in the human airways. These results suggested that the human geometry may not be a good approximation of the pig airways and may contribute to increasing the errors when the human airway geometric values are used in computational models of the pig chest.

  4. Puberty and Upper Airway Dynamics During Sleep

    PubMed Central

    Bandla, Preetam; Huang, Jingtao; Karamessinis, Laurie; Kelly, Andrea; Pepe, Michelle; Samuel, John; Brooks, Lee; Mason, Thornton. A.; Gallagher, Paul R.; Marcus, Carole L.

    2008-01-01

    Study Objectives: The upper airway compensatory response to subatmospheric pressure loading declines with age. The epidemiology of obstructive sleep apnea suggests that sex hormones play a role in modulating upper airway function. Sex hormones increase gradually during puberty, from minimally detectable to adult levels. We hypothesized that the upper airway response to subatmospheric pressure loading decreased with increasing pubertal Tanner stage in males but remained stable during puberty in females. Design: Upper airway dynamic function during sleep was measured over the course of puberty. Participants: Normal subjects of Tanner stages 1 to 5. Measurements: During sleep, maximal inspiratory airflow was measured while varying the level of nasal pressure. The slope of the upstream pressure-flow relationship (SPF) was measured. Results: The SPF correlated with age and Tanner stage. However, the relationship with Tanner stage became nonsignificant when the correlation due to the mutual association with age was removed. Females had a lower SPF than males. Conclusions: In both sexes, the upper airway compensatory response to subatmospheric pressure loading decreased with age rather than degree of pubertal development. Thus, changes in sex hormones are unlikely to be a primary modulator of upper airway function during the transition from childhood to adulthood. Although further studies of upper airway structural changes during puberty are needed, we speculate that the changes in upper airway function with age are due to the depressant effect of age on ventilatory drive, leading to a decrease in upper airway neuromotor tone. Citation: Bandla P; Huang J; Karamessinis L; Kelly A; Pepe M; Samuel J; Brooks L; Mason TA; Gallagher PR; Marcus CL. Puberty and Upper Airway Dynamics During Sleep. SLEEP 2008;31(4):534-541. PMID:18457241

  5. Single-stage surgical repair of airway gastric fistula after esophagectomy

    PubMed Central

    2014-01-01

    Airway gastric fistula (AGF) is a rare but catastrophic complication after esophagectomy. Surgical repair with viable tissue interposed between the airway and alimentary tracts remains the definitive treatment. However, it is challenging for surgeons, and only anecdotally described in sporadic case reports due to the complexity of the techniques necessary for successful surgical intervention. Here, we report two cases successfully managed via single-stage surgical re-exploration. On outpatient follow-up, the two Chinese patients were progressing satisfactorily without complaint of any dyspnea or dysphagia. PMID:24506968

  6. Computational Fluid Dynamic Analysis of the Posterior Airway Space After Maxillomandibular Advancement For Obstructive Sleep Apnea Syndrome

    PubMed Central

    Sittitavornwong, Somsak; Waite, Peter D.; Shih, Alan M.; Cheng, Gary C.; Koomullil, Roy; Ito, Yasushi; Cure, Joel K; Harding, Susan M.; Litaker, Mark

    2013-01-01

    Purpose Evaluate the soft tissue change of the upper airway after maxillomandibular advancement (MMA) by computational fluid dynamics (CFD). Materials and Methods Eight OSAS patients who required MMA were recruited into this study. All participants had pre- and post-operative computed tomography (CT) and underwent MMA by a single oral and maxillofacial surgeon. Upper airway CT data sets for these 8 participants were created with high-fidelity 3-D numerical models for computational fluid dynamics (CFD). The 3-D models were simulated and analyzed to study how changes in airway anatomy affects pressure effort required for normal breathing. Airway dimensions, skeletal changes, Apnea-Hypopnea Index (AHI), and pressure efforts of pre- and post-operative 3-D models were compared and correlations interpreted. Results After MMA, laminar and turbulent air flow was significantly decreased at every level of the airway. The cross-sectional areas at the soft palate and tongue base were significantly increased. Conclusions This study shows that MMA increases airway dimensions by the increasing the occipital base (Base) - pogonion (Pg) distance. An increase of the Base-Pg distance showed a significant correlation with an AHI improvement and a decreased pressure effort of the upper airway. Decreasing the pressure effort will decrease the breathing workload. This improves the condition of OSAS. PMID:23642544

  7. Allergic airways disease develops after an increase in allergen capture and processing in the airway mucosa.

    PubMed

    von Garnier, Christophe; Wikstrom, Matthew E; Zosky, Graeme; Turner, Debra J; Sly, Peter D; Smith, Miranda; Thomas, Jennifer A; Judd, Samantha R; Strickland, Deborah H; Holt, Patrick G; Stumbles, Philip A

    2007-11-01

    Airway mucosal dendritic cells (AMDC) and other airway APCs continuously sample inhaled Ags and regulate the nature of any resulting T cell-mediated immune response. Although immunity develops to harmful pathogens, tolerance arises to nonpathogenic Ags in healthy individuals. This homeostasis is thought to be disrupted in allergic respiratory disorders such as allergic asthma, such that a potentially damaging Th2-biased, CD4(+) T cell-mediated inflammatory response develops against intrinsically nonpathogenic allergens. Using a mouse model of experimental allergic airways disease (EAAD), we have investigated the functional changes occurring in AMDC and other airway APC populations during disease onset. Onset of EAAD was characterized by early and transient activation of airway CD4(+) T cells coinciding with up-regulation of CD40 expression exclusively on CD11b(-) AMDC. Concurrent enhanced allergen uptake and processing occurred within all airway APC populations, including B cells, macrophages, and both CD11b(+) and CD11b(-) AMDC subsets. Immune serum transfer into naive animals recapitulated the enhanced allergen uptake observed in airway APC populations and mediated activation of naive allergen-specific, airway CD4(+) T cells following inhaled allergen challenge. These data suggest that the onset of EAAD is initiated by enhanced allergen capture and processing by a number of airway APC populations and that allergen-specific Igs play a role in the conversion of normally quiescent AMDC subsets into those capable of inducing airway CD4(+) T cell activation. PMID:17947647

  8. Investigating in vivo airway wall mechanics during tidal breathing with optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Robertson, Claire; Lee, Sang-Won; Ahn, Yeh-Chan; Mahon, Sari; Chen, Zhongping; Brenner, Matthew; George, Steven C.

    2011-10-01

    Optical coherence tomography (OCT) is a nondestructive imaging technique offering high temporal and spatial resolution, which makes it a natural choice for assessing tissue mechanical properties. We have developed methods to mechanically analyze the compliance of the rabbit trachea in vivo using tissue deformations induced by tidal breathing, offering a unique tool to assess the behavior of the airways during their normal function. Four-hundred images were acquired during tidal breathing with a custom-built endoscopic OCT system. The surface of the tissue was extracted from a set of these images via image processing algorithms, filtered with a bandpass filter set at respiration frequency to remove cardiac and probe motion, and compared to ventilatory pressure to calculate wall compliance. These algorithms were tested on elastic phantoms to establish reliability and reproducibility. The mean tracheal wall compliance (in five animals) was 1.3+/-0.3×10-5 (mm Pa)-1. Unlike previous work evaluating airway mechanics, this new method is applicable in vivo, noncontact, and loads the trachea in a physiological manner. The technique may have applications in assessing airway mechanics in diseases such as asthma that are characterized by significant airway remodeling.

  9. Vaccination against IL-33 Inhibits Airway Hyperresponsiveness and Inflammation in a House Dust Mite Model of Asthma

    PubMed Central

    Lei, Ying; Adner, Mikael; Hellman, Lars; Nilsson, Gunnar

    2015-01-01

    In several clinical and experimental studies IL-33 and its receptor have been found to play important roles in the development of asthma and allergic airway inflammation. We evaluated the effects of vaccination against IL-33 in a mouse model of airway inflammation induced by house dust mite (HDM) allergen. Balb/c mice received the IL-33 vaccine subcutaneously, followed by intranasal administration of HDM for up to six weeks. Vaccination against IL-33 induced high titers of specific anti-IL-33 IgG antibodies that inhibited HDM-induced airway hyperresponsiveness (AHR) in the conducting airways and tissue damping. The vaccination also attenuated the HDM-induced elevation in the numbers of eosinophils in bronchoalveolar lavage fluid (BALF) and suppressed the accumulation of inflammatory cells in the airways. Furthermore, the levels of IL-17A, IL-25, IL-33 and TSLP in lung tissue homogenates were reduced by vaccination against IL-33. These observations demonstrate that vaccination against IL-33 inhibits HDM-induced development of AHR, airway inflammation and production of inflammatory cytokines. The results also indicate an important role of IL-33 in the regulation of AHR of the distal lung compartments. Thus, administration of such a vaccine is potentially an effective therapeutic tool for treating allergic asthma. PMID:26214807

  10. Rapid nongenomic actions of inhaled corticosteroids on long-acting β(2)-agonist transport in the airway.

    PubMed

    Horvath, Gabor; Mendes, Eliana S; Schmid, Nathalie; Schmid, Andreas; Conner, Gregory E; Fregien, Nevis L; Salathe, Matthias; Wanner, Adam

    2011-12-01

    Corticosteroids inhibit organic cation transporters (OCTs) that play an important role in drug absorption, tissue distribution and elimination. Corticosteroid sensitivity of bronchodilator trafficking in the airway tissue, however, is poorly understood. To assess the effects of inhaled corticosteroids on airway absorption and disposal mechanisms of long-acting β(2)-agonists, human airway epithelial and smooth muscle cell uptake of tritiated formoterol and salmeterol was measured in vitro. Corticosteroids caused a rapid, concentration-dependent inhibition of uptake of the cationic formoterol by airway smooth muscle cells, but not airway epithelial cells. Uptake of the non-charged lipophilic salmeterol was corticosteroid-insensitive in both cell types. In smooth muscle cells, inhaled corticosteroids inhibited formoterol uptake with a novel potency rank order: des-ciclesonide > budesonide > beclomethasone 17-monopropionate > beclomethasone dipropionate > ciclesonide > fluticasone. The inhibitory action was rapidly reversible, and was not enhanced by prolonged corticosteroid exposure or sensitive to a transcription inhibitor. Suppression of OCT3 expression using lentivirus-mediated production of shRNA reduced corticosteroid sensitivity of formoterol uptake by smooth muscle cells. Our data support a corticosteroid insensitive absorption and a corticosteroid-sensitive disposition mechanism for cationic long-acting β(2)-agonist bronchodilators in the airway. Potency rank order and other 'classical' features of anti-inflammatory effects do not apply to inhaled corticosteroids' rapid drug transport actions. PMID:21914487

  11. Educating the Educator: Teaching Airway Adjunct Techniques in Athletic Training

    ERIC Educational Resources Information Center

    Berry, David C.; Seitz, S. Robert

    2011-01-01

    The 5th edition of the "Athletic Training Education Competencies" ("Competencies") now requires athletic training educators (ATEs) to introduce into the curriculum various types of airway adjuncts including: (1) oropharyngeal airways (OPA), (2) nasopharyngeal airways (NPA), (3) supraglottic airways (SGA), and (4) suction. The addition of these…

  12. Small particles disrupt postnatal airway development

    PubMed Central

    Lee, DongYoub; Wallis, Chris; Schelegle, Edward S.; Van Winkle, Laura S.; Plopper, Charles G.; Fanucchi, Michelle V.; Kumfer, Ben; Kennedy, Ian M.; Chan, Jackie K. W.

    2010-01-01

    Increasing numbers of epidemiologic studies associate air pollution exposure in children with decreased lung function development. The objective of this study was to examine the effects of exposure to combustion-generated fine [230 and 212 nm number mean aerodynamic particle diameter (NMAD)] to ultrafine (73 nm NMAD) particles differing in elemental (EC) and organic (OC) carbon content on postnatal airway development in rats. Neonatal Sprague-Dawley rats were exposed from postnatal day 7 through 25, and lung function and airway architecture were evaluated 81 days of age. In a separate group of rats, cell proliferation was examined after a single particle exposure at 7 days of age. Early life exposure to 73 nm high OC/EC particles altered distal airway architecture and resulted in subtle changes in lung mechanics. Early life exposure to 212 nm high OC/EC particles did not alter lung architecture but did alter lung mechanics in a manner suggestive of central airway changes. In contrast, early life exposure to 230 nm low OC/EC particles did not alter lung architecture or mechanics. A single 6-h exposure to 73 nm high OC/EC particle decreased airway cell proliferation, whereas 212 nm high OC/EC particles increased it and 230 nm low OC/EC particles did not. The early life exposure to ultrafine, high OC/EC particles results in persistent alterations in distal airway architecture that is characterized by an initial decrease in airway cell proliferation. PMID:20634362

  13. 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

  14. 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.

  15. Breath tests and airway gas exchange.

    PubMed

    Anderson, Joseph C; Hlastala, Michael P

    2007-01-01

    Measuring soluble gas in the exhaled breath is a non-invasive technique used to estimate levels of respiratory, solvent, and metabolic gases. The interpretation of these measurements is based on the assumption that the measured gases exchange in the alveoli. While the respiratory gases have a low blood-solubility and exchange in the alveoli, high blood-soluble gases exchange in the airways. The effect of airway gas exchange on the interpretation of these exhaled breath measurements can be significant. We describe airway gas exchange in relation to exhaled measurements of soluble gases that exchange in the alveoli. The mechanisms of airway gas exchange are reviewed and criteria for determining if a gas exchanges in the airways are provided. The effects of diffusion, perfusion, temperature and breathing maneuver on airway gas exchange and on measurement of exhaled soluble gas are discussed. A method for estimating the impact of airway gas exchange on exhaled breath measurements is presented. We recommend that investigators should carefully control the inspired air conditions and type of exhalation maneuver used in a breath test. Additionally, care should be taken when interpreting breath tests from subjects with pulmonary disease. PMID:16413216

  16. Human airway musculature on a chip: an in vitro model of allergic asthmatic bronchoconstriction and bronchodilation.

    PubMed

    Nesmith, Alexander Peyton; Agarwal, Ashutosh; McCain, Megan Laura; Parker, Kevin Kit

    2014-10-21

    Many potential new asthma therapies that show promise in the pre-clinical stage of drug development do not demonstrate efficacy during clinical trials. One factor contributing to this problem is the lack of human-relevant models of the airway that recapitulate the tissue-level structural and functional phenotypes of asthma. Hence, we sought to build a model of a human airway musculature on a chip that simulates healthy and asthmatic bronchoconstriction and bronchodilation in vitro by engineering anisotropic, laminar bronchial smooth muscle tissue on elastomeric thin films. In response to a cholinergic agonist, the muscle layer contracts and induces thin film bending, which serves as an in vitro analogue for bronchoconstriction. To mimic asthmatic inflammation, we exposed the engineered tissues to interleukin-13, which resulted in hypercontractility and altered relaxation in response to cholinergic challenge, similar to responses observed clinically in asthmatic patients as well as in studies with animal tissue. Moreover, we reversed asthmatic hypercontraction using a muscarinic antagonist and a β-agonist which are used clinically to relax constricted airways. Importantly, we demonstrated that targeting RhoA-mediated contraction using HA1077 decreased basal tone, prevented hypercontraction, and improved relaxation of the engineered tissues exposed to IL-13. These data suggest that we can recapitulate the structural and functional hallmarks of human asthmatic musculature on a chip, including responses to drug treatments for evaluation of safety and efficacy of new drugs. Further, our airway musculature on a chip provides an important tool for enabling mechanism-based search for new therapeutic targets through the ability to evaluate engineered muscle at the levels of protein expression, tissue structure, and tissue function. PMID:25093641

  17. Effect of dexamethasone and ACC on bacteria-induced mucin expression in human airway mucosa.

    PubMed

    Hauber, Hans-Peter; Goldmann, Torsten; Vollmer, Ekkehard; Wollenberg, Barbara; Zabel, Peter

    2007-11-01

    Gram-negative bacteria can stimulate mucin production, but excessive mucus supports bacterial infection and consequently leads to airway obstruction. Therefore, the effect of dexamethasone (DEX) and the antioxidant acetyl-cysteine (ACC) on bacteria-induced mucus expression was investigated. Explanted human airway mucosa and mucoepidermoid cells (Calu-3) were stimulated with lipopolysaccharide (LPS) or PAM3 (a synthetic lipoprotein). DEX or ACC were added to either LPS- or PAM3-stimulated airway mucosa or Calu-3 cells. Mucin mRNA expression (MUC5AC) and total mucus glycoconjugates (mucin protein) were quantified using real-time PCR and periodic acid Schiff staining. LPS and PAM3 significantly increased mucin expression in airway mucosa and Calu-3 cells (P < 0.05). DEX alone had no significant effect on mucin expression in airway mucosa or Calu-3 cells (P > 0.05). In contrast, DEX significantly reduced LPS- and PAM3-induced mucin expression in explanted mucosal tissue and mucin expression in Calu-3 cells (P < 0.05). In explanted human airway mucosa ACC alone significantly increased mucin expression (P < 0.05). In contrast, ACC significantly decreased LPS- and PAM3-induced mucin expression (P < 0.05). In Calu-3 cells ACC alone had no significant effect on mucin expression (P > 0.05). ACC decreased LPS- and PAM3-induced mucin expression, but this effect was not significant (P > 0.05). These data suggest that DEX can effectively reduce bacteria-induced mucin expression in the airways. ACC alone may increase mucin expression in noninfected mucosa, but it decreased bacteria-induced mucin expression. Further studies are warranted to evaluate whether the effect of DEX or ACC is clinically relevant. PMID:17600317

  18. Automated segmentation of lung airway wall area measurements from bronchoscopic optical coherence tomography imaging

    NASA Astrophysics Data System (ADS)

    Heydarian, Mohammadreza; Choy, Stephen; Wheatley, Andrew; McCormack, David; Coxson, Harvey O.; Lam, Stephen; Parraga, Grace

    2011-03-01

    Chronic Obstructive Pulmonary Disease (COPD) affects almost 600 million people and is currently the fourth leading cause of death worldwide. COPD is an umbrella term for respiratory symptoms that accompany destruction of the lung parenchyma and/or remodeling of the airway wall, the sum of which result in decreased expiratory flow, dyspnea and gas trapping. Currently, x-ray computed tomography (CT) is the main clinical method used for COPD imaging, providing excellent spatial resolution for quantitative tissue measurements although dose limitations and the fundamental spatial resolution of CT limit the measurement of airway dimensions beyond the 5th generation. To address this limitation, we are piloting the use of bronchoscopic Optical Coherence Tomography (OCT), by exploiting its superior spatial resolution of 5-15 micrometers for in vivo airway imaging. Currently, only manual segmentation of OCT airway lumen and wall have been reported but manual methods are time consuming and prone to observer variability. To expand the utility of bronchoscopic OCT, automatic and robust measurement methods are required. Therefore, our objective was to develop a fully automated method for segmenting OCT airway wall dimensions and here we explore several different methods of image-regeneration, voxel clustering and post-processing. Our resultant automated method used K-means or Fuzzy c-means to cluster pixel intensity and then a series of algorithms (i.e. cluster selection, artifact removal, de-noising) was applied to process the clustering results and segment airway wall dimensions. This approach provides a way to automatically and rapidly segment and reproducibly measure airway lumen and wall area.

  19. Interleukin-22 exacerbates airway inflammation induced by short-term exposure to cigarette smoke in mice

    PubMed Central

    Li, Jiu-rong; Zhou, Wei-xun; Huang, Ke-wu; Jin, Yang; Gao, Jin-ming

    2014-01-01

    Aim: Interleukin-22 (IL-22) exhibits both proinflammatory and anti-inflammatory properties in various biological processes. In this study we explored the effects of exogenous recombinant IL-22 (rIL-22) on cigarette smoke (CS)-induced airway inflammation in mice. Methods: Male C57BL/6 mice were divided into groups: (1) CS group exposed to tobacco smoke for 3 consecutive days, (2) rIL-22 group received rIL-22 (100 mg/kg, ip), and (3) CS plus rIL-22 group, received rIL-22 (100 mg/kg, ip) before the CS exposure. The airway resistance (Rn), lung morphology, inflammatory cells in the airways, and inflammatory cytokines and CXCR3 ligands in both bronchoalveolar lavage (BAL) fluids and lung tissues were analyzed. Results: CS alone significantly elevated IL-22 level in the BAL fluid. Both CS and rIL-22 significantly augmented airway resistance, an influx of inflammatory cells into the airways and lung parenchyma, and significantly elevated levels of pro-inflammatory cytokines (TGFβ1 and IL-17A) and CXCR3 chemokines (particularly CXCL10) at the mRNA and/or protein levels. Furthermore, the effects of rIL-22 on airway resistance and inflammation were synergistic with those of CS, as demonstrated by a further increased Rn value, infiltration of greater numbers of inflammatory cells into the lung, higher levels of inflammatory cytokines and chemokines, and more severe pathological changes in CS plus rIL-22 group as compared to those in CS group. Conclusion: Exogenous rIL-22 exacerbates the airway inflammatory responses to CS exposure in part by inducing expression of several proinflammatory cytokines and CXCR3 ligands. PMID:25345745

  20. In Utero Cigarette Smoke Affects Allergic Airway Disease But Does Not Alter the Lung Methylome.

    PubMed

    Eyring, Kenneth R; Pedersen, Brent S; Yang, Ivana V; Schwartz, David A

    2015-01-01

    Prenatal and postnatal cigarette smoke exposure enhances the risk of developing asthma. Despite this as well as other smoking related risks, 11% of women still smoke during pregnancy. We hypothesized that cigarette smoke exposure during prenatal development generates long lasting differential methylation altering transcriptional activity that correlates with disease. In a house dust mite (HDM) model of allergic airway disease, we measured airway hyperresponsiveness (AHR) and airway inflammation between mice exposed prenatally to cigarette smoke (CS) or filtered air (FA). DNA methylation and gene expression were then measured in lung tissue. We demonstrate that HDM-treated CS mice develop a more severe allergic airway disease compared to HDM-treated FA mice including increased AHR and airway inflammation. While DNA methylation changes between the two HDM-treated groups failed to reach genome-wide significance, 99 DMRs had an uncorrected p-value < 0.001. 6 of these 99 DMRs were selected for validation, based on the immune function of adjacent genes, and only 2 of the 6 DMRs confirmed the bisulfite sequencing data. Additionally, genes near these 6 DMRs (Lif, Il27ra, Tle4, Ptk7, Nfatc2, and Runx3) are differentially expressed between HDM-treated CS mice and HDM-treated FA mice. Our findings confirm that prenatal exposure to cigarette smoke is sufficient to modify allergic airway disease; however, it is unlikely that specific methylation changes account for the exposure-response relationship. These findings highlight the important role in utero cigarette smoke exposure plays in the development of allergic airway disease. PMID:26642056

  1. In Utero Cigarette Smoke Affects Allergic Airway Disease But Does Not Alter the Lung Methylome

    PubMed Central

    Eyring, Kenneth R.; Pedersen, Brent S.; Yang, Ivana V.; Schwartz, David A.

    2015-01-01

    Prenatal and postnatal cigarette smoke exposure enhances the risk of developing asthma. Despite this as well as other smoking related risks, 11% of women still smoke during pregnancy. We hypothesized that cigarette smoke exposure during prenatal development generates long lasting differential methylation altering transcriptional activity that correlates with disease. In a house dust mite (HDM) model of allergic airway disease, we measured airway hyperresponsiveness (AHR) and airway inflammation between mice exposed prenatally to cigarette smoke (CS) or filtered air (FA). DNA methylation and gene expression were then measured in lung tissue. We demonstrate that HDM-treated CS mice develop a more severe allergic airway disease compared to HDM-treated FA mice including increased AHR and airway inflammation. While DNA methylation changes between the two HDM-treated groups failed to reach genome-wide significance, 99 DMRs had an uncorrected p-value < 0.001. 6 of these 99 DMRs were selected for validation, based on the immune function of adjacent genes, and only 2 of the 6 DMRs confirmed the bisulfite sequencing data. Additionally, genes near these 6 DMRs (Lif, Il27ra, Tle4, Ptk7, Nfatc2, and Runx3) are differentially expressed between HDM-treated CS mice and HDM-treated FA mice. Our findings confirm that prenatal exposure to cigarette smoke is sufficient to modify allergic airway disease; however, it is unlikely that specific methylation changes account for the exposure-response relationship. These findings highlight the important role in utero cigarette smoke exposure plays in the development of allergic airway disease. PMID:26642056

  2. Loss of anion transport without increased sodium absorption characterizes newborn porcine cystic fibrosis airway epithelia.

    PubMed

    Chen, Jeng-Haur; Stoltz, David A; Karp, Philip H; Ernst, Sarah E; Pezzulo, Alejandro A; Moninger, Thomas O; Rector, Michael V; Reznikov, Leah R; Launspach, Janice L; Chaloner, Kathryn; Zabner, Joseph; Welsh, Michael J

    2010-12-10

    Defective transepithelial electrolyte transport is thought to initiate cystic fibrosis (CF) lung disease. Yet, how loss of CFTR affects electrolyte transport remains uncertain. CFTR⁻(/)⁻ pigs spontaneously develop lung disease resembling human CF. At birth, their airways exhibit a bacterial host defense defect, but are not inflamed. Therefore, we studied ion transport in newborn nasal and tracheal/bronchial epithelia in tissues, cultures, and in vivo. CFTR⁻(/)⁻ epithelia showed markedly reduced Cl⁻ and HCO₃⁻ transport. However, in contrast to a widely held view, lack of CFTR did not increase transepithelial Na(+) or liquid absorption or reduce periciliary liquid depth. Like human CF, CFTR⁻(/)⁻ pigs showed increased amiloride-sensitive voltage and current, but lack of apical Cl⁻ conductance caused the change, not increased Na(+) transport. These results indicate that CFTR provides the predominant transcellular pathway for Cl⁻ and HCO₃⁻ in porcine airway epithelia, and reduced anion permeability may initiate CF airway disease. PMID:21145458

  3. Acute unilateral submandibular gland swelling associated with the laryngeal mask airway.

    PubMed

    Suhitharan, Thangavelautham; Seevanayagam, Sathyendran; Parker, Francis Christopher; Teoh, Wendy Hui Ling

    2013-12-01

    We describe a rare complication of acute unilateral submandibular gland swelling following the use of laryngeal mask airway (LMA) in two patients with otherwise uneventful perioperative airway management. This is likely to be a consequence of the pressure exerted by the airway cuff on the tissues within the submandibular triangle. As this complication is rarely reported, its true incidence may in fact be higher, suggesting a need for greater attention on LMA cuff pressures and degree of cuff inflation. We discuss the presenting clinical features, pathophysiology and utilisation of ultrasonographic confirmation of sialadenopathy, and review the current anaesthetic literature to raise awareness of this unusual and under-reported complication of LMA. This complication can be mitigated by incorporating routine manometric checks and limiting intracuff pressures to < 60 cmH2O, potentially avoiding LMA insertions in patients with sialolithiasis and avoiding the use of nitrous oxide. PMID:24356762

  4. Control of regulatory T cells and airway tolerance by lung macrophages and dendritic cells.

    PubMed

    Duan, Wei; Croft, Michael

    2014-12-01

    Airway tolerance, a state of immunological surveillance, suppresses the development of lung inflammatory disorders that are driven by various pathological effector cells of the immune system. Tolerance in the lung to inhaled antigens is primarily mediated by regulatory T cells (Treg cells) that can inhibit effector T cells via a myriad of mechanisms. Accumulating evidence suggests that regulatory antigen-presenting cells are critical for generating Treg cells and/or maintaining the suppressive environment in the lung. This review focuses on the control of airway tolerance by Treg cells and the role of regulatory lung tissue and alveolar macrophages, and lung and lymph node dendritic cells, in contributing to airway tolerance that is associated with suppression of allergic asthmatic disease. PMID:25525738

  5. Injury induces direct lineage segregation of functionally distinct airway basal stem/progenitor cell subpopulations.

    PubMed

    Pardo-Saganta, Ana; Law, Brandon M; Tata, Purushothama Rao; Villoria, Jorge; Saez, Borja; Mou, Hongmei; Zhao, Rui; Rajagopal, Jayaraj

    2015-02-01

    Following injury, stem cells restore normal tissue architecture by producing the proper number and proportions of differentiated cells. Current models of airway epithelial regeneration propose that distinct cytokeratin 8-expressing progenitor cells, arising from p63(+) basal stem cells, subsequently differentiate into secretory and ciliated cell lineages. We now show that immediately following injury, discrete subpopulations of p63(+) airway basal stem/progenitor cells themselves express Notch pathway components associated with either secretory or ciliated cell fate commitment. One basal cell population displays intracellular Notch2 activation and directly generates secretory cells; the other expresses c-myb and directly yields ciliated cells. Furthermore, disrupting Notch ligand activity within the basal cell population at large disrupts the normal pattern of lineage segregation. These non-cell-autonomous effects demonstrate that effective airway epithelial regeneration requires intercellular communication within the broader basal stem/progenitor cell population. These findings have broad implications for understanding epithelial regeneration and stem cell heterogeneity. PMID:25658372

  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. Airways disorders and the swimming pool.

    PubMed

    Bougault, Valérie; Boulet, Louis-Philippe

    2013-08-01

    Concerns have been expressed about the possible detrimental effects of chlorine derivatives in indoor swimming pool environments. Indeed, a controversy has arisen regarding the possibility that chlorine commonly used worldwide as a disinfectant favors the development of asthma and allergic diseases. The effects of swimming in indoor chlorinated pools on the airways in recreational and elite swimmers are presented. Recent studies on the influence of swimming on airway inflammation and remodeling in competitive swimmers, and the phenotypic characteristics of asthma in this population are reviewed. Preventative measures that could potentially reduce the untoward effects of pool environment on airways of swimmers are discussed. PMID:23830132

  8. Brachycephalic airway syndrome: pathophysiology and diagnosis.

    PubMed

    Lodato, Dena L; Hedlund, Cheryl S

    2012-07-01

    Brachycephalic airway syndrome (BAS) is a group of abnormalities that result in upper airway obstruction. Primary malformations include stenotic nares, elongated soft palate, and hypoplastic trachea, which cause an increase in negative pressure within the upper airways that can eventually lead to secondary abnormalities such as everted laryngeal saccules, everted tonsils, and laryngeal and tracheal collapse. Abnormal nasopharyngeal turbinates are also encountered, but have not been classified as primary or secondary. BAS is readily diagnosed, and quality of life is improved with appropriate medical and/or surgical management. PMID:22847322

  9. Airway nitric oxide in microgravity

    NASA Astrophysics Data System (ADS)

    Linnarsson, D.; Gustafsson, L.; Hemmingsson, Tryggve; Frostell, C.; Paiva, M.

    2005-10-01

    Nitric Oxide (NO), a molecule with a wide range of biological effects, is found in exhaled gas. Elevation of expired NO is an early sign of airway inflammation in asthma and dust inhalation. Animal experiments have demonstrated a marked increase of expired NO after venous gas emboli (bubbles, VGE), which may occur after decompression in conjunction with extravehicular activity (EVA). For this MAP project, astronauts will perform a simple inhalation-exhalation procedure weekly during their flights, and before and after EVA. Furthermore, the microgravity environment offers a possibility to gain new insights into how and where NO is formed in the lungs and what local effects NO may have there. The planned experiments have been made possible by recent developments of new techniques by the team's industrial partners; Aerocrine has developed a highly compact and accurate NO analyser, and Linde Gas Theapeutics has developed a highly compact device for NO administration in the inhaled air.

  10. Airway epithelial homeostasis and planar cell polarity signaling depend on multiciliated cell differentiation

    PubMed Central

    Vladar, Eszter K.; Nayak, Jayakar V.; Milla, Carlos E.; Axelrod, Jeffrey D.

    2016-01-01

    Motile airway cilia that propel contaminants out of the lung are oriented in a common direction by planar cell polarity (PCP) signaling, which localizes PCP protein complexes to opposite cell sides throughout the epithelium to orient cytoskeletal remodeling. In airway epithelia, PCP is determined in a 2-phase process. First, cell-cell communication via PCP complexes polarizes all cells with respect to the proximal-distal tissue axis. Second, during ciliogenesis, multiciliated cells (MCCs) undergo cytoskeletal remodeling to orient their cilia in the proximal direction. The second phase not only directs cilium polarization, but also consolidates polarization across the epithelium. Here, we demonstrate that in airway epithelia, PCP depends on MCC differentiation. PCP mutant epithelia have misaligned cilia, and also display defective barrier function and regeneration, indicating that PCP regulates multiple aspects of airway epithelial homeostasis. In humans, MCCs are often sparse in chronic inflammatory diseases, and these airways exhibit PCP dysfunction. The presence of insufficient MCCs impairs mucociliary clearance in part by disrupting PCP-driven polarization of the epithelium. Consistent with defective PCP, barrier function and regeneration are also disrupted. Pharmacological stimulation of MCC differentiation restores PCP and reverses these defects, suggesting its potential for broad therapeutic benefit in chronic inflammatory disease. PMID:27570836

  11. Pluripotent Allospecific CD8+ Effector T Cells Traffic to Lung in Murine Obliterative Airway Disease

    PubMed Central

    West, Erin E.; Lavoie, Tera L.; Orens, Jonathan B.; Chen, Edward S.; Ye, Shui Q.; Finkelman, Fred D.; Garcia, Joe G. N.; McDyer, John F.

    2006-01-01

    Long-term success in lung transplantation is limited by obliterative bronchiolitis, whereas T cell effector mechanisms in this process remain incompletely understood. Using the mouse heterotopic allogeneic airway transplant model, we studied T cell effector responses during obliterative airways disease (OAD). Allospecific CD8+IFN-γ+ T cells were detected in airway allografts, with significant coexpression of TNF-α and granzyme B. Therefore, using IFN-γ as a surrogate marker, we assessed the distribution and kinetics of extragraft allo-specific T cells during OAD. Robust allospecific IFN-γ was produced by draining the lymph nodes, spleen, and lung mononuclear cells from allograft, but not isograft recipients by Day 14, and significantly decreased by Day 28. Although the majority of allospecific T cells were CD8+, allospecific CD4+ T cells were also detected in these compartments, with each employing distinct allorecognition pathways. An influx of pluripotent CD8+ effector cells with a memory phenotype were detected in the lung during OAD similar to those seen in the allografts and secondary lymphoid tissue. Antibody depletion of CD8+ T cells markedly reduced airway lumen obliteration and fibrosis at Day 28. Together, these data demonstrate that allospecific CD8+ effector T cells play an important role in OAD and traffic to the lung after heterotopic airway transplant, suggesting that the lung is an important immunologic site, and perhaps a reservoir, for effector cells during the rejection process. PMID:16195540

  12. Suppression of allergic airway inflammation in a mouse model of asthma by exogenous mesenchymal stem cells.

    PubMed

    Ou-Yang, Hai-Feng; Huang, Yun; Hu, Xing-Bin; Wu, Chang-Gui

    2011-12-01

    Mesenchymal stem cells (MSCs) have significant immunomodulatory effects in the development of acute lung inflammation and fibrosis. However, it is still unclear as to whether MSCs could attenuate allergic airway inflammation in a mouse model of asthma. We firstly investigated whether exogenous MSCs can relocate to lung tissues in asthmatic mice and analyzed the chemotactic mechanism. Then, we evaluated the in vivo immunomodulatory effect of exogenous MSCs in asthma. MSCs (2 × 10(6)) were administered through the tail vein to mice one day before the first airway challenge. Migration of MSCs was evaluated by flow cytometry. The immunomodulatory effect of MSCs was evaluated by cell counting in bronchoalveolar lavage fluid (BALF), histology, mast cell degranulation, airway hyperreactivity and cytokine profile in BALF. Exogenous MSCs can migrate to sites of inflammation in asthmatic mice through a stromal cell-derived factor-1α/CXCR4-dependent mechanism. MSCs can protect mice against a range of allergic airway inflammatory pathologies, including the infiltration of inflammatory cells, mast cell degranulation and airway hyperreactivity partly via shifting to a T-helper 1 (Th1) from a Th2 immune response to allergens. So, immunotherapy based on MSCs may be a feasible, efficient therapy for asthma. PMID:22114062

  13. The active contribution of Toll-like receptors to allergic airway inflammation.

    PubMed

    Chen, Keqiang; Xiang, Yi; Yao, Xiaohong; Liu, Ying; Gong, Wanghua; Yoshimura, Teizo; Wang, Ji Ming

    2011-10-01

    Epithelia lining the respiratory tract represent a major portal of entry for microorganisms and allergens and are equipped with innate and adaptive immune signaling receptors for host protection. These include Toll-like receptors (TLRs) that recognize microbial components and evoke diverse responses in cells of the respiratory system. TLR stimulation by microorganism-derived molecules activates antigen presenting cells, control T helper (Th) 1, Th2, and Th17 immune cell differentiation, cytokine production by mast cells, and activation of eosinophils. It is clear that TLR are involved in the pathophysiology of allergic airway diseases such as asthma. Dendritic cells (DCs), a kind of antigen presenting cells, which play a key role in the induction of allergic airway inflammation, are privileged targets for pathogen associated molecular patterns (PAMPs). During the allergic responses, engagement of TLRs on DCs determines the Th2 polarization of the T cells. TLR signaling in mast cells increases the release of IL-5, and TLR activation of airway epithelial cells forces the generation of proallergic Th2 type of cytokines. Although these responses aim to protect the host, they may also result in inflammatory tissue damage in the airway. Under certain conditions, stimulation of TLRs, in particular, TLR9, may reduce Th2-dependent allergic inflammation by induction of Th1 responses. Therefore, understanding the complex regulatory roles of TLRs in the pathogenesis of allergic airway inflammation should facilitate the development of preventive and therapeutic measures for asthmatic patients. PMID:21624504

  14. Mechanisms Linking Advanced Airway Management and Cardiac Arrest Outcomes

    PubMed Central

    Benoit, Justin L.; Prince, David K.; Wang, Henry E.

    2015-01-01

    Advanced airway management – such as endotracheal intubation (ETI) or supraglottic airway (SGA) insertion – is one of the most prominent interventions in out-of-hospital cardiac arrest (OHCA) resuscitation. While randomized controlled trials are currently in progress to identify the best advanced airway technique in OHCA, the mechanisms by which airway management may influence OHCA outcomes remain unknown. We provide a conceptual model describing potential mechanisms linking advanced airway management with OHCA outcomes. PMID:26073275

  15. Nasal airway responses to nasal continuous positive airway pressure breathing: An in-vivo pilot study.

    PubMed

    White, David E; Bartley, Jim; Shakeel, Muhammad; Nates, Roy J; Hankin, Robin K S

    2016-06-14

    The nasal cycle, through variation in nasal airflow partitioning, allows the upper airway to accommodate the contrasting demands of air conditioning and removal of entrapped air contaminants. The purpose of this study was to investigate the influence of nasal continuous positive airway pressure (nCPAP) breathing has on both nasal airflow partitioning and nasal geometry. Using a custom-made nasal mask, twenty healthy participants had the airflow in each naris measured during normal nasal breathing followed by nCPAP breathing. Eight participants also underwent magnetic resonance imaging (MRI) of the nasal region during spontaneous nasal breathing, and then nCPAP breathing over a range of air pressures. During nCPAP breathing, a simultaneous reduction in airflow through the patent airway together with a corresponding increase in airway flow within the congested nasal airway were observed in sixteen of the twenty participants. Nasal airflow resistance is inversely proportional to airway cross-sectional area. MRI data analysis during nCPAP breathing confirmed airway cross-sectional area reduced along the patent airway while the congested airway experienced an increase in this parameter. During awake breathing, nCPAP disturbs the normal inter-nasal airflow partitioning. This could partially explain the adverse nasal drying symptoms frequently reported by many users of this therapy. PMID:27173595

  16. Airway registry: a performance improvement surveillance project of emergency department airway management.

    PubMed

    Phelan, Michael P; Glauser, Jonathan; Yuen, Ho-Wang A; Sturges-Smith, Elizabeth; Schrump, Stefanie E

    2010-01-01

    The aim of this study was to determine if use of a standardized airway data collection sheet can survey airway management practices in an emergency department. Success rates and trends from the authors' facility have been benchmarked against the National Emergency Airway Registry (NEAR). This study included all patients requiring invasive airway management during a 21-month period (July 1, 2005, through March 31, 2007). An audit form was developed and implemented to collect data on intubations. During the study period, 224 patients required invasive airway control. Of all airways managed by emergency medicine residents, the intubation success rate was 99% (200/203; 95% confidence interval [CI] = 96%-100%), with 3% of those (6/203; 95% CI = 1%-6%) requiring more than 3 attempts; 3 patients (1%; 95% CI = 0%-4%) could not be intubated and required a surgical airway. Use of an airway registry based on the NEAR registry as a benchmark of rates and types of successful intubation allows comparison of airway practices. PMID:20505111

  17. 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

  18. BEHAVIOR OF CIGARETTE SMOKE IN HUMAN AIRWAYS

    EPA Science Inventory

    Experimental deposition patterns of cigarette smoke in surrogate human airway systems are very heterogeneous. article deposits are enhanced at predictable, well-defined morphological regions; most specifically, carinal ridges within bifurcation zones, and along posterior sections...

  19. 21 CFR 868.5810 - Airway connector.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... airway connector is a device intended to connect a breathing gas source to a tracheal tube, tracheostomy tube, or mask. (b) Classification. Class I (general controls). The device is exempt from the...

  20. 21 CFR 868.5810 - Airway connector.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... airway connector is a device intended to connect a breathing gas source to a tracheal tube, tracheostomy tube, or mask. (b) Classification. Class I (general controls). The device is exempt from the...

  1. 21 CFR 868.5810 - Airway connector.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... airway connector is a device intended to connect a breathing gas source to a tracheal tube, tracheostomy tube, or mask. (b) Classification. Class I (general controls). The device is exempt from the...

  2. 21 CFR 868.5810 - Airway connector.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... airway connector is a device intended to connect a breathing gas source to a tracheal tube, tracheostomy tube, or mask. (b) Classification. Class I (general controls). The device is exempt from the...

  3. Diesel exhaust particles and airway inflammation

    EPA Science Inventory

    Purpose of review. Epidemiologic investigation has associated traffic-related air pollution with adverse human health outcomes. The capacity ofdiesel exhaust particles (DEP), a major emission source air pollution particle, to initiate an airway inflammation has subsequently been ...

  4. 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

  5. Virtual Airway Skills Trainer (VAST) Simulator.

    PubMed

    Demirel, Doga; Yu, Alexander; Halic, Tansel; Sankaranarayanan, Ganesh; Ryason, Adam; Spindler, David; Butler, Kathryn L; Cao, Caroline; Petrusa, Emil; Molina, Marcos; Jones, Dan; De, Suvranu; Demoya, Marc; Jones, Stephanie

    2016-01-01

    This paper presents a simulation of Virtual Airway Skill Trainer (VAST) tasks. The simulated tasks are a part of two main airway management techniques; Endotracheal Intubation (ETI) and Cricothyroidotomy (CCT). ETI is a simple nonsurgical airway management technique, while CCT is the extreme surgical alternative to secure the airway of a patient. We developed identification of Mallampati class, finding the optimal angle for positioning pharyngeal/mouth axes tasks for ETI and identification of anatomical landmarks and incision tasks for CCT. Both ETI and CCT simulators were used to get physicians' feedback at Society for Education in Anesthesiology and Association for Surgical Education spring meetings. In this preliminary validation study, total 38 participants for ETI and 48 for CCT performed each simulation task and completed pre and post questionnaires. In this work, we present the details of the simulation for the tasks and also the analysis of the collected data from the validation study. PMID:27046559

  6. Airway management for cervical spine surgery.

    PubMed

    Farag, Ehab

    2016-03-01

    Cervical spine surgery is one of the most commonly performed spine surgeries in the United States, and 90% of the cases are related to degenerative cervical spine disease (the rest to cervical spine trauma and/or instability). The airway management for cervical spine surgery represents a crucial step in the anesthetic management to avoid injury to the cervical cord. The crux for upper airway management for cervical spine surgery is maintaining the neck in a neutral position with minimal neck movement during endotracheal intubation. Therefore, the conventional direct laryngoscopy (DL) can be unsuitable for securing the upper airway in cervical spine surgery, especially in cases of cervical spine instability and myelopathy. This review discusses the most recent evidence-based facts of the main advantages and limitations of different techniques available for upper airway management for cervical spine surgery. PMID:27036600

  7. Exploiting the relationship between birefringence and force to measure airway smooth muscle contraction with PS-OCT (Conference Presentation)

    NASA Astrophysics Data System (ADS)

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

    2016-03-01

    The ability to observe airway dynamics is fundamental to forming a complete understanding of pulmonary diseases such as asthma. We have previously demonstrated that Optical Coherence Tomography (OCT) can be used to observe structural changes in the airway during bronchoconstriction, but standard OCT lacks the contrast to discriminate airway smooth muscle (ASM) bands- ASM being responsible for generating the force that drives airway constriction- from the surrounding tissue. Since ASM in general exhibits a greater degree of birefringence than the surrounding tissue, a potential solution to this problem lies in the implementation of polarization sensitivity (PS) to the OCT system. By modifying the OCT system so that it is sensitive to the birefringence of tissue under inspection, we can visualize the ASM with much greater clarity and definition. In this presentation we show that the force of contraction can be indirectly measured by an associated increase in the birefringence signal of the ASM. We validate this approach by attaching segments of swine trachea to an isometric force transducer and stimulating contraction, while simultaneously measuring the exerted force and imaging the segment with PS-OCT. We then show how our results may be used to extrapolate the force of contraction of closed airways in absence of additional measurement devices. We apply this technique to assess ASM contractility volumetrically and in vivo, in both asthmatic and non-asthmatic human volunteers.

  8. Endotracheal Tube Management and Obstructed Airway.

    PubMed

    Sancheti, Manu; Force, Seth

    2015-08-01

    Thoracic surgery encompasses a wide array of surgical techniques, most of which require lung isolation for surgical exposure in the pleural cavity; this, in turn, demands an extensive knowledge of respiratory mechanics and modalities of airway control. Likewise, effective treatment of an acute central airway obstruction calls for a systematic approach using clear communication between teams and a comprehensive knowledge of available therapeutic modalities by the surgeon. PMID:26210924

  9. Medical management considerations for upper airway disease.

    PubMed

    Spaulding, G L

    1992-06-01

    The conducting airways, also commonly referred to as the upper airways, provide for the passage of air to and from the atmosphere and lungs. Anatomical components include the nasal passages, pharynx, larynx, trachea, and mainstem bronchi. Clinical problems involving the conducting airways can be manifested by relatively mild clinical signs of stertorous breathing, by life-threatening dyspnea, or by chronic bouts of inspiratory stridor and cough. Concurrent disease of the lower respiratory system (ie, chronic bronchitis) as well as other organ systems (ie, cardiovascular, nervous, endocrine) may significantly contribute to the etiology and pathophysiology of upper airway disease. Diagnosis of the diseases of the conducting airways is primarily based on history and physical examination. The dynamic nature of some conditions, related to the phases of respiration, can make diagnosis more difficult. In addition to direct visualization, radiographic and endoscopic evaluation are often useful. Many upper airway problems, especially congenital conditions, lend themselves to surgical palliation that should be performed as early in life as possible. Medical management is often directed at treating underlying diseases and the relief of clinical signs. Historically, the use of variety of drugs have been advocated and frequently include decongestants, cough suppressants, bronchodilators, glucocorticoids, and antibiotics. However, their use may be detrimental and contraindicated. In addition, therapy for some conditions (ie, laryngeal paralysis and intrathoracic tracheal collapse) may be better directed at increasing airway muscle tone in order to stabilized airway patency. Therapeutic agents that may be useful include aspirin and digitalis. The overall objective to medical management must be to balance potential therapeutic benefit against untoward effects in order to minimize clinical signs and to improve the animal's quality of life. PMID:1643322

  10. Tracheal and airway collapse in dogs.

    PubMed

    Maggiore, Ann Della

    2014-01-01

    Tracheal and airway collapse (bronchomalacia) are common causes of chronic cough in middle-aged to older dogs where weakening of cartilage within the respiratory system leads to narrowing of airways, coughing, wheezing, and other secondary effects. Successful treatment involves correct identification of the problem, recognition of concurrent problems, and appropriate medical therapy. Surgical and noninvasive treatment options are becoming readily available, and it is important to understand indications for such procedures. PMID:24268337

  11. Basolateral chloride current in human airway epithelia.

    PubMed

    Itani, Omar A; Lamb, Fred S; Melvin, James E; Welsh, Michael J

    2007-10-01

    Electrolyte transport by airway epithelia regulates the quantity and composition of liquid covering the airways. Previous data indicate that airway epithelia can absorb NaCl. At the apical membrane, cystic fibrosis transmembrane conductance regulator (CFTR) provides a pathway for Cl(-) absorption. However, the pathways for basolateral Cl(-) exit are not well understood. Earlier studies, predominantly in cell lines, have reported that the basolateral membrane contains a Cl(-) conductance. However, the properties have varied substantially in different epithelia. To better understand the basolateral Cl(-) conductance in airway epithelia, we studied primary cultures of well-differentiated human airway epithelia. The basolateral membrane contained a Cl(-) current that was inhibited by 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS). The current-voltage relationship was nearly linear, and the halide selectivity was Cl(-) > Br(-) > I(-). Several signaling pathways increased the current, including elevation of cellular levels of cAMP, activation of protein kinase C (PKC), and reduction of pH. In contrast, increasing cell Ca(2+) and inducing cell swelling had no effect. The basolateral Cl(-) current was present in both cystic fibrosis (CF) and non-CF airway epithelia. Likewise, airway epithelia from wild-type mice and mice with disrupted genes for ClC-2 or ClC-3 all showed similar Cl(-) currents. These data suggest that the basolateral membrane of airway epithelia possesses a Cl(-) conductance that is not due to CFTR, ClC-2, or ClC-3. Its regulation by cAMP and PKC signaling pathways suggests that coordinated regulation of Cl(-) conductance in both apical and basolateral membranes may be important in controlling transepithelial Cl(-) movement. PMID:17660331

  12. Biosignature for airway inflammation in a house dust mite-challenged murine model of allergic asthma.

    PubMed

    Piyadasa, Hadeesha; Altieri, Anthony; Basu, Sujata; Schwartz, Jacquie; Halayko, Andrew J; Mookherjee, Neeloffer

    2016-01-01

    House dust mite (HDM) challenge is commonly used in murine models of allergic asthma for preclinical pathophysiological studies. However, few studies define objective readouts or biomarkers in this model. In this study we characterized immune responses and defined molecular markers that are specifically altered after HDM challenge. In this murine model, we used repeated HDM challenge for two weeks which induced hallmarks of allergic asthma seen in humans, including airway hyper-responsiveness (AHR) and elevated levels of circulating total and HDM-specific IgE and IgG1. Kinetic studies showed that at least 24 h after last HDM challenge results in significant AHR along with eosinophil infiltration in the lungs. Histologic assessment of lung revealed increased epithelial thickness and goblet cell hyperplasia, in the absence of airway wall collagen deposition, suggesting ongoing tissue repair concomitant with acute allergic lung inflammation. Thus, this model may be suitable to delineate airway inflammation processes that precede airway remodeling and development of fixed airway obstruction. We observed that a panel of cytokines e.g. IFN-γ, IL-1β, IL-4, IL-5, IL-6, KC, TNF-α, IL-13, IL-33, MDC and TARC were elevated in lung tissue and bronchoalveolar fluid, indicating local lung inflammation. However, levels of these cytokines remained unchanged in serum, reflecting lack of systemic inflammation in this model. Based on these findings, we further monitored the expression of 84 selected genes in lung tissues by quantitative real-time PCR array, and identified 31 mRNAs that were significantly up-regulated in lung tissue from HDM-challenged mice. These included genes associated with human asthma (e.g. clca3, ear11, il-13, il-13ra2, il-10, il-21, arg1 and chia1) and leukocyte recruitment in the lungs (e.g. ccl11, ccl12 and ccl24). This study describes a biosignature to enable broad and systematic interrogation of molecular mechanisms and intervention strategies for

  13. Trichobezoar Causing Airway Compromise during Esophagogastroduodenoscopy.

    PubMed

    Kao, Erica Y; Scalzitti, Nicholas J; Dion, Gregory R; Bowe, Sarah N

    2015-01-01

    Objectives. (1) Report the case of a 5-year-old female with trichotillomania and trichophagia that suffered airway compromise during esophagogastroduodenoscopy for removal of a trichobezoar. (2) Provide management recommendations for an unusual foreign body causing extubation and partial airway obstruction. Methods. Case report of a rare situation of airway compromise caused by a trichobezoar. Results. A 5-year-old patient underwent endoscopic retrieval of a gastric trichobezoar (hairball) by the gastroenterology service under general endotracheal anesthesia in a sedation unit. During removal, the hairball, due to its large size, dislodged the endotracheal tube, effectively extubating the patient. The bezoar became lodged at the cricopharyngeus muscle. Attempts to remove the bezoar or reintubation were unsuccessful. The child was able to be mask ventilated while the otolaryngology service was called. Direct laryngoscopy revealed a hairball partially obstructing the view of the glottis from its position in the postcricoid area. The hairball, still entrapped in the snare from the esophagoscope, was grasped with Magill forceps and slowly extracted. The patient was then reintubated and the airway and esophagus were reevaluated. Conclusions. Trichobezoar is an uncommon cause of airway foreign body. Careful attention to airway management during these and similar foreign body extractions can prevent inadvertent extubations. PMID:26457086

  14. 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

  15. Trichobezoar Causing Airway Compromise during Esophagogastroduodenoscopy

    PubMed Central

    Kao, Erica Y.; Scalzitti, Nicholas J.; Dion, Gregory R.; Bowe, Sarah N.

    2015-01-01

    Objectives. (1) Report the case of a 5-year-old female with trichotillomania and trichophagia that suffered airway compromise during esophagogastroduodenoscopy for removal of a trichobezoar. (2) Provide management recommendations for an unusual foreign body causing extubation and partial airway obstruction. Methods. Case report of a rare situation of airway compromise caused by a trichobezoar. Results. A 5-year-old patient underwent endoscopic retrieval of a gastric trichobezoar (hairball) by the gastroenterology service under general endotracheal anesthesia in a sedation unit. During removal, the hairball, due to its large size, dislodged the endotracheal tube, effectively extubating the patient. The bezoar became lodged at the cricopharyngeus muscle. Attempts to remove the bezoar or reintubation were unsuccessful. The child was able to be mask ventilated while the otolaryngology service was called. Direct laryngoscopy revealed a hairball partially obstructing the view of the glottis from its position in the postcricoid area. The hairball, still entrapped in the snare from the esophagoscope, was grasped with Magill forceps and slowly extracted. The patient was then reintubated and the airway and esophagus were reevaluated. Conclusions. Trichobezoar is an uncommon cause of airway foreign body. Careful attention to airway management during these and similar foreign body extractions can prevent inadvertent extubations. PMID:26457086

  16. Small Airway Dysfunction and Abnormal Exercise Responses

    PubMed Central

    Petsonk, Edward L.; Stansbury, Robert C.; Beeckman-Wagner, Lu-Ann; Long, Joshua L.; Wang, Mei Lin

    2016-01-01

    Rationale Coal mine dust exposure can cause symptoms and loss of lung function from multiple mechanisms, but the roles of each disease process are not fully understood. Objectives We investigated the implications of small airway dysfunction for exercise physiology among a group of workers exposed to coal mine dust. Methods Twenty coal miners performed spirometry, first breathing air and then helium-oxygen, single-breath diffusing capacity, and computerized chest tomography, and then completed cardiopulmonary exercise testing. Measurements and Main Results Six participants meeting criteria for small airway dysfunction were compared with 14 coal miners who did not. At submaximal workload, miners with small airway dysfunction used a higher proportion of their maximum voluntary ventilation and had higher ventilatory equivalents for both O2 and CO2. Regression modeling indicated that inefficient ventilation was significantly related to small airway dysfunction but not to FEV1 or diffusing capacity. At the end of exercise, miners with small airway dysfunction had 27% lower O2 consumption. Conclusions Small airway abnormalities may be associated with important inefficiency of exercise ventilation. In dust-exposed individuals with only mild abnormalities on resting lung function tests or chest radiographs, cardiopulmonary exercise testing may be important in defining causes of exercise intolerance. PMID:27073987

  17. Exercise-induced airways constriction 1

    PubMed Central

    Simonsson, Bo G.; Skoogh, B-E.; Ekström-Jodal, B.

    1972-01-01

    Airway conductance was measured in a body plethysmograph at different lung volumes before and after graded exercise. In 14 out of 19 patients, mostly asthmatics, airway conductance fell significantly after exercise. These subjects also showed other signs of an increased bronchial reactivity to different stimuli, including forced breathing, hyperventilation, and cold air, but they had no exogenous allergy. The exercise-induced bronchoconstriction could be blocked by atropine in six of the nine patients tested. Exercise-induced bronchoconstriction in patients with clinical and physiological evidence of increased airway reactivity thus seems to be primarily mediated via a vagal reflex, probably from hyperresponsive airway mechanoreceptors reacting to increased ventilatory flow or lung distension. No relation was found between PaCO2 or pH and the severity of airways constriction. Cromoglycic acid failed to block the exercise reaction in five of the six hyperreactive patients tested. In addition to or following the vagal reflex a disturbed relation between beta and alpha receptors in bronchial muscles or a release of humoral spasmogens may contribute to the progression of post-exercise airways constriction. PMID:4624586

  18. Mechanical Properties of the Upper Airway

    PubMed Central

    Strohl, Kingman P.; Butler, James P.; Malhotra, Atul

    2013-01-01

    The importance of the upper airway (nose, pharynx, and larynx) in health and in the pathogenesis of sleep apnea, asthma, and other airway diseases, discussed elsewhere in the Comprehensive Physiology series, prompts this review of the biomechanical properties and functional aspects of the upper airway. There is a literature based on anatomic or structural descriptions in static circumstances, albeit studied in limited numbers of individuals in both health and disease. As for dynamic features, the literature is limited to studies of pressure and flow through all or parts of the upper airway and to the effects of muscle activation on such features; however, the links between structure and function through airway size, shape, and compliance remain a topic that is completely open for investigation, particularly through analyses using concepts of fluid and structural mechanics. Throughout are included both historically seminal references, as well as those serving as signposts or updated reviews. This article should be considered a resource for concepts needed for the application of biomechanical models of upper airway physiology, applicable to understanding the pathophysiology of disease and anticipated results of treatment interventions. PMID:23723026

  19. Large-scale gene discovery in human airway epithelia reveals novel transcripts.

    PubMed

    Scheetz, Todd E; Zabner, Joseph; Welsh, Michael J; Coco, Justin; Eyestone, Mari de Fatima; Bonaldo, Maria; Kucaba, Tamara; Casavant, Thomas L; Soares, M Bento; McCray, Paul B

    2004-03-12

    The airway epithelium represents an important barrier between the host and the environment. It is a first site of contact with pathogens, particulates, and other stimuli, and has evolved the means to dynamically respond to these challenges. In an effort to define the transcript profile of airway epithelia, we created and sequenced cDNA libraries from cystic fibrosis (CF) and non-CF epithelia and from human lung tissue. Sequencing of these libraries produced approximately 53,000 3'-expressed sequence tags (3'-ESTs). From these, a nonredundant UniGene set of more than 19,000 sequences was generated. Despite the relatively small contribution of airway epithelia to the total mass of the lung, focused gene discovery in this tissue yielded novel results. The ESTs included several thousand transcripts (6,416) not previously identified from cDNA sequences as expressed in the lung. Among the abundant transcripts were several genes involved in host defense. Most importantly, the set also included 879 3'-ESTs that appear to be novel sequences not previously represented in the National Center for Biotechnology Information UniGene collection. This UniGene set should be useful for studies of pulmonary diseases involving the airway epithelium including cystic fibrosis, respiratory infections and asthma. It also provides a reagent for large-scale expression profiling. PMID:14701920

  20. Inflammatory responses of airway smooth muscle cells and effects of endothelin receptor antagonism.

    PubMed

    Knobloch, Jürgen; Lin, Yingfeng; Konradi, Jürgen; Jungck, David; Behr, Juergen; Strauch, Justus; Stoelben, Erich; Koch, Andrea

    2013-07-01

    Endothelin receptor antagonists (ETRAs), authorized for pulmonary hypertension, have failed to prove their utility in chronic lung diseases with corticosteroid-resistant airway inflammation when applied at late disease stages with emphysema/fibrosis. Earlier administration might prove effective by targeting the interaction between airway inflammation and tissue remodeling. We hypothesized that human airway smooth muscle cells (HASMCs) participate in linking inflammation with remodeling and that associated genes become differentially suppressed by ambrisentan (A-receptor selective ETRA) and bosentan (nonselective/dual ETRA). Inflammatory responses of ex vivo-cultivated HASMCs to TNF-α were investigated by whole-genome microarray analyses. qRT-PCR and ELISA were used to test inflammatory and remodeling genes for sensitivity to bosentan and ambrisentan and to investigate differential sensitivities mechanistically. ETRA and corticosteroid effects were compared in HASMCs from patients with chronic obstructive pulmonary disease. TNF-α induced the expression of 18 cytokines/chemokines and five tissue remodeling genes involved in severe, corticosteroid-insensitive asthma, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, and/or pulmonary hypertension. Thirteen cytokines/chemokines, MMP13, and WISP1 were suppressed by ETRAs. Eight genes had differential sensitivity to bosentan and ambrisentan depending on the endothelin-B receptor impact on transcriptional regulation and mRNA stabilization. Chemokine (C-C motif) ligands 2 and 5, granulocyte macrophage colony-stimulating factor, and MMP13 had increased sensitivity to bosentan or bosentan/dexamethasone combination versus dexamethasone alone. Suppression of cytokine and remodeling gene expression by ETRAs was confirmed in TNF-α-activated human bronchial epithelial cells. HASMCs and human bronchial epithelial cells participate in the interaction of inflammation and tissue remodeling. This interaction is

  1. Temporal Changes in Glutaredoxin 1 and Protein S-Glutathionylation in Allergic Airway Inflammation

    PubMed Central

    Maki, Kanako; Nagai, Katsura; Suzuki, Masaru; Inomata, Takashi; Yoshida, Takayuki; Nishimura, Masaharu

    2015-01-01

    Introduction Asthma is a chronic inflammatory disorder of the airways, involving oxidative stress. Upon oxidative stress, glutathione covalently binds to protein thiols to protect them against irreversible oxidation. This posttranslational modification, known as protein S-glutathionylation, can be reversed by glutaredoxin 1 (Glrx1) under physiological condition. Glrx1 is known to increase in the lung tissues of a murine model of allergic airway inflammation. However, the temporal relationship between levels of Glrx1, protein S-glutathionylation, and glutathione in the lungs with allergic airway inflammation is not clearly understood. Methods BALB/c mice received 3 aerosol challenges with ovalbumin (OVA) following sensitization to OVA. They were sacrificed at 6, 24, 48, or 72 h, or 8 days (5 mice per group), and the levels of Glrx1, protein S-glutathionylation, glutathione, and 25 cytokines/chemokines were evaluated in bronchoalveolar lavage fluid (BALF) and/or lung tissue. Results Levels of Glrx1 in BALF were significantly elevated in the OVA 6 h (final challenge) group compared to those in the control, with concurrent increases in protein S-glutathionylation levels in the lungs, as well as total glutathione (reduced and oxidized) and oxidized glutathione in BALF. Protein S-glutathionylation levels were attenuated at 24 h, with significant increases in Glrx1 levels in lung tissues at 48 and 72 h. Glrx1 in alveolar macrophages was induced after 6 h. Glrx1 levels concomitantly increased with Th2/NF-κB-related cytokines and chemokines in BALF. Conclusions The temporal relationships of Glrx1 with protein S-glutathionylation, glutathione, and cytokines/chemokines were observed as dynamic changes in lungs with allergic airway inflammation, suggesting that Glrx1 and protein–SSG redox status may play important roles in the development of allergic airway inflammation. PMID:25874776

  2. 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

  3. Detection and monitoring of early airway injury effects of half-mustard (2-chloroethylethylsulfide) exposure using high-resolution optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Kreuter, Kelly A.; Mahon, Sari B.; Mukai, David S.; Su, Jianping; Jung, Woong-Gyu; Narula, Navneet; Guo, Shuguang; Wakida, Nicole; Raub, Chris; Berns, Michael W.; George, Steven C.; Chen, Zhongping; Brenner, Matthew

    2009-07-01

    Optical coherence tomography (OCT) is a noninvasive, high-resolution imaging technology capable of delivering real-time, near-histologic images of tissues. Mustard gas is a vesicant-blistering agent that can cause severe and lethal damage to airway and lungs. The ability to detect and assess airway injury in the clinical setting of mustard exposure is currently limited. The purpose of this study is to assess the ability to detect and monitor progression of half-mustard [2-chloroethylethylsulfide (CEES)] airway injuries with OCT techniques. A ventilated rabbit mustard exposure airway injury model is developed. A flexible fiber optic OCT probe is introduced into the distal trachea to image airway epithelium and mucosa in vivo. Progression of airway injury is observed over eight hours with OCT using a prototype time-domain superluminescent diode OCT system. OCT tracheal images from CEES exposed animals are compared to control rabbits for airway mucosal thickening and other changes. OCT detects the early occurrence and progression of dramatic changes in the experimental group after exposure to CEES. Histology and immunofluorescence staining confirms this finding. OCT has the potential to be a high resolution imaging modality capable of detecting, assessing, and monitoring treatment for airway injury following mustard vesicant agent exposures.

  4. Detection and monitoring of early airway injury effects of half-mustard (2-chloroethylethylsulfide) exposure using high-resolution optical coherence tomography

    PubMed Central

    Kreuter, Kelly A.; Mahon, Sari B.; Mukai, David S.; Su, Jianping; Jung, Woong-Gyu; Narula, Navneet; Guo, Shuguang; Wakida, Nicole; Raub, Chris; Berns, Michael W.; George, Steven C.; Chen, Zhongping; Brenner, Matthew

    2009-01-01

    Optical coherence tomography (OCT) is a non-invasive, high-resolution imaging technology capable of delivering real-time, near-histologic images of tissues. Mustard gas is a vesicant-blistering agent that can cause severe and lethal damage to airway and lungs. The ability to detect and assess airway injury in the clinical setting of mustard exposure is currently limited. The purpose of this study is to assess the ability to detect and monitor progression of half-mustard [2-chloroethylethylsulfide (CEES)] airway injuries with OCT techniques. A ventilated rabbit mustard exposure airway injury model is developed. A flexible fiber optic OCT probe is introduced into the distal trachea to image airway epithelium and mucosa in vivo. Progression of airway injury is observed over eight hours with OCT using a prototype time-domain superluminescent diode OCT system. OCT tracheal images from CEES exposed animals are compared to control rabbits for airway mucosal thickening and other changes. OCT detects the early occurrence and progression of dramatic changes in the experimental group after exposure to CEES. Histology and immunofluorescence staining confirms this finding. OCT has the potential to be a high resolution imaging modality capable of detecting, assessing, and monitoring treatment for airway injury following mustard vesicant agent exposures. PMID:19725748

  5. Origins of increased airway smooth muscle mass in asthma.

    PubMed

    Berair, Rachid; Saunders, Ruth; Brightling, Christopher E

    2013-01-01

    Asthma is characterized by both chronic inflammation and airway remodeling. Remodeling--the structural changes seen in asthmatic airways--is pivotal in the pathogenesis of the disease. Although significant advances have been made recently in understanding the different aspects of airway remodeling, the exact biology governing these changes remains poorly understood. There is broad agreement that, in asthma, increased airway smooth muscle mass, in part due to smooth muscle hyperplasia, is a very significant component of airway remodeling. However, significant debate persists on the origins of these airway smooth muscle cells. In this review article we will explore the natural history of airway remodeling in asthma and we will discuss the possible contribution of progenitors, stem cells and epithelial cells in mesenchymal cell changes, namely airway smooth muscle hyperplasia seen in the asthmatic airways. PMID:23742314

  6. Lubiprostone targets prostanoid EP4 receptors in ovine airways

    PubMed Central

    Cuthbert, AW

    2011-01-01

    BACKGROUND AND PURPOSE Lubiprostone, a prostaglandin E1 derivative, is reported to activate ClC-2 chloride channels located in the apical membranes of a number of transporting epithelia. Lack of functioning CFTR chloride channels in epithelia is responsible for the genetic disease cystic fibrosis, therefore, surrogate channels that can operate independently of CFTR are of interest. This study explores the target receptor(s) for lubiprostone in airway epithelium. EXPERIMENTAL APPROACH All experiments were performed on the ventral tracheal epithelium of sheep. Epithelia were used to measure anion secretion from the apical surface as short circuit current or as fluid secretion from individual airway submucosal glands, using an optical method. KEY RESULTS The EP4 antagonists L-161982 and GW627368 inhibited short circuit current responses to lubiprostone, while EP1,2&3 receptor antagonists were without effect. Similarly, lubiprostone induced secretion in airway submucosal glands was inhibited by L-161982. L-161982 effectively competed with lubiprostone with a Kd value of 0.058 µM, close to its value for binding to human EP4 receptors (0.024 µM). The selective EP4 agonist L-902688 and lubiprostone behaved similarly with respect to EP4 receptor antagonists. Results of experiments with H89, a protein kinase A inhibitor, were consistent with lubiprostone acting through a Gs-protein coupled EP4 receptor/cAMP cascade. CONCLUSIONS AND IMPLICATIONS Lubiprostone-induced short-circuit currents and submucosal gland secretions were inhibited by selective EP4 receptor antagonists. The results suggest EP4 receptor activation by lubiprostone triggers cAMP production necessary for CFTR activation and the secretory responses, a possibility precluded in CF tissues. PMID:20883477

  7. The relation of airway size to lung function

    NASA Astrophysics Data System (ADS)

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

    2008-03-01

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

  8. Two-dimensional airway analysis using probabilistic neural networks

    NASA Astrophysics Data System (ADS)

    Tan, Jun; Zheng, Bin; Park, Sang Cheol; Pu, Jiantao; Sciurba, Frank C.; Leader, Joseph K.

    2010-03-01

    Although 3-D airway tree segmentation permits analysis of airway tree paths of practical lengths and facilitates visual inspection, our group developed and tested an automated computer scheme that was operated on individual 2-D CT images to detect airway sections and measure their morphometry and/or dimensions. The algorithm computes a set of airway features including airway lumen area (Ai), airway cross-sectional area (Aw), the ratio (Ra) of Ai to Aw, and the airway wall thickness (Tw) for each detected airway section depicted on the CT image slice. Thus, this 2-D based algorithm does not depend on the accuracy of 3-D airway tree segmentation and does not require that CT examination encompasses the entire lung or reconstructs contiguous images. However, one disadvantage of the 2-D image based schemes is the lack of the ability to identify the airway generation (Gb) of the detected airway section. In this study, we developed and tested a new approach that uses 2-D airway features to assign a generation number to an airway. We developed and tested two probabilistic neural networks (PNN) based on different sets of airway features computed by our 2-D based scheme. The PNNs were trained and tested on 12 lung CT examinations (8 training and 4 testing). The accuracy for the PNN that utilized Ai and Ra for identifying the generation of airway sections varies from 55.4% - 100%. The overall accuracy of the PNN for all detected airway sections that are spread over all generations is 76.7%. Interestingly, adding wall thickness feature (Tw) to PNN did not improve identification accuracy. This preliminary study demonstrates that a set of 2-D airway features may be used to identify the generation number of an airway with reasonable accuracy.

  9. 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

  10. The use of laryngeal mask airway Supreme™ in rescue airway situation in the critical care unit.

    PubMed

    Siddiqui, Shahla; Seet, Edwin; Chan, Wing Yan

    2014-12-01

    We herein report a witnessed cardiopulmonary collapse of a patient with difficult mask ventilation and near-impossible laryngoscopy-cum-intubation in the critical care unit. The airway was successfully rescued with a laryngeal mask airway Supreme™, followed by an open, crash tracheostomy by the otolaryngologist. PMID:25630328

  11. Epithelium damage and protection during reopening of occluded airways in a physiologic microfluidic pulmonary airway model.

    PubMed

    Tavana, Hossein; Zamankhan, Parsa; Christensen, Paul J; Grotberg, James B; Takayama, Shuichi

    2011-08-01

    Airways of the peripheral lung are prone to closure at low lung volumes. Deficiency or dysfunction of pulmonary surfactant during various lung diseases compounds this event by destabilizing the liquid lining of small airways and giving rise to occluding liquid plugs in airways. Propagation of liquid plugs in airways during inflation of the lung exerts large mechanical forces on airway cells. We describe a microfluidic model of small airways of the lung that mimics airway architecture, recreates physiologic levels of pulmonary pressures, and allows studying cellular response to repeated liquid plug propagation events. Substantial cellular injury happens due to the propagation of liquid plugs devoid of surfactant. We show that addition of a physiologic concentration of a clinical surfactant, Survanta, to propagating liquid plugs protects the epithelium and significantly reduces cell death. Although the protective role of surfactants has been demonstrated in models of a propagating air finger in liquid-filled airways, this is the first time to study the protective role of surfactants in liquid plugs where fluid mechanical stresses are expected to be higher than in air fingers. Our parallel computational simulations revealed a significant decrease in mechanical forces in the presence of surfactant, confirming the experimental observations. The results support the practice of providing exogenous surfactant to patients in certain clinical settings as a protective mechanism against pathologic flows. More importantly, this platform provides a useful model to investigate various surface tension-mediated lung diseases at the cellular level. PMID:21487664

  12. Nucleotide-mediated airway clearance.

    PubMed

    Schmid, Andreas; Clunes, Lucy A; Salathe, Mathias; Verdugo, Pedro; Dietl, Paul; Davis, C William; Tarran, Robert

    2011-01-01

    A thin layer of airway surface liquid (ASL) lines the entire surface of the lung and is the first point of contact between the lung and the environment. Surfactants contained within this layer are secreted in the alveolar region and are required to maintain a low surface tension and to prevent alveolar collapse. Mucins are secreted into the ASL throughout the respiratory tract and serve to intercept inhaled pathogens, allergens and toxins. Their removal by mucociliary clearance (MCC) is facilitated by cilia beating and hydration of the ASL by active ion transport. Throughout the lung, secretion, ion transport and cilia beating are under purinergic control. Pulmonary epithelia release ATP into the ASL which acts in an autocrine fashion on P2Y(2) (ATP) receptors. The enzymatic network describes in Chap. 2 then mounts a secondary wave of signaling by surface conversion of ATP into adenosine (ADO), which induces A(2B) (ADO) receptor-mediated responses. This chapter offers a comprehensive description of MCC and the extensive ramifications of the purinergic signaling network on pulmonary surfaces. PMID:21560046

  13. Vectors for airway gene delivery.

    PubMed

    Davis, Pamela B; Cooper, Mark J

    2007-01-01

    Delivery of genes to the airway epithelium for therapeutic purposes seemed easy at first, because the epithelial cells interface with the environment and are therefore accessible. However, problems encountered were more substantial than were originally expected. Nonviral systems may be preferred for long-term gene expression, for they can be dosed repeatedly. Two nonviral gene transfer systems have been in clinical trials, lipid-mediated gene transfer and DNA nanoparticles. Both have sufficient efficiency to be candidates for correction of the cystic fibrosis defect, and both can be dosed repeatedly. However, lipid-mediated gene transfer in the first generation provokes significant inflammatory toxicity, which may be engineered out by adjustments of the lipids, the plasmid CpG content, or both. Both lipid-mediated gene transfer and DNA nanoparticles in the first generation have short duration of expression, but reengineering of the plasmid DNA to contain mostly eukaryotic sequences may address this problem. Considerable advances in the understanding of the cellular uptake and expression of these agents and in their practical utility have occurred in the last few years; these advances are reviewed here. PMID:17408235

  14. The Effects of Tumstatin on Vascularity, Airway Inflammation and Lung Function in an Experimental Sheep Model of Chronic Asthma.

    PubMed

    Van der Velden, Joanne; Harkness, Louise M; Barker, Donna M; Barcham, Garry J; Ugalde, Cathryn L; Koumoundouros, Emmanuel; Bao, Heidi; Organ, Louise A; Tokanovic, Ana; Burgess, Janette K; Snibson, Kenneth J

    2016-01-01

    Tumstatin, a protein fragment of the alpha-3 chain of Collagen IV, is known to be significantly reduced in the airways of asthmatics. Further, there is evidence that suggests a link between the relatively low level of tumstatin and the induction of angiogenesis and inflammation in allergic airway disease. Here, we show that the intra-segmental administration of tumstatin can impede the development of vascular remodelling and allergic inflammatory responses that are induced in a segmental challenge model of experimental asthma in sheep. In particular, the administration of tumstatin to lung segments chronically exposed to house dust mite (HDM) resulted in a significant reduction of airway small blood vessels in the diameter range 10(+)-20 μm compared to controls. In tumstatin treated lung segments after HDM challenge, the number of eosinophils was significantly reduced in parenchymal and airway wall tissues, as well as in the bronchoalveolar lavage fluid. The expression of VEGF in airway smooth muscle was also significantly reduced in tumstatin-treated segments compared to control saline-treated segments. Allergic lung function responses were not attenuated by tumstatin administration in this model. The data are consistent with the concept that tumstatin can act to suppress vascular remodelling and inflammation in allergic airway disease. PMID:27199164

  15. The Effects of Tumstatin on Vascularity, Airway Inflammation and Lung Function in an Experimental Sheep Model of Chronic Asthma

    PubMed Central

    Van der Velden, Joanne; Harkness, Louise M.; Barker, Donna M.; Barcham, Garry J.; Ugalde, Cathryn L.; Koumoundouros, Emmanuel; Bao, Heidi; Organ, Louise A.; Tokanovic, Ana; Burgess, Janette K.; Snibson, Kenneth J.

    2016-01-01

    Tumstatin, a protein fragment of the alpha-3 chain of Collagen IV, is known to be significantly reduced in the airways of asthmatics. Further, there is evidence that suggests a link between the relatively low level of tumstatin and the induction of angiogenesis and inflammation in allergic airway disease. Here, we show that the intra-segmental administration of tumstatin can impede the development of vascular remodelling and allergic inflammatory responses that are induced in a segmental challenge model of experimental asthma in sheep. In particular, the administration of tumstatin to lung segments chronically exposed to house dust mite (HDM) resulted in a significant reduction of airway small blood vessels in the diameter range 10+–20 μm compared to controls. In tumstatin treated lung segments after HDM challenge, the number of eosinophils was significantly reduced in parenchymal and airway wall tissues, as well as in the bronchoalveolar lavage fluid. The expression of VEGF in airway smooth muscle was also significantly reduced in tumstatin-treated segments compared to control saline-treated segments. Allergic lung function responses were not attenuated by tumstatin administration in this model. The data are consistent with the concept that tumstatin can act to suppress vascular remodelling and inflammation in allergic airway disease. PMID:27199164

  16. Rho-associated protein kinase inhibition enhances airway epithelial Basal-cell proliferation and lentivirus transduction.

    PubMed

    Horani, Amjad; Nath, Aditya; Wasserman, Mollie G; Huang, Tao; Brody, Steven L

    2013-09-01

    The identification of factors that regulate airway epithelial cell proliferation and differentiation are essential for understanding the pathophysiology of airway diseases. Rho-associated protein kinases (ROCKs) are downstream effector proteins of RhoA GTPase that direct the functions of cell cytoskeletal proteins. ROCK inhibition with Y27632 has been shown to enhance the survival and cloning of human embryonic stem cells and pluripotent cells in other tissues. We hypothesized that Y27632 treatment exerts a similar effect on airway epithelial basal cells, which function as airway epithelial progenitor cells. Treatment with Y27632 enhanced basal-cell proliferation in cultured human tracheobronchial and mouse tracheal epithelial cells. ROCK inhibition accelerated the maturation of basal cells, characterized by a diminution of the cell size associated with cell compaction and the expression of E-cadherin at cell-cell junctions. Transient treatment of cultured basal cells with Y27632 did not affect subsequent ciliated or mucous cell differentiation under air-liquid interface conditions, and allowed for the initial use of lower numbers of human or mouse primary airway epithelial cells than otherwise possible. Moreover, the use of Y27632 during lentivirus-mediated transduction significantly improved posttransduction efficiency and the selection of a transduced cell population, as determined by reporter gene expression. These findings suggest an important role for ROCKs in the regulation of proliferation and maturation of epithelial basal cells, and demonstrate that the inhibition of ROCK pathways using Y27632 provides an adjunctive tool for the in vitro genetic manipulation of airway epithelial cells by lentivirus vectors. PMID:23713995

  17. Endobronchial Ultrasound Reliably Quantifies Airway Smooth Muscle Remodeling in an Equine Asthma Model.

    PubMed

    Bullone, Michela; Beauchamp, Guy; Godbout, Mireille; Martin, James G; Lavoie, Jean-Pierre

    2015-01-01

    Endobronchial ultrasonography (EBUS) revealed differences in the thickness of the layer representing subepithelial tissues (L2) between human asthmatics and controls, but whether this measurement correlates with airway smooth muscle (ASM) remodeling in asthma is unknown. In this study, we sought to determine the ability of EBUS to predict histological ASM remodeling in normal and equine asthmatic airways. We studied 109 isolated bronchi from the lungs of 13 horses. They underwent EBUS examination using a 30 MHz radial probe before being processed for histology. ASM remodeling parameters were evaluated in EBUS images (L2 thickness, L2 area, L2 area/internal perimeter [Pi] and L2 area/Pi2) and histological cuts (ASM area/Pi2), and compared. EBUS was then performed ex vivo on the lungs of 4 horses with heaves, an asthma-like condition of horses, and 7 controls to determine whether central bronchial remodeling could be detected with this technique. An optimized approach was developed based on data variability within airways, subjects, and groups, and then validated in 7 horses (3 controls, 4 with heaves) that underwent EBUS in vivo. L2 area was significantly associated to ASM area in isolated lungs (p<0.0001), in the absence of significant bias related to the airway size. Bronchial size significantly affected EBUS ASM-related parameters, except for L2 area/Pi2. L2 area/Pi2 was increased in the airways of asthmatic horses compared to controls, both ex vivo and in vivo (p<0.05). Bronchial histology confirmed our findings (AASM/Pi2 was increased in asthmatic horses compared to controls, p<0.05). In both horses with heaves and controls, L2 was composed of ASM for the outer 75% of its thickness and by ECM for the remaining inner 25%. In conclusion, EBUS reliably allows assessment of asthma-associated ASM remodeling of central airways in a non-invasive way. PMID:26348727

  18. Ground truth and CT image model simulation for pathophysiological human airway system

    NASA Astrophysics Data System (ADS)

    Ortner, Margarete; Fetita, Catalin; Brillet, Pierre-Yves; Pr"teux, Françoise; Grenier, Philippe

    2010-02-01

    Recurrent problem in medical image segmentation and analysis, establishing a ground truth for assessment purposes is often difficult. Facing this problem, the scientific community orients its efforts towards the development of objective methods for evaluation, namely by building up or simulating the missing ground truth for analysis. This paper focuses on the case of human pulmonary airways and develops a method 1) to simulate the ground truth for different pathophysiological configurations of the bronchial tree as a mesh model, and 2) to generate synthetic 3D CT images of airways associated with the simulated ground truth. The airway model is here built up based on the information provided by a medial axis (describing bronchus shape, subdivision geometry and local radii), which is computed from real CT data to ensure realism and matching with a patient-specific morphology. The model parameters can be further on adjusted to simulate various pathophysiological conditions of the same patient (longitudinal studies). Based on the airway mesh model, a 3D image model is synthesized by simulating the CT acquisition process. The image realism is achieved by including textural features of the surrounding pulmonary tissue which are obtained by segmentation from the same original CT data providing the airway axis. By varying the scanning simulation parameters, several 3D image models can be generated for the same airway mesh ground truth. Simulation results for physiological and pathological configurations are presented and discussed, illustrating the interest of such a modeling process for designing computer-aided diagnosis systems or for assessing their sensitivity, mainly for follow-up studies in asthma and COPD.

  19. Pim1 kinase activity preserves airway epithelial integrity upon house dust mite exposure.

    PubMed

    de Vries, M; Hesse, L; Jonker, M R; van den Berge, M; van Oosterhout, A J M; Heijink, I H; Nawijn, M C

    2015-12-01

    Most patients with allergic asthma are sensitized to house dust mite (HDM). The allergenicity of HDM largely depends on disruption of the integrity and proinflammatory activation of the airway epithelium. In this study, we hypothesized that Pim1 kinase activity attenuates HDM-induced asthma by preserving airway epithelial integrity. The effects of Pim1 kinase activity on barrier function and release of the proinflammatory mediators IL-1α and CCL20 were studied in vitro in 16HBE and primary bronchial epithelial cells (PBECs). Pim1-proficient and -deficient mice were exposed to a HDM-driven model of allergic asthma, and airway hyperresponsiveness (AHR) was measured upon methacholine challenge. Airway inflammation and proinflammatory mediators in lung tissue and BAL fluid were determined. We observed that inhibition of Pim1 kinase prolongs the HDM-induced loss of barrier function in 16HBE cells and sensitizes PBECs to HDM-induced barrier dysfunction. Additionally, inhibition of Pim1 kinase increased the HDM-induced proinflammatory activity of 16HBE cells as measured by IL-1α secretion. In line herewith, HDM exposure induced an enhanced production of the proinflammatory chemokines CCL17 and CCL20 in Pim1-deficient mice compared with wild-type controls. While we observed a marked increase in eosinophilic and neutrophilic granulocytes as well as mucus cell metaplasia and AHR to methacholine in mice exposed to HDM, these parameters were independent of Pim1 kinase activity. In contrast, levels of the Th2-cytokines IL-5 and IL-10 were significantly augmented in HDM-treated Pim1-deficient mice. Taken together, our study shows that Pim1 kinase activity maintains airway epithelial integrity and protects against HDM-induced proinflammatory activation of the airway epithelium. PMID:26453516

  20. Endobronchial Ultrasound Reliably Quantifies Airway Smooth Muscle Remodeling in an Equine Asthma Model

    PubMed Central

    Bullone, Michela; Beauchamp, Guy; Godbout, Mireille; Martin, James G.; Lavoie, Jean-Pierre

    2015-01-01

    Endobronchial ultrasonography (EBUS) revealed differences in the thickness of the layer representing subepithelial tissues (L2) between human asthmatics and controls, but whether this measurement correlates with airway smooth muscle (ASM) remodeling in asthma is unknown. In this study, we sought to determine the ability of EBUS to predict histological ASM remodeling in normal and equine asthmatic airways. We studied 109 isolated bronchi from the lungs of 13 horses. They underwent EBUS examination using a 30 MHz radial probe before being processed for histology. ASM remodeling parameters were evaluated in EBUS images (L2 thickness, L2 area, L2 area/internal perimeter [Pi] and L2 area/Pi2) and histological cuts (ASM area/Pi2), and compared. EBUS was then performed ex vivo on the lungs of 4 horses with heaves, an asthma-like condition of horses, and 7 controls to determine whether central bronchial remodeling could be detected with this technique. An optimized approach was developed based on data variability within airways, subjects, and groups, and then validated in 7 horses (3 controls, 4 with heaves) that underwent EBUS in vivo. L2 area was significantly associated to ASM area in isolated lungs (p<0.0001), in the absence of significant bias related to the airway size. Bronchial size significantly affected EBUS ASM-related parameters, except for L2 area/Pi2. L2 area/Pi2 was increased in the airways of asthmatic horses compared to controls, both ex vivo and in vivo (p<0.05). Bronchial histology confirmed our findings (AASM/Pi2 was increased in asthmatic horses compared to controls, p<0.05). In both horses with heaves and controls, L2 was composed of ASM for the outer 75% of its thickness and by ECM for the remaining inner 25%. In conclusion, EBUS reliably allows assessment of asthma-associated ASM remodeling of central airways in a non-invasive way. PMID:26348727

  1. Influenza A infection enhances antigen-induced airway inflammation and hyper-responsiveness in young but not aged mice

    PubMed Central

    Birmingham, Janette M.; Gillespie, Virginia L.; Srivastava, Kamal; Li, Xiu-Min; Busse, Paula J.

    2015-01-01

    Background Although morbidity and mortality rates from asthma are highest in patients > 65 years of age, the effect of older age on airway inflammation in asthma is not well established. Objective To investigate age-related differences in the promotion of allergic inflammation after influenza A viral respiratory infection on antigen specific IgE production, antigen-induced airway inflammation and airway hyper-responsiveness in mice. Methods To accomplish this objective, the following model system was used. Young (six-week) and aged (18-month) BALB/c mice were first infected with a non-lethal dose of influenza virus A (H/HK×31). Mice were then ovalbumin (OVA) sensitized during the acute-infection (3-days post inoculation) and then chronically underwent challenge to the airways with OVA. Forty-eight hours after the final OVA-challenge, airway hyperresponsiveness (AHR), bronchoalveolar fluid (BALF) cellular and cytokine profile, antigen-specific IgE and IgG1, and lung tissue inflammation were measured. Results Age-specific differences were noted on the effect of a viral infection, allergic sensitization, airway inflammation and airway hyperresponsiveness. Serum OVA-specific IgE was significantly increased in only the aged mice infected with influenza virus. Despite greater morbidity (e.g. weight loss and sickness scores) during the acute infection in the 18-month old mice that were OVA-sensitized there was little effect on the AHR and BALF cellular differential. In contrast, BALF neutrophils and AHR increased, but eosinophils decreased in 6-week mice that were OVA-sensitized during an acute influenza infection. Conclusion With increased age in a mouse model, viral infection prior to antigen sensitization affects the airway and systemic allergic response differently. These differences may reflect distinct phenotypic features of allergic inflammation in older patients with asthma PMID:25039815

  2. Hyperoxia promotes polarization of the immune response in ovalbumin-induced airway inflammation, leading to a TH17 cell phenotype

    PubMed Central

    Nagato, Akinori C; Bezerra, Frank S; Talvani, André; Aarestrup, Beatriz J; Aarestrup, Fernando M

    2015-01-01

    Previous studies have demonstrated that hyperoxia-induced stress and oxidative damage to the lungs of mice lead to an increase in IL-6, TNF-α, and TGF-β expression. Together, IL-6 and TGF-β have been known to direct T cell differentiation toward the TH17 phenotype. In the current study, we tested the hypothesis that hyperoxia promotes the polarization of T cells to the TH17 cell phenotype in response to ovalbumin-induced acute airway inflammation. Airway inflammation was induced in female BALB/c mice by intraperitoneal sensitization and intranasal introduction of ovalbumin, followed by challenge methacholine. After the methacholine challenge, animals were exposed to hyperoxic conditions in an inhalation chamber for 24 h. The controls were subjected to normoxia or aluminum hydroxide dissolved in phosphate buffered saline. After 24 h of hyperoxia, the number of macrophages and lymphocytes decreased in animals with ovalbumin-induced airway inflammation, whereas the number of neutrophils increased after ovalbumin-induced airway inflammation. The results showed that expression of Nrf2, iNOS, T-bet and IL-17 increased after 24 of hyperoxia in both alveolar macrophages and in lung epithelial cells, compared with both animals that remained in room air, and animals with ovalbumin-induced airway inflammation. Hyperoxia alone without the induction of airway inflammation lead to increased levels of TNF-α and CCL5, whereas hyperoxia after inflammation lead to decreased CCL2 levels. Histological evidence of extravasation of inflammatory cells into the perivascular and peribronchial regions of the lungs was observed after pulmonary inflammation and hyperoxia. Hyperoxia promotes polarization of the immune response toward the TH17 phenotype, resulting in tissue damage associated with oxidative stress, and the migration of neutrophils to the lung and airways. Elucidating the effect of hyperoxia on ovalbumin-induced acute airway inflammation is relevant to preventing or

  3. The role of the epithelium in airway remodeling in asthma.

    PubMed

    Davies, Donna E

    2009-12-01

    The bronchial epithelium is the barrier to the external environment and plays a vital role in protection of the internal milieu of the lung. It functions within the epithelial-mesenchymal trophic unit to control the local microenvironment and help maintain tissue homeostasis. However, in asthma, chronic perturbation of these homeostatic mechanisms leads to alterations in the structure of the airways, termed remodeling. Damage to the epithelium is now recognized to play a key role in driving airway remodeling. We have postulated that epithelial susceptibility to environmental stress and injury together with impaired repair responses results in generation of signals that act on the underlying mesenchyme to propagate and amplify inflammatory and remodeling responses in the submucosa. Many types of challenges to the epithelium, including pathogens, allergens, environmental pollutants, cigarette smoke, and even mechanical forces, can elicit production of mediators by the epithelium, which can be translated into remodeling responses by the mesenchyme. Several important mediators of remodeling have been identified, most notably transforming growth factor-beta, which is released from damaged/repairing epithelium or in response to inflammatory mediators, such as IL-13. The cross talk between the epithelium and the underlying mesenchyme to drive remodeling responses is considered in the context of subepithelial fibrosis and potential pathogenetic mechanisms linked to the asthma susceptibility gene, a disintegrin and metalloprotease (ADAM)33. PMID:20008875

  4. Pulmonary CD103 expression regulates airway inflammation in asthma.

    PubMed

    Bernatchez, Emilie; Gold, Matthew J; Langlois, Anick; Lemay, Anne-Marie; Brassard, Julyanne; Flamand, Nicolas; Marsolais, David; McNagny, Kelly M; Blanchet, Marie-Renee

    2015-04-15

    Although CD103(+) cells recently emerged as key regulatory cells in the gut, the role of CD103 ubiquitous expression in the lung and development of allergic airway disease has never been studied. To answer this important question, we evaluated the response of Cd103(-/-) mice in two separate well-described mouse models of asthma (ovalbumin and house dust mite extract). Pulmonary inflammation was assessed by analysis of bronchoalveolar lavage content, histology, and cytokine response. CD103 expression was analyzed on lung dendritic cells and T cell subsets by flow cytometry. Cd103(-/-) mice exposed to antigens developed exacerbated lung inflammation, characterized by increased eosinophilic infiltration, severe tissue inflammation, and altered cytokine response. In wild-type mice exposed to house dust mite, CD103(+) dendritic cells are increased in the lung and an important subset of CD4(+) T cells, CD8(+) T cells, and T regulatory cells express CD103. Importantly, Cd103(-/-) mice presented a deficiency in the resolution phase of inflammation, which supports an important role for this molecule in the control of inflammation severity. These results suggest an important role for CD103 in the control of airway inflammation in asthma. PMID:25681437

  5. The PPARγ agonist, rosiglitazone, attenuates airway inflammation and remodeling via heme oxygenase-1 in murine model of asthma

    PubMed Central

    Xu, Jing; Zhu, Yan-ting; Wang, Gui-zuo; Han, Dong; Wu, Yuan-yuan; Zhang, De-xin; Liu, Yun; Zhang, Yong-hong; Xie, Xin-ming; Li, Shao-jun; Lu, Jia-mei; Liu, Lu; Feng, Wei; Sun, Xiu-zhen; Li, Man-xiang

    2015-01-01

    Aim: Rosiglitazone is one of the specific PPARγ agonists showing potential therapeutic effects in asthma. Though PPARγ activation was considered protective in inhibiting airway inflammation and remodeling in asthma, the specific mechanisms are still unclear. This study was aimed to investigate whether heme oxygenase-1 (HO-1) related pathways were involved in rosiglitazone-activated PPARγ signaling in asthma treatment. Methods: Asthma was induced in mice by multiple exposures to ovalbumin (OVA) in 8 weeks. Prior to every OVA challenge, the mice received rosiglitazone (5 mg/kg, po). After the mice were sacrificed, the bronchoalveolar lavage fluid (BALF), blood samples and lungs were collected for analyses. The activities of HO-1, MMP-2 and MMP-9 in airway tissue were assessed, and the expression of PPARγ, HO-1 and p21 proteins was also examined. Results: Rosiglitazone administration significantly attenuated airway inflammation and remodeling in mice with OVA-induced asthma, which were evidenced by decreased counts of total cells, eosinophils and neutrophils, and decreased levels of IL-5 and IL-13 in BALF, and by decreased airway smooth muscle layer thickness and reduced airway collagen deposition. Furthermore, rosiglitazone administration significantly increased PPARγ, HO-1 and p21 expression and HO-1 activity, decreased MMP-2 and MMP-9 activities in airway tissue. All the therapeutic effects of rosiglitazone were significantly impaired by co-administration of the HO-1 inhibitor ZnPP. Conclusion: Rosiglitazone effectively attenuates airway inflammation and remodeling in OVA- induced asthma of mice by activating PPARγ/HO-1 signaling pathway. PMID:25619395

  6. Drug Eluting Stents for Malignant Airway Obstruction: A Critical Review of the Literature

    PubMed Central

    Hohenforst-Schmidt, Wolfgang; Zarogoulidis, Paul; Pitsiou, Georgia; Linsmeier, Bernd; Tsavlis, Drosos; Kioumis, Ioannis; Papadaki, Eleni; Freitag, Lutz; Tsiouda, Theodora; Turner, J Francis; Browning, Robert; Simoff, Michael; Sachpekidis, Nikolaos; Tsakiridis, Kosmas; Zaric, Bojan; Yarmus, Lonny; Baka, Sofia; Stratakos, Grigoris; Rittger, Harald

    2016-01-01

    Lung cancer being the most prevalent malignancy in men and the 3rd most frequent in women is still associated with dismal prognosis due to advanced disease at the time of diagnosis. Novel targeted therapies are already on the market and several others are under investigation. However non-specific cytotoxic agents still remain the cornerstone of treatment for many patients. Central airways stenosis or obstruction may often complicate and decrease quality of life and survival of these patients. Interventional pulmonology modalities (mainly debulking and stent placement) can alleviate symptoms related to airways stenosis and improve the quality of life of patients. Mitomycin C and sirolimus have been observed to assist a successful stent placement by reducing granuloma tissue formation. Additionally, these drugs enhance the normal tissue ability against cancer cell infiltration. In this mini review we will concentrate on mitomycin C and sirolimus and their use in stent placement. PMID:26918052

  7. 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.

  8. The innate immune function of airway epithelial cells in inflammatory lung disease.

    PubMed

    Hiemstra, Pieter S; McCray, Paul B; Bals, Robert

    2015-04-01

    The airway epithelium is now considered to be central to the orchestration of pulmonary inflammatory and immune responses, and is also key to tissue remodelling. It acts as the first barrier in the defence against a wide range of inhaled challenges, and is critically involved in the regulation of both innate and adaptive immune responses to these challenges. Recent progress in our understanding of the developmental regulation of this tissue, the differentiation pathways, recognition of pathogens and antimicrobial responses is now exploited to help understand how epithelial cell function and dysfunction contributes to the pathogenesis of a variety of inflammatory lung diseases. Herein, advances in our knowledge of the biology of airway epithelium, as well as its role and (dys)function in asthma, chronic obstructive pulmonary fibrosis and cystic fibrosis will be discussed. PMID:25700381

  9. The innate immune function of airway epithelial cells in inflammatory lung disease

    PubMed Central

    Hiemstra, Pieter S.; McCray, Paul B.; Bals, Robert

    2016-01-01

    The airway epithelium is now considered central to the orchestration of pulmonary inflammatory and immune responses, and is also key to tissue remodelling. It acts as a first barrier in the defence against a wide range of inhaled challenges, and is critically involved in the regulation of both innate and adaptive immune responses to these challenges. Recent progress in our understanding of the developmental regulation of this tissue, the differentiation pathways, recognition of pathogens and antimicrobial responses is now exploited to help understand how epithelial cell function and dysfunction contributes to the pathogenesis of a variety of inflammatory lung diseases. In the review, advances in our knowledge of the biology of airway epithelium, as well as its role and (dys)function in asthma, COPD and cystic fibrosis, are discussed. PMID:25700381

  10. 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.

  11. 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

  12. 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

  13. Cigarette smoke makes airway and early parenchymal asbestos-induced lung disease worse in the guinea pig

    SciTech Connect

    Tron, V.; Wright, J.L.; Harrison, N.; Wiggs, B.; Churg, A.

    1987-08-01

    In order to assess the effects of cigarette smoke and asbestos exposure, we divided guinea pigs into 4 groups: smoking or nonsmoking, and asbestos-exposed or not asbestos-exposed groups. Asbestos-exposed animals were given a single intratracheal instillation of 5 mg UICC amosite, a dose and method of administration that we have previously shown produces morphologic changes in the small airways as well as minimal interstitial fibrosis. Animals were smoked 5 days per week for 6 months. By itself, smoking did not affect lung collagen content, small airways wall thickness, or the volume fraction of tissue surrounding airways, but it did cause a significant increase in alveolar mean linear intercept (Lm). Asbestos alone increased collagen content, airway wall thickness, and tissue volume fraction surrounding airways, the latter measure used to assess interstitial fibrosis. An unexpected finding was that asbestos also increased Lm. The two agents administered together caused more severe changes of all types than were produced by either agent alone, and the interaction between the 2 was generally synergistic. Smoke-exposed animals retained 3 times the asbestos fiber burden of those not smoke-exposed; the increase in retention was greater for short than for long fibers. We conclude that cigarette smoke can potentiate the fibrosis induced by asbestos, possibly because of increased fiber retention. As well, in this model, asbestos or asbestos plus cigarette smoke produces increases in alveolar size.

  14. Neutrophil extracellular traps cause airway obstruction during respiratory syncytial virus disease.

    PubMed

    Cortjens, Bart; de Boer, Onno J; de Jong, Rineke; Antonis, Adriaan Fg; Sabogal Piñeros, Yanaika S; Lutter, René; van Woensel, Job Bm; Bem, Reinout A

    2016-02-01

    Human respiratory syncytial virus (RSV) is the most important cause of severe lower respiratory tract disease (LRTD) in young children worldwide. Extensive neutrophil accumulation in the lungs and occlusion of small airways by DNA-rich mucus plugs are characteristic features of severe RSV-LRTD. Activated neutrophils can release neutrophil extracellular traps (NETs), extracellular networks of DNA covered with antimicrobial proteins, as part of the first-line defence against pathogens. NETs can trap and eliminate microbes; however, abundant NET formation may also contribute to airway occlusion. In this study, we investigated whether NETs are induced by RSV and explored their potential anti-viral effect in vitro. Second, we studied NET formation in vivo during severe RSV-LRTD in infants and bovine RSV-LRTD in calves, by examining bronchoalveolar lavage fluid and lung tissue sections, respectively. NETs were visualized in lung cytology and tissue samples by DNA and immunostaining, using antibodies against citrullinated histone H3, elastase and myeloperoxidase. RSV was able to induce NET formation by human neutrophils in vitro. Furthermore, NETs were able to capture RSV, thereby precluding binding of viral particles to target cells and preventing infection. Evidence for the formation of NETs in the airways and lungs was confirmed in children with severe RSV-LRTD. Detailed histopathological examination of calves with RSV-LRTD showed extensive NET formation in dense plugs occluding the airways, either with or without captured viral antigen. Together, these results suggest that, although NETs trap viral particles, their exaggerated formation during severe RSV-LRTD contributes to airway obstruction. PMID:26468056

  15. A Multi-Scale Approach to Airway Hyperresponsiveness: From Molecule to Organ

    PubMed Central

    Lauzon, Anne-Marie; Bates, Jason H. T.; Donovan, Graham; Tawhai, Merryn; Sneyd, James; Sanderson, Michael J.

    2012-01-01

    Airway hyperresponsiveness (AHR), a characteristic of asthma that involves an excessive reduction in airway caliber, is a complex mechanism reflecting multiple processes that manifest over a large range of length and time scales. At one extreme, molecular interactions determine the force generated by airway smooth muscle (ASM). At the other, the spatially distributed constriction of the branching airways leads to breathing difficulties. Similarly, asthma therapies act at the molecular scale while clinical outcomes are determined by lung function. These extremes are linked by events operating over intermediate scales of length and time. Thus, AHR is an emergent phenomenon that limits our understanding of asthma and confounds the interpretation of studies that address physiological mechanisms over a limited range of scales. A solution is a modular computational model that integrates experimental and mathematical data from multiple scales. This includes, at the molecular scale, kinetics, and force production of actin-myosin contractile proteins during cross-bridge and latch-state cycling; at the cellular scale, Ca2+ signaling mechanisms that regulate ASM force production; at the tissue scale, forces acting between contracting ASM and opposing viscoelastic tissue that determine airway narrowing; at the organ scale, the topographic distribution of ASM contraction dynamics that determine mechanical impedance of the lung. At each scale, models are constructed with iterations between theory and experimentation to identify the parameters that link adjacent scales. This modular model establishes algorithms for modeling over a wide range of scales and provides a framework for the inclusion of other responses such as inflammation or therapeutic regimes. The goal is to develop this lung model so that it can make predictions about bronchoconstriction and identify the pathophysiologic mechanisms having the greatest impact on AHR and its therapy. PMID:22701430

  16. Near Equilibrium Calculus of Stem Cells in Application to the Airway Epithelium Lineage.

    PubMed

    Sun, Zheng; Plikus, Maksim V; Komarova, Natalia L

    2016-07-01

    Homeostatic maintenance of tissues is orchestrated by well tuned networks of cellular signaling. Such networks regulate, in a stochastic manner, fates of all cells within the respective lineages. Processes such as symmetric and asymmetric divisions, differentiation, de-differentiation, and death have to be controlled in a dynamic fashion, such that the cell population is maintained at a stable equilibrium, has a sufficiently low level of stochastic variation, and is capable of responding efficiently to external damage. Cellular lineages in real tissues may consist of a number of different cell types, connected by hierarchical relationships, albeit not necessarily linear, and engaged in a number of different processes. Here we develop a general mathematical methodology for near equilibrium studies of arbitrarily complex hierarchical cell populations, under regulation by a control network. This methodology allows us to (1) determine stability properties of the network, (2) calculate the stochastic variance, and (3) predict how different control mechanisms affect stability and robustness of the system. We demonstrate the versatility of this tool by using the example of the airway epithelium lineage. Recent research shows that airway epithelium stem cells divide mostly asymmetrically, while the so-called secretory cells divide predominantly symmetrically. It further provides quantitative data on the recovery dynamics of the airway epithelium, which can include secretory cell de-differentiation. Using our new methodology, we demonstrate that while a number of regulatory networks can be compatible with the observed recovery behavior, the observed division patterns of cells are the most optimal from the viewpoint of homeostatic lineage stability and minimizing the variation of the cell population size. This not only explains the observed yet poorly understood features of airway tissue architecture, but also helps to deduce the information on the still largely hypothetical

  17. Near Equilibrium Calculus of Stem Cells in Application to the Airway Epithelium Lineage

    PubMed Central

    Sun, Zheng; Plikus, Maksim V.; Komarova, Natalia L.

    2016-01-01

    Homeostatic maintenance of tissues is orchestrated by well tuned networks of cellular signaling. Such networks regulate, in a stochastic manner, fates of all cells within the respective lineages. Processes such as symmetric and asymmetric divisions, differentiation, de-differentiation, and death have to be controlled in a dynamic fashion, such that the cell population is maintained at a stable equilibrium, has a sufficiently low level of stochastic variation, and is capable of responding efficiently to external damage. Cellular lineages in real tissues may consist of a number of different cell types, connected by hierarchical relationships, albeit not necessarily linear, and engaged in a number of different processes. Here we develop a general mathematical methodology for near equilibrium studies of arbitrarily complex hierarchical cell populations, under regulation by a control network. This methodology allows us to (1) determine stability properties of the network, (2) calculate the stochastic variance, and (3) predict how different control mechanisms affect stability and robustness of the system. We demonstrate the versatility of this tool by using the example of the airway epithelium lineage. Recent research shows that airway epithelium stem cells divide mostly asymmetrically, while the so-called secretory cells divide predominantly symmetrically. It further provides quantitative data on the recovery dynamics of the airway epithelium, which can include secretory cell de-differentiation. Using our new methodology, we demonstrate that while a number of regulatory networks can be compatible with the observed recovery behavior, the observed division patterns of cells are the most optimal from the viewpoint of homeostatic lineage stability and minimizing the variation of the cell population size. This not only explains the observed yet poorly understood features of airway tissue architecture, but also helps to deduce the information on the still largely hypothetical

  18. Airway compliance and dynamics explain the apparent discrepancy in length adaptation between intact airways and smooth muscle strips.

    PubMed

    Dowie, Jackson; Ansell, Thomas K; Noble, Peter B; Donovan, Graham M

    2016-01-01

    Length adaptation is a phenomenon observed in airway smooth muscle (ASM) wherein over time there is a shift in the length-tension curve. There is potential for length adaptation to play an important role in airway constriction and airway hyper-responsiveness in asthma. Recent results by Ansell et al., 2015 (JAP 2014 10.1152/japplphysiol.00724.2014) have cast doubt on this role by testing for length adaptation using an intact airway preparation, rather than strips of ASM. Using this technique they found no evidence for length adaptation in intact airways. Here we attempt to resolve this apparent discrepancy by constructing a minimal mathematical model of the intact airway, including ASM which follows the classic length-tension curve and undergoes length adaptation. This allows us to show that (1) no evidence of length adaptation should be expected in large, cartilaginous, intact airways; (2) even in highly compliant peripheral airways, or at more compliant regions of the pressure-volume curve of large airways, the effect of length adaptation would be modest and at best marginally detectable in intact airways; (3) the key parameters which control the appearance of length adaptation in intact airways are airway compliance and the relaxation timescale. The results of this mathematical simulation suggest that length adaptation observed at the level of the isolated ASM may not clearly manifest in the normal intact airway. PMID:26376002

  19. Prenatal detection of congenital high airway obstruction syndrome with encephalocele

    PubMed Central

    Padmanabhan, Laxmi Devi; Nampoothiri, Sheela

    2016-01-01

    Congenital high airway obstruction syndrome (CHAOS) causes secondary morphological changes which can be detected on ultrasound. Here we report a case of congenital high airway obstruction with an occipital encephalocele detected at 23 weeks of gestation. PMID:27081227

  20. SPONTANEOUS AIRWAY HYPERRESPONSIVENESS IN ESTROGEN RECEPTOR-A DEFICIENT MICE

    EPA Science Inventory

    Rationale: Airway hyperresponsiveness is a critical feature of asthma. Substantial epidemiologic evidence supports a role for female sex hormones in modulating lung function and airway hyperresponsiveness in humans. Objectives: To examine the role of estrogen receptors in modulat...

  1. Markers of airway inflammation and airway hyperresponsiveness in patients with well-controlled asthma.

    PubMed

    Leuppi, J D; Salome, C M; Jenkins, C R; Koskela, H; Brannan, J D; Anderson, S D; Andersson, M; Chan, H K; Woolcock, A J

    2001-09-01

    In steroid-naive asthmatics, airway hyperresponsiveness correlates with noninvasive markers of airway inflammation. Whether this is also true in steroid-treated asthmatics, is unknown. In 31 stable asthmatics (mean age 45.4 yrs, range 22-69; 17 females) taking a median dose of 1,000 microg inhaled corticosteroids (ICS) per day (range 100-3,600 microg x day(-1)), airway responsiveness to the "direct" agent histamine and to the "indirect" agent mannitol, lung function (forced expiratory volume in one second (FEV1), forced vital capacity (FVC), peak expiratory flow (PEF)), exhaled nitric oxide (eNO), and number of inflammatory cells in induced sputum as a percentage of total cell count were measured. Of the 31 subjects, 16 were hyperresponsive to mannitol and 11 to histamine. The dose-response ratio (DRR: % fall in FEV1/cumulative dose) to both challenge tests was correlated (r=0.59, p=0.0004). However, DRR for histamine and DRR for mannitol were not related to basic lung function, eNO, per cent sputum eosinophils and ICS dose. In addition, NO was not related to basic lung function and per cent sputum eosinophils. In clinically well-controlled asthmatics taking inhaled corticosteroids, there is no relationship between markers of airway inflammation (such as exhaled nitric oxide and sputum eosinophils) and airway responsiveness to either direct (histamine) or indirect (mannitol) challenge. Airway hyperresponsiveness in clinically well-controlled asthmatics appears to be independent of eosinophilic airway inflammation. PMID:11589340

  2. 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

  3. 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

  4. EGF shifts human airway basal cell fate toward a smoking-associated airway epithelial phenotype.

    PubMed

    Shaykhiev, Renat; Zuo, Wu-Lin; Chao, Ionwa; Fukui, Tomoya; Witover, Bradley; Brekman, Angelika; Crystal, Ronald G

    2013-07-16

    The airway epithelium of smokers acquires pathological phenotypes, including basal cell (BC) and/or goblet cell hyperplasia, squamous metaplasia, structural and functional abnormalities of ciliated cells, decreased number of secretoglobin (SCGB1A1)-expressing secretory cells, and a disordered junctional barrier. In this study, we hypothesized that smoking alters airway epithelial structure through modification of BC function via an EGF receptor (EGFR)-mediated mechanism. Analysis of the airway epithelium revealed that EGFR is enriched in airway BCs, whereas its ligand EGF is induced by smoking in ciliated cells. Exposure of BCs to EGF shifted the BC differentiation program toward the squamous and epithelial-mesenchymal transition-like phenotypes with down-regulation of genes related to ciliogenesis, secretory differentiation, and markedly reduced junctional barrier integrity, mimicking the abnormalities present in the airways of smokers in vivo. These data suggest that activation of EGFR in airway BCs by smoking-induced EGF represents a unique mechanism whereby smoking can alter airway epithelial differentiation and barrier function. PMID:23818594

  5. 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

  6. MicroRNA in United Airway Diseases

    PubMed Central

    Liu, Zheng; Zhang, Xin-Hao; Callejas-Díaz, Borja; Mullol, Joaquim

    2016-01-01

    The concept of united airway diseases (UAD) has received increasing attention in recent years. Sustained and increased inflammation is a common feature of UAD, which is inevitably accompanied with marked gene modification and tight gene regulation. However, gene regulation in the common inflammatory processes in UAD remains unclear. MicroRNA (miRNA), a novel regulator of gene expression, has been considered to be involved in many inflammatory diseases. Although there are an increasing number of studies of miRNAs in inflammatory upper and lower airway diseases, few miRNAs have been identified that directly link the upper and lower airways. In this article, therefore, we reviewed the relevant studies available in order to improve the understanding of the roles of miRNAs in the interaction and pathogenesis of UAD. PMID:27187364

  7. MicroRNA in United Airway Diseases.

    PubMed

    Liu, Zheng; Zhang, Xin-Hao; Callejas-Díaz, Borja; Mullol, Joaquim

    2016-01-01

    The concept of united airway diseases (UAD) has received increasing attention in recent years. Sustained and increased inflammation is a common feature of UAD, which is inevitably accompanied with marked gene modification and tight gene regulation. However, gene regulation in the common inflammatory processes in UAD remains unclear. MicroRNA (miRNA), a novel regulator of gene expression, has been considered to be involved in many inflammatory diseases. Although there are an increasing number of studies of miRNAs in inflammatory upper and lower airway diseases, few miRNAs have been identified that directly link the upper and lower airways. In this article, therefore, we reviewed the relevant studies available in order to improve the understanding of the roles of miRNAs in the interaction and pathogenesis of UAD. PMID:27187364

  8. Innate lymphoid cells in the airways.

    PubMed

    Walker, Jennifer A; McKenzie, Andrew

    2012-06-01

    The airways, similar to other mucosal surfaces, are continuously exposed to the outside environment and a barrage of antigens, allergens, and microorganisms. Of critical importance therefore is the ability to mount rapid and effective immune responses to control commensal and pathogenic microbes, while simultaneously limiting the extent of these responses to prevent immune pathology and chronic inflammation. The function of the adaptive immune response in controlling these processes at mucosal surfaces has been well documented but the important role of the innate immune system, particularly the recently identified family of innate lymphoid cells, has only lately become apparent. In this review, we give an overview of the innate lymphoid cells that exist in the airways and examine the evidence pertaining to their emerging roles in airways immunity, inflammation, and homeostasis. PMID:22678892

  9. Use of continuous positive airway pressure reduces airway reactivity in adults with asthma

    PubMed Central

    Busk, Michael; Busk, Nancy; Puntenney, Paula; Hutchins, Janet; Yu, Zhangsheng; Gunst, Susan J.; Tepper, Robert S.

    2015-01-01

    Asthma is characterised by airway hyperreactivity, which is primarily treated with β-adrenergic bronchodilators and anti-inflammatory agents. However, mechanical strain during breathing is an important modulator of airway responsiveness and we have previously demonstrated in animal models that continuous positive airway pressure (CPAP) resulted in lower in vivo airway reactivity. We now evaluated whether using nocturnal CPAP decreased airway reactivity in clinically-stable adults with asthma. Adults with stable asthma and normal spirometry used nocturnal CPAP (8–10 cmH2O) or sham treatment (0–2 cmH2O) for 7 days. Spirometry and bronchial challenges were obtained before and after treatment. The primary outcome was the provocative concentration of methacholine causing a 20% fall in forced expiratory volume in 1 s (PC20). The CPAP group (n=16) had a significant decrease in airway reactivity (change in (Δ)logPC20 0.406, p<0.0017) while the sham group (n=9) had no significant change in airway reactivity (ΔlogPC20 0.003, p=0.9850). There was a significant difference in the change in airway reactivity for the CPAP versus the sham group (ΔlogPC20 0.41, p<0.043). Our findings indicate that chronic mechanical strain of the lungs produced using nocturnal CPAP for 7 days reduced airway reactivity in clinically stable asthmatics. Future studies of longer duration are required to determine whether CPAP can also decrease asthma symptoms and/or medication usage. PMID:22835615

  10. Engineered silica nanoparticles act as adjuvants to enhance allergic airway disease in mice

    PubMed Central

    2013-01-01

    Background With the increase in production and use of engineered nanoparticles (NP; ≤ 100 nm), safety concerns have risen about the potential health effects of occupational or environmental NP exposure. Results of animal toxicology studies suggest that inhalation of NP may cause pulmonary injury with subsequent acute or chronic inflammation. People with chronic respiratory diseases like asthma or allergic rhinitis may be even more susceptible to toxic effects of inhaled NP. Few studies, however, have investigated adverse effects of inhaled NP that may enhance the development of allergic airway disease. Methods We investigated the potential of polyethylene glycol coated amorphous silica NP (SNP; 90 nm diameter) to promote allergic airway disease when co-exposed during sensitization with an allergen. BALB/c mice were sensitized by intranasal instillation with 0.02% ovalbumin (OVA; allergen) or saline (control), and co-exposed to 0, 10, 100, or 400 μg of SNP. OVA-sensitized mice were then challenged intranasally with 0.5% OVA 14 and 15 days after sensitization, and all animals were sacrificed a day after the last OVA challenge. Blood and bronchoalveolar lavage fluid (BALF) were collected, and pulmonary tissue was processed for histopathology and biochemical and molecular analyses. Results Co-exposure to SNP during OVA sensitization caused a dose-dependent enhancement of allergic airway disease upon challenge with OVA alone. This adjuvant-like effect was manifested by significantly greater OVA-specific serum IgE, airway eosinophil infiltration, mucous cell metaplasia, and Th2 and Th17 cytokine gene and protein expression, as compared to mice that were sensitized to OVA without SNP. In saline controls, SNP exposure did cause a moderate increase in airway neutrophils at the highest doses. Conclusions These results suggest that airway exposure to engineered SNP could enhance allergen sensitization and foster greater manifestation of allergic airway disease upon

  11. Pristimerin attenuates ovalbumin-induced allergic airway inflammation in mice.

    PubMed

    Jin, Yingli; Wang, Yujia; Zhao, Danning; Ma, Sitong; Lu, Jing; Shuang, Guan

    2016-06-01

    Pristimerin has been shown to possess antiinflammatory activity. However, its potential use for asthma induced by airway inflammation has not yet been studied. First, we established a ovalbumin (OVA)-induced allergic asthma mice model. BALB/c mice were immunized and challenged by OVA. Treatment with pristimerin caused a marked reduction in the levels of OVA-specific IgE, immune cells, and IL-4, IL-5, IL-13 secretion. Histological studies using H&E staining were used to study the alterations in lung tissue. These results were similar to those obtained with dexamethasone treatment. We then investigated which signal transduction mechanisms could be implicated in pristimerin activity by Western blot. The data showed that pristimerin could inhibit MAPKs and NF-κB inflammatory pathways. PMID:27098091

  12. Cardiac arrest due to airway obstruction in hereditary angioedema.

    PubMed

    Fuse, Takashi; Nakada, Taka-aki; Taniguchi, Masashi; Mizushima, Yasuaki; Matsuoka, Tetsuya

    2015-12-01

    Hereditary angioedema (HAE) is a rare genetic disease caused by a deficiency of functional C1 esterase inhibitor that causes swelling attacks in various body tissues. We hereby report a case of out-of-hospital cardiac arrest due to airway obstruction in HAE. Cutaneous swelling and abdominal pain attacks caused by gastrointestinal wall swelling are common symptoms in HAE, whereas laryngeal swelling is rare. Emergency physicians may have few chances to experience cases of life-threatening laryngeal edema resulting in a delay from symptom onset to the diagnosis of HAE. Hereditary angioedema is diagnosed by performing complement blood tests. Because safe and effective treatment options are available for the life-threatening swellings in HAE, the diagnosis potentially reduces the risk of asphyxiation in patients and their blood relatives. PMID:25913082

  13. Tension chylothorax complicating acute malignant airway obstruction.

    PubMed

    Piastra, Marco; Pietrini, Domenico; Ruggiero, Antonio; Rizzo, Daniela; Marzano, Laura; Attinà, Giorgio; De Luca, Daniele; De Rosa, Gabriella; Conti, Giorgio

    2011-05-01

    Acute upper airway obstruction represents one of the most challenging emergencies in pediatric practice. In particular, a tension chylothorax complicating a malignant airway obstruction is a rare and life-threatening complication. We report a rapidly progressing tension chylothorax associated with a cervical mass in a 10-month-old male infant. To our knowledge, the extension of a cervical mass to the supraclavear region resulting in a compressive chylothorax represents an exceptional event in pediatrics. Early recognition and prompt treatment resulted to be essential to relieve the compression and to avoid end-stage hemodynamic and respiratory function derangement. PMID:21546802

  14. Cine CT technique for dynamic airway studies

    SciTech Connect

    Ell, S.R.; Jolles, H.; Keyes, W.D.; Galvin, J.R.

    1985-07-01

    The advent of cine CT scanning with its 50-msec data acquisition time promises a much wider range of dynamic CT studies. The authors describe a method for dynamic evaluation of the extrathoracic airway, which they believe has considerable potential application in nonfixed upper-airway disease, such as sleep apnea and stridor of unknown cause. Conventional CT is limited in such studies by long data acquisition time and can be used to study only prolonged maneuvers such as phonation. Fluoroscopy and digital subtraction studies are limited by relatively high radiation dose and inability to image all wall motions simultaneously.

  15. 21 CFR 868.2600 - Airway pressure monitor.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Airway pressure monitor. 868.2600 Section 868.2600...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Monitoring Devices § 868.2600 Airway pressure monitor. (a) Identification. An airway pressure monitor is a device used to measure the pressure in a patient's upper...

  16. 21 CFR 868.1780 - Inspiratory airway pressure meter.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Inspiratory airway pressure meter. 868.1780... (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Diagnostic Devices § 868.1780 Inspiratory airway pressure meter. (a) Identification. An inspiratory airway pressure meter is a device used to measure the...

  17. 21 CFR 868.1780 - Inspiratory airway pressure meter.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Inspiratory airway pressure meter. 868.1780... (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Diagnostic Devices § 868.1780 Inspiratory airway pressure meter. (a) Identification. An inspiratory airway pressure meter is a device used to measure the...

  18. 21 CFR 868.1780 - Inspiratory airway pressure meter.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Inspiratory airway pressure meter. 868.1780... (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Diagnostic Devices § 868.1780 Inspiratory airway pressure meter. (a) Identification. An inspiratory airway pressure meter is a device used to measure the...

  19. 21 CFR 868.2600 - Airway pressure monitor.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Airway pressure monitor. 868.2600 Section 868.2600...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Monitoring Devices § 868.2600 Airway pressure monitor. (a) Identification. An airway pressure monitor is a device used to measure the pressure in a patient's upper...

  20. 21 CFR 868.2600 - Airway pressure monitor.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Airway pressure monitor. 868.2600 Section 868.2600...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Monitoring Devices § 868.2600 Airway pressure monitor. (a) Identification. An airway pressure monitor is a device used to measure the pressure in a patient's upper...

  1. 21 CFR 868.1780 - Inspiratory airway pressure meter.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Inspiratory airway pressure meter. 868.1780... (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Diagnostic Devices § 868.1780 Inspiratory airway pressure meter. (a) Identification. An inspiratory airway pressure meter is a device used to measure the...

  2. 21 CFR 868.2600 - Airway pressure monitor.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Airway pressure monitor. 868.2600 Section 868.2600...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Monitoring Devices § 868.2600 Airway pressure monitor. (a) Identification. An airway pressure monitor is a device used to measure the pressure in a patient's upper...

  3. 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

  4. Inhalation of chlorine causes long-standing lung inflammation and airway hyperresponsiveness in a murine model of chemical-induced lung injury.

    PubMed

    Jonasson, Sofia; Koch, Bo; Bucht, Anders

    2013-01-01

    Chlorine is highly irritating when inhaled, and is a common toxic industrial gas causing tissue damage in the airways followed by an acute inflammatory response. In this study, we investigated mechanisms by which chlorine exposure may cause reactive airways dysfunction syndrome (RADS) and we examined the dose-dependency of the development of symptoms. Mice were exposed to 50 or 200 ppm Cl(2) during a single 15 min exposure in a nose-only container. The experiment terminated 2, 6, 12, 24, 48, 72 h and 7, 14, 28 and 90 days post exposure. Inflammatory cell counts in bronchoalveolar lavage (BAL), secretion of inflammatory mediators in BAL, occurrence of lung edema and histopathological changes in lung tissue was analyzed at each time-point. Airway hyperresponsiveness (AHR) was studied after 24 and 48 h and 7, 14, 28 and 90 days. The results showed a marked acute response at 6h (50 ppm) and 12h (200 ppm) post exposure as indicated by induced lung edema, increased airway reactivity in both central and peripheral airways, and an airway inflammation dominated by macrophages and neutrophils. The inflammatory response declined rapidly in airways, being normalized after 48 h, but inflammatory cells were sustained in lung tissue for at least seven days. In addition, a sustained AHR was observed for at least 28 days. In summary, this mouse model of chlorine exposure shows delayed symptoms of hyperreactive airways similar to human RADS. We conclude that the model can be used for studies aimed at improved understanding of adverse long-term responses following inhalation of chlorine. PMID:23146759

  5. Increased Mast Cell Density and Airway Responses to Allergic and Non-Allergic Stimuli in a Sheep Model of Chronic Asthma

    PubMed Central

    Van der Velden, Joanne; Barker, Donna; Barcham, Garry; Koumoundouros, Emmanuel; Snibson, Kenneth

    2012-01-01

    Background Increased mast cell (MC) density and changes in their distribution in airway tissues is thought to contribute significantly to the pathophysiology of asthma. However, the time sequence for these changes and how they impact small airway function in asthma is not fully understood. The aim of the current study was to characterise temporal changes in airway MC density and correlate these changes with functional airway responses in sheep chronically challenged with house dust mite (HDM) allergen. Methodology/Principal Findings MC density was examined on lung tissue from four spatially separate lung segments of allergic sheep which received weekly challenges with HDM allergen for 0, 8, 16 or 24 weeks. Lung tissue was collected from each segment 7 days following the final challenge. The density of tryptase-positive and chymase-positive MCs (MCT and MCTC respectively) was assessed by morphometric analysis of airway sections immunohistochemically stained with antibodies against MC tryptase and chymase. MCT and MCTC density was increased in small bronchi following 24 weeks of HDM challenges compared with controls (P<0.05). The MCTC/MCT ratio was significantly increased in HDM challenged sheep compared to controls (P<0.05). MCT and MCTC density was inversely correlated with allergen-induced increases in peripheral airway resistance after 24 weeks of allergen exposure (P<0.05). MCT density was also negatively correlated with airway responsiveness after 24 challenges (P<0.01). Conclusions MCT and MCTC density in the small airways correlates with better lung function in this sheep model of chronic asthma. Whether this finding indicates that under some conditions mast cells have protective activities in asthma, or that other explanations are to be considered requires further investigation. PMID:22606346

  6. 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

  7. Murine Cytomegalovirus Influences Foxj1 Expression, Ciliogenesis, and Mucus Plugging in Mice with Allergic Airway Disease

    PubMed Central

    Wu, Carol A.; Peluso, John J.; Shanley, John D.; Puddington, Lynn; Thrall, Roger S.

    2008-01-01

    We have followed throughout time the development of allergic airway disease (AAD) in both uninfected mice and mice infected intranasally with murine cytomegalovirus (MCMV). Histological evaluation of lung tissue from uninfected mice with AAD demonstrated mucus plugging after 14 and 21 days of ovalbumin-aerosol challenge, with resolution of mucus plugging occurring by 42 days. In MCMV/AAD mice, mucus plugging was observed after 7 days of ovalbumin-aerosol challenge and remained present at 42 days. The level of interleukin-13 in bronchoalveolar lavage fluid from MCMV/AAD mice was decreased compared with AAD mice and was accompanied by increased levels of interferon-γ. Levels of Muc5A/C, Muc5B, or Muc2 mucin mRNA in the lungs of MCMV/AAD mice were not elevated compared with AAD mice. MCMV was able to infect the airway epithelium, resulting in decreased expression of Foxj1, a transcription factor critical for ciliogenesis, and a loss of ciliated epithelial cells. In addition, an increase in the number of epithelial cells staining positive for periodic acid-Schiff was observed in MCMV/AAD airways. Together, these findings suggest that MCMV infection of the airway epithelium enhances goblet cell metaplasia and diminishes efficient mucociliary clearance in mice with AAD, resulting in increased mucus plugging. PMID:18258850

  8. Creation and characterization of an airway epithelial cell line for stable expression of CFTR variants

    PubMed Central

    Gottschalk, Laura B.; Vecchio-Pagan, Briana; Sharma, Neeraj; Han, Sangwoo T.; Franca, Arianna; Wohler, Elizabeth S.; Batista, Denise A.S.; Goff, Loyal A.; Cutting, Garry R.

    2016-01-01

    Background Analysis of the functional consequences and treatment response of rare CFTR variants is challenging due to the limited availability of primary airways cells. Methods A Flp recombination target (FRT) site for stable expression of CFTR was incorporated into an immortalized CF bronchial epithelial cell line (CFBE41o−). CFTR cDNA was integrated into the FRT site. Expression was evaluated by western blotting and confocal microscopy and function measured by short circuit current. RNA sequencing was used to compare the transcriptional profile of the resulting CF8Flp cell line to primary cells and tissues. Results Functional CFTR was expressed from integrated cDNA at the FRT site of the CF8Flp cell line at levels comparable to that seen in native airway cells. CF8Flp cells expressing WT-CFTR have a stable transcriptome comparable to that of primary cultured airway epithelial cells, including genes that play key roles in CFTR pathways. Conclusion CF8Flp cells provide a viable substitute for primary CF airway cells for the analysis of CFTR variants in a native context. PMID:26694805

  9. Protease inhibitor reduces airway response and underlying inflammation in cockroach allergen-induced murine model.

    PubMed

    Saw, Sanjay; Arora, Naveen

    2015-04-01

    Protease(s) enhances airway inflammation and allergic cascade. In the present study, effect of a serine protease inhibitor was evaluated in mouse model of airway disease. Mice were sensitized with cockroach extract (CE) or Per a 10 and treated with 4-(2-aminoethyl) benzenesulfonyl fluoride hydrochloride (AEBSF) 1 h before or after challenge to measure airway response. Mice were euthanized to collect bronchoalveolar lavage fluid (BALF), blood, and lung to evaluate inflammation. AEBSF treatment significantly reduced the AHR in allergen-challenged mice in dose-dependent manner (p≤ 0.01). IgE (p≤0.05) and Th2 cytokines (p≤0.05) were significantly reduced in treated mice. AEBSF treatment lowered total cell (p≤0.05), eosinophil (p≤0.05), and neutrophil (p≤0.05) in BALF and lung tissue. Oxidative stress parameters were impaired on treatment in allergen-challenged mice (p≤0.05). AEBSF had therapeutic effect in allergen-induced airway resistance and underling inflammation and had potential for combination or as add-on therapy for respiratory diseases. PMID:25052477

  10. Gravity effects on upper airway area and lung volumes during parabolic flight.

    PubMed

    Beaumont, M; Fodil, R; Isabey, D; Lofaso, F; Touchard, D; Harf, A; Louis, B

    1998-05-01

    We measured upper airway caliber and lung volumes in six normal subjects in the sitting and supine positions during 20-s periods in normogravity, hypergravity [1.8 + head-to-foot acceleration (Gz)], and microgravity ( approximately 0 Gz) induced by parabolic flights. Airway caliber and lung volumes were inferred by the acoustic reflection method and inductance plethysmography, respectively. In subjects in the sitting position, an increase in gravity from 0 to 1. 8 +Gz was associated with increases in the calibers of the retrobasitongue and palatopharyngeal regions (+20 and +30%, respectively) and with a concomitant 0.5-liter increase in end-expiratory lung volume (functional residual capacity, FRC). In subjects in the supine position, no changes in the areas of these regions were observed, despite significant decreases in FRC from microgravity to normogravity (-0.6 liter) and from microgravity to hypergravity (-0.5 liter). Laryngeal narrowing also occurred in both positions (about -15%) when gravity increased from 0 to 1.8 +Gz. We concluded that variation in lung volume is insufficient to explain all upper airway caliber variation but that direct gravity effects on tissues surrounding the upper airway should be taken into account. PMID:9572811

  11. Theoretical and experimental basis for the development of a dynamic airway stent.

    PubMed

    Freitag, L; Eicker, R; Linz, B; Greschuchna, D

    1994-11-01

    Three major problems are currently associated with airway stents: mucostasis, formation of granulation tissue, and migration. We wanted to determine whether these problems could be solved by a different stent design. Based on theoretical considerations of an idealized trachea, we developed a dynamic bifurcation stent made of silicone which incorporates horseshoe-shaped steel struts. A flexible posterior membrane enables dynamic compression during cough, whilst the clasps maintain the airway lumen in the face of external compression. The design of the stent cast was based upon computed tomographic (CT)-scan studies of the central airways. Its complex shape provides a smoother distribution of pressure on the mucosa; thereby, lowering the stimulus for granulation formation. The bronchial limbs saddle on the carina, preventing displacement. The mechanical behaviours of the new stent and two commercially available stents were compared in an ex-vivo model, utilizing freshly excised tracheae and new visualization techniques. Dynamic (artificial coughs) and static loads (simulating tumour compression or pleural pressures) were applied on excised human tracheae with different stents. Our dynamic stent preserved effective compression of the posterior membrane in response to cough, and also provided lumen stability against extrinsic compression. In comparison, the two commercially available stents did not provide both functions equally well. In conclusion, our newly designed dynamic bifurcation stent shows characteristics which should prove useful in avoiding problems currently associated with airway stents. PMID:7875279

  12. Methyl Protodioscin from the Roots of Asparagus cochinchinensis Attenuates Airway Inflammation by Inhibiting Cytokine Production

    PubMed Central

    Lee, Ju Hee; Lim, Hun Jai; Lee, Chan Woo; Son, Kun-Ho; Son, Jong-Keun; Lee, Sang Kook; Kim, Hyun Pyo

    2015-01-01

    The present study was designed to find pharmacologically active compound against airway inflammation from the roots of Asparagus cochinchinensis. The 70% ethanol extract of the roots of A. cochinchinensis (ACE) was found to inhibit IL-6 production from IL-1β-treated lung epithelial cells (A549) and the major constituent, methyl protodioscin (MP), also strongly inhibited the production of IL-6, IL-8, and tumor necrosis factor- (TNF-) α from A549 cells at 10–100 μM. This downregulating effect of proinflammatory cytokine production was found to be mediated, at least in part, via inhibition of c-Jun N-terminal kinase (JNK) and c-Jun activation pathway. When examined on an in vivo model of airway inflammation in mice, lipopolysaccharide- (LPS-) induced acute lung injury, ACE, and MP significantly inhibited cell infiltration in the bronchoalveolar lavage fluid by the oral treatment at doses of 100–400 mg/kg and 30–60 mg/kg, respectively. MP also inhibited the production of proinflammatory cytokines such as IL-6, TNF-α, and IL-1β in lung tissue. All of these findings provide scientific evidence supporting the role of A. cochinchinensis as a herbal remedy in treating airway inflammation and also suggest a therapeutic value of MP on airway inflammatory disorders. PMID:26379748

  13. Soft TCPTP Agonism—Novel Target to Rescue Airway Epithelial Integrity by Exogenous Spermidine

    PubMed Central

    Ghisalberti, Carlo A.; Borzì, Rosa M.; Cetrullo, Silvia; Flamigni, Flavio; Cairo, Gaetano

    2016-01-01

    A reparative approach of disrupted epithelium in obstructive airway diseases, namely asthma and chronic obstructive pulmonary disease (COPD), may afford protection and long-lasting results compared to conventional therapies, e.g., corticosteroids or immunosuppressant drugs. Here, we propose the polyamine spermidine as a novel therapeutic agent in airways diseases, based on a recently identified mode of action: T-cell protein tyrosine phosphatase (TCPTP) agonism. It may include and surpass single-inhibitors of stress and secondary growth factor pathway signaling, i.e., the new medicinal chemistry in lung diseases. Enhanced polyamine biosynthesis has been charged with aggravating prognosis by competing for L-arginine at detriment of nitric oxide (NO) synthesis with bronchoconstrictive effects. Although excess spermine, a higher polyamine, is harmful to airways physiology, spermidine can pivot the cell homeostasis during stress conditions by the activation of TCPTP. In fact, the dephosphorylating activity of TCPTP inhibits the signaling cascade that leads to the expression of genes involved in detachment and epithelial-to-mesenchymal transition (EMT), and increases the expression of adhesion and tight junction proteins, thereby enhancing the barrier functionality in inflammation-prone tissues. Moreover, a further beneficial effect of spermidine may derive from its ability to promote autophagy, possibly in a TCPTP-dependent way. Since doses of spermidine in the micromolar range are sufficient to activate TCPTP, low amounts of spermidine administered in sustained release modality may provide an optimal pharmacologic profile for the treatment of obstructive airway diseases. PMID:27375482

  14. Soft TCPTP Agonism-Novel Target to Rescue Airway Epithelial Integrity by Exogenous Spermidine.

    PubMed

    Ghisalberti, Carlo A; Borzì, Rosa M; Cetrullo, Silvia; Flamigni, Flavio; Cairo, Gaetano

    2016-01-01

    A reparative approach of disrupted epithelium in obstructive airway diseases, namely asthma and chronic obstructive pulmonary disease (COPD), may afford protection and long-lasting results compared to conventional therapies, e.g., corticosteroids or immunosuppressant drugs. Here, we propose the polyamine spermidine as a novel therapeutic agent in airways diseases, based on a recently identified mode of action: T-cell protein tyrosine phosphatase (TCPTP) agonism. It may include and surpass single-inhibitors of stress and secondary growth factor pathway signaling, i.e., the new medicinal chemistry in lung diseases. Enhanced polyamine biosynthesis has been charged with aggravating prognosis by competing for L-arginine at detriment of nitric oxide (NO) synthesis with bronchoconstrictive effects. Although excess spermine, a higher polyamine, is harmful to airways physiology, spermidine can pivot the cell homeostasis during stress conditions by the activation of TCPTP. In fact, the dephosphorylating activity of TCPTP inhibits the signaling cascade that leads to the expression of genes involved in detachment and epithelial-to-mesenchymal transition (EMT), and increases the expression of adhesion and tight junction proteins, thereby enhancing the barrier functionality in inflammation-prone tissues. Moreover, a further beneficial effect of spermidine may derive from its ability to promote autophagy, possibly in a TCPTP-dependent way. Since doses of spermidine in the micromolar range are sufficient to activate TCPTP, low amounts of spermidine administered in sustained release modality may provide an optimal pharmacologic profile for the treatment of obstructive airway diseases. PMID:27375482

  15. Allergic rhinitis and asthma: inflammation in a one-airway condition

    PubMed Central

    Jeffery, Peter K; Haahtela, Tari

    2006-01-01

    Background Allergic rhinitis and asthma are conditions of airway inflammation that often coexist. Discussion In susceptible individuals, exposure of the nose and lungs to allergen elicits early phase and late phase responses. Contact with antigen by mast cells results in their degranulation, the release of selected mediators, and the subsequent recruitment of other inflammatory cell phenotypes. Additional proinflammatory mediators are released, including histamine, prostaglandins, cysteinyl leukotrienes, proteases, and a variety of cytokines, chemokines, and growth factors. Nasal biopsies in allergic rhinitis demonstrate accumulations of mast cells, eosinophils, and basophils in the epithelium and accumulations of eosinophils in the deeper subepithelium (that is, lamina propria). Examination of bronchial tissue, even in mild asthma, shows lymphocytic inflammation enriched by eosinophils. In severe asthma, the predominant pattern of inflammation changes, with increases in the numbers of neutrophils and, in many, an extension of the changes to involve smaller airways (that is, bronchioli). Structural alterations (that is, remodeling) of bronchi in mild asthma include epithelial fragility and thickening of its reticular basement membrane. With increasing severity of asthma there may be increases in airway smooth muscle mass, vascularity, interstitial collagen, and mucus-secreting glands. Remodeling in the nose is less extensive than that of the lower airways, but the epithelial reticular basement membrane may be slightly but significantly thickened. Conclusion Inflammation is a key feature of both allergic rhinitis and asthma. There are therefore potential benefits for application of anti-inflammatory strategies that target both these anatomic sites. PMID:17140423

  16. Ambient particulate matter induces an exacerbation of airway inflammation in experimental asthma: role of interleukin-33

    PubMed Central

    Shadie, A M; Herbert, C; Kumar, R K

    2014-01-01

    High levels of ambient environmental particulate matter (PM10 i.e. < 10 μm median aerodynamic diameter) have been linked to acute exacerbations of asthma. We examined the effects of delivering a single dose of Sydney PM10 by intranasal instillation to BALB/c mice that had been sensitized to ovalbumin and challenged repeatedly with a low (≈3 mg/m3) mass concentration of aerosolized ovalbumin for 4 weeks. Responses were compared to animals administered carbon black as a negative control, or a moderate (≈30 mg/m3) concentration of ovalbumin to simulate an allergen-induced acute exacerbation of airway inflammation. Delivery of PM10 to mice, in which experimental mild chronic asthma had previously been established, elicited characteristic features of enhanced allergic inflammation of the airways, including eosinophil and neutrophil recruitment, similar to that in the allergen-induced exacerbation. In parallel, there was increased expression of mRNA for interleukin (IL)-33 in airway tissues and an increased concentration of IL-33 in bronchoalveolar lavage fluid. Administration of a monoclonal neutralizing anti-mouse IL-33 antibody prior to delivery of particulates significantly suppressed the inflammatory response induced by Sydney PM10, as well as the levels of associated proinflammatory cytokines in lavage fluid. We conclude that IL-33 plays a key role in driving airway inflammation in this novel experimental model of an acute exacerbation of chronic allergic asthma induced by exposure to PM10. PMID:24730559

  17. Methyl Protodioscin from the Roots of Asparagus cochinchinensis Attenuates Airway Inflammation by Inhibiting Cytokine Production.

    PubMed

    Lee, Ju Hee; Lim, Hun Jai; Lee, Chan Woo; Son, Kun-Ho; Son, Jong-Keun; Lee, Sang Kook; Kim, Hyun Pyo

    2015-01-01

    The present study was designed to find pharmacologically active compound against airway inflammation from the roots of Asparagus cochinchinensis. The 70% ethanol extract of the roots of A. cochinchinensis (ACE) was found to inhibit IL-6 production from IL-1β-treated lung epithelial cells (A549) and the major constituent, methyl protodioscin (MP), also strongly inhibited the production of IL-6, IL-8, and tumor necrosis factor- (TNF-) α from A549 cells at 10-100 μM. This downregulating effect of proinflammatory cytokine production was found to be mediated, at least in part, via inhibition of c-Jun N-terminal kinase (JNK) and c-Jun activation pathway. When examined on an in vivo model of airway inflammation in mice, lipopolysaccharide- (LPS-) induced acute lung injury, ACE, and MP significantly inhibited cell infiltration in the bronchoalveolar lavage fluid by the oral treatment at doses of 100-400 mg/kg and 30-60 mg/kg, respectively. MP also inhibited the production of proinflammatory cytokines such as IL-6, TNF-α, and IL-1β in lung tissue. All of these findings provide scientific evidence supporting the role of A. cochinchinensis as a herbal remedy in treating airway inflammation and also suggest a therapeutic value of MP on airway inflammatory disorders. PMID:26379748

  18. Antifibrinolytic Mechanisms in Acute Airway Injury after Sulfur Mustard Analog Inhalation

    PubMed Central

    Ahmad, Aftab; Veress, Livia A.; Rioux, Jacqueline S.; Garlick, Rhonda B.; White, Carl W.

    2014-01-01

    Acute lung injury in response to mustard gas (sulfur mustard [SM]) inhalation results in formation of fibrin casts, which obstruct the airway. The objective of this study was to identify fibrinolytic pathways that could be contributing to the persistence of airway casts after SM exposure. Rats were exposed to the SM analog, 2-chloroethyl ethyl sulfide, via nose-only aerosol inhalation. At 4 and 18 hours after exposure, animals were killed and airway–capillary leak estimated by measuring bronchoalveolar lavage fluid (BALF) protein and IgM content. The fibrin clot–degrading and plasminogen-activating capabilities of BALF were also assessed by activity assays, whereas Western blotting was used to determine the presence and activities of plasminogen activator inhibitor-1, thrombin activatable fibrinolytic inhibitor and α2-antiplasmin. Measurement of tissue-specific steady-state mRNA levels was also conducted for each fibrinolytic inhibitor to assess whether its synthesis occurs in lung or at extrapulmonary sites. The results of this study demonstrate that fibrin-degrading and plasminogen-activating capabilities of the airways become impaired during the onset of 2-chloroethyl ethyl sulfide–induced vascular leak. Findings of functionally active reservoirs of plasminogen activator inhibitor-1, thrombin activatable fibrinolysis inhibitor, and α2-antiplasmin in BALF indicate that airway fibrinolysis is inhibited at multiple levels in response to SM. PMID:24796565

  19. 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.

  20. Effects of concentrated ambient particles on normal and hypersecretory airways in rats.

    PubMed

    Harkema, Jack R; Keeler, Gerald; Wagner, James; Morishita, Masako; Timm, Edward; Hotchkiss, Jon; Marsik, Frank; Dvonch, Timothy; Kaminski, Norbert; Barr, Edward

    2004-08-01

    airway mucosubstances and pulmonary inflammation compared to saline-challenged/air-exposed control rats. OVA-challenged BN rats that were repeatedly exposed to CAPs in July 2000 had only minor CAPs-related effects. In only the September 5-day exposure protocol, PM2.5 trace elements of anthropogenic origin (La, V, and S) were recovered from the lung tissues of CAPs-exposed rats. Recovery of these specific trace elements was greatest in rats with OVA-induced allergic airway disease. Additional laboratory experiments using intratracheal instillations of ambient PM2.5 samples were performed to identify bioactive agents in the CAPs to which rats had been exposed in the inhalation exposure component. Because the most pronounced effects of CAPs inhalation were found in BN rats with OVA-induced allergic airways exposed in September, we used ambient PM2.5 samples that were collected on 2 days during the September CAPs inhalation exposures to use for instillation. Ambient PM2.5 samples were collected, fractionated into soluble and insoluble species, and then compared with each other and with total PM2.5 for their effects in healthy BN rats and those with OVA-induced allergic airway disease. Intratracheal instillation of the insoluble fraction of PM2.5 caused mild neutrophilic inflammation in the lungs of healthy rats. However, total PM2.5 or the soluble or insoluble fractions instilled in rats with OVA-induced airway inflammation did not enhance the inflammation or the airway epithelial remodeling that was evident in some of the BN rats exposed to CAPs by inhalation. Therefore, the results from this instillation component did not suggest what fractions of the CAPs may have been responsible for enhancing OVA-induced airway mucosubstances and pulmonary inflammation observed in the inhalation exposure component. In summary, inhaled CAPs-related pulmonary alterations in the affected OVA-challenged rats appeared to be related to the chemical composition, rather than the mass

  1. Effect of mesenchymal stem cells on inhibiting airway remodeling and airway inflammation in chronic asthma.

    PubMed

    Ge, Xiahui; Bai, Chong; Yang, Jianming; Lou, Guoliang; Li, Qiang; Chen, Ruohua

    2013-07-01

    Previous studies proved that bone marrow-derived mesenchymal stem cells (BMSCs) could improve a variety of immune-mediated disease by its immunomodulatory properties. In this study, we investigated the effect on airway remodeling and airway inflammation by administrating BMSCs in chronic asthmatic mice. Forty-eight female BALB/c mice were randomly distributed into PBS group, BMSCs treatment group, BMSCs control group, and asthmatic group. The levels of cytokine and immunoglobulin in serum and bronchoalveolar lavage fluid were detected by enzyme-linked immunosorbent assay. The number of CD4(+) CD25(+) regulatory T cells and morphometric analysis was determined by flow cytometry, hematoxylin-eosin, immunofluorescence staining, periodic-acid Schiff, and masson staining, respectively. We found that airway remodeling and airway inflammation were evident in asthmatic mice. Moreover, low level of IL-12 and high levels of IL-13, IL-4, OVA-specific IgG1, IgE, and IgG2a and the fewer number of CD4(+) CD25(+) regulatory T cells were present in asthmatic group. However, transplantation of BMSCs significantly decreased airway inflammation and airway remodeling and level of IL-4, OVA-specific IgE, and OVA-specific IgG1, but elevated level of IL-12 and the number of CD4 + CD25 + regulatory T cells in asthma (P < 0.05). However, BMSCs did not contribute to lung regeneration and had no significant effect on levels of IL-10, IFN-Y, and IL-13. In our study, BMSCs engraftment prohibited airway inflammation and airway remodeling in chronic asthmatic group. The beneficial effect of BMSCs might involved the modulation imbalance cytokine toward a new balance Th1-Th2 profiles and up-regulation of protective CD4 + CD25 + regulatory T cells in asthma, but not contribution to lung regeneration. PMID:23334934

  2. Fungal glycan interactions with epithelial cells in allergic airway disease

    PubMed Central

    Roy, René M.; Klein, Bruce S.

    2014-01-01

    Human exposure to fungi results in a wide range of health outcomes, from invasive disease or allergy to immune tolerance. Inhaled fungi contact airway epithelial cells as an early event, and this host:fungal interaction can shape the eventual immunological outcome. Emerging evidence points to exposure to fungal cell wall carbohydrates in the development of allergic airway disease. Herein, we describe determinants of fungal allergenicity, and review the responses of airway epithelial cells to fungal carbohydrates. A greater understanding of the recognition of and response to fungal carbohydrates by airway epithelial cells may lead to the development of targeted therapies that ameliorate allergic airway disease. PMID:23602359

  3. Effect of acute airway inflammation on the pulmonary antioxidant status.

    PubMed

    Deaton, Christopher M; Marlin, David J; Smith, Nicola C; Harris, Patricia A; Dagleish, Mark P; Schroter, Robert C; Kelly, Frank J

    2005-09-01

    Effects of acute airway inflammation induced by organic dust inhalation on pulmonary antioxidant status were investigated in healthy horses and horses affected by recurrent airway obstruction. Exposure to organic dust induced acute airway neutrophilia, which was associated with increases in elastase and decreases in ascorbic acid concentrations in bronchoalveolar lavage fluid. However, markers of oxidative stress were unaffected, as was hydrogen peroxide in breath condensate. Decreases in ascorbic acid correlated with increased respiratory resistance (P = .001) when both groups were combined. In conclusion, acute neutrophilic airway inflammation does not result in significant evidence of oxidative stress in horses affected by recurrent airway obstruction. PMID:16203621

  4. Oxygenation via a Biventricular Assist Device for Emergency Airway Management.

    PubMed

    Howitt, Samuel Henry; Stirling, Sarah; Krysiak, Piotr; Pate, Bryce; Maybauer, Marc Oliver

    2016-05-01

    A 56-year-old man receiving mechanical circulatory support via a biventricular assist device suffered an airway emergency secondary to bleeding into the airway. An improvised solution to gain control of the airway in the short term was devised, and an oxygenator was inserted into the circuit, providing an alternative means of gas exchange while definitive control of the airway was achieved. This case changed practice in our institution, where we now make contingency plans for emergency oxygenator insertion into the circuits of all patients with a biventricular assist device who show any sign of airway hemorrhage. PMID:27136082

  5. Cell Jamming in the Airway Epithelium.

    PubMed

    Park, Jin-Ah; Fredberg, Jeffrey J

    2016-03-01

    Hallmarks of asthma include chronic airway inflammation, progressive airway remodeling, and airway hyperresponsiveness. The initiation and perpetuation of these processes are attributable at least in part to critical events within the airway epithelium, but the underlying mechanisms remain poorly understood. New evidence now suggests that epithelial cells derived from donors without asthma versus donors with asthma, even in the absence of inflammatory cells or mediators, express modes of collective migration that innately differ not only in the amount of migration but also in the kind of migration. The maturing cell layer tends to undergo a transition from a hypermobile, fluid-like, unjammed phase in which cells readily rearrange, exchange places, and flow, to a quiescent, solid-like, jammed phase in which cells become virtually frozen in place. Moreover, the unjammed phase defines a phenotype that can be perpetuated by the compressive stresses caused by bronchospasm. Importantly, in cells derived from donors with asthma versus donors without asthma, this jamming transition becomes substantially delayed, thus suggesting an immature or dysmature epithelial phenotype in asthma. PMID:27027955

  6. Nasal Airway Resistance: Its Measurement and Regulation.

    ERIC Educational Resources Information Center

    Hamilton, Lyle H.

    1979-01-01

    Reviews studies of regulation of nasal airway resistance (Rn). Describes methods of calculating Rn by measuring pressure-flow relationship. Data are presented on improved methods for measuring Rn and effects for expiratory and inspiratory Rn after topical application of phenylephrine nasal decongestant spray. (Author/SA)

  7. 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.

  8. 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

  9. Quantitative analysis of airway abnormalities in CT

    NASA Astrophysics Data System (ADS)

    Petersen, Jens; Lo, Pechin; Nielsen, Mads; Edula, Goutham; Ashraf, Haseem; Dirksen, Asger; de Bruijne, Marleen

    2010-03-01

    A coupled surface graph cut algorithm for airway wall segmentation from Computed Tomography (CT) images is presented. Using cost functions that highlight both inner and outer wall borders, the method combines the search for both borders into one graph cut. The proposed method is evaluated on 173 manually segmented images extracted from 15 different subjects and shown to give accurate results, with 37% less errors than the Full Width at Half Maximum (FWHM) algorithm and 62% less than a similar graph cut method without coupled surfaces. Common measures of airway wall thickness such as the Interior Area (IA) and Wall Area percentage (WA%) was measured by the proposed method on a total of 723 CT scans from a lung cancer screening study. These measures were significantly different for participants with Chronic Obstructive Pulmonary Disease (COPD) compared to asymptomatic participants. Furthermore, reproducibility was good as confirmed by repeat scans and the measures correlated well with the outcomes of pulmonary function tests, demonstrating the use of the algorithm as a COPD diagnostic tool. Additionally, a new measure of airway wall thickness is proposed, Normalized Wall Intensity Sum (NWIS). NWIS is shown to correlate better with lung function test values and to be more reproducible than previous measures IA, WA% and airway wall thickness at a lumen perimeter of 10 mm (PI10).

  10. 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.

  11. Canine brachycephalic airway syndrome: surgical management.

    PubMed

    Trappler, Michelle; Moore, Kenneth

    2011-05-01

    Many surgical options have been described to treat various aspects of canine brachycephalic airway syndrome (BAS). This article describes the surgical management, postoperative care, and prognosis of this condition. The pathophysiology and medical therapy of BAS are described in a companion article. PMID:21870354

  12. 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

  13. COLCHICINE DECREASES AIRWAY HYPERACTIVITY AFTER PHOSGENE EXPOSURE

    EPA Science Inventory

    Phosgene (COCl(2)) exposure affects an influx of inflammatory cells into the lung, which can be reduced in an animal model by pretreatment with colchicine. Inflammation in the respiratory tract can be associated with an increase in airway hyperreactivity. We tested the hypotheses...

  14. REGIONAL DIFFERENCES IN AIRWAY SURFACE LIQUID COMPOSITION

    EPA Science Inventory

    Liquid from canine airway surfaces was absorbed onto filter paper strips and analyzed. In resting conditions, tracheal surface liquid was hyperosmolal (330 mosmol/kg H2O) compared to plasma with raised Na(+1) (158 meq/l), Cl(-1) (134 meq/l), K(-1) (28 meq/l), and HCO3(-1) (32 meq...

  15. Steroids for intubated croup masking airway haemangioma.

    PubMed Central

    Kiff, K M; Mok, Q; Dunne, J; Tasker, R C

    1996-01-01

    Recently, the beneficial role of steroids for acute laryngotracheobronchitis has been more clearly defined for both intubated and unintubated patients. However, corticosteroids also improve the clinical signs of airway haemangiomata. Two patients are described who illustrate how this can be a source of diagnostic confusion. PMID:8660054

  16. Airway smooth muscle responsiveness from dogs with airway hyperresponsiveness after O/sub 3/ inhalation

    SciTech Connect

    Jones, G.L.; O'Byrne, P.M.; Pashley, M.; Serio, R.; Jury, J.; Lane, C.G.; Daniel, E.E.

    1988-07-01

    Airway hyperresponsiveness occurs after inhalation of O3 in dogs. The purpose of this study was to examine the responsiveness of trachealis smooth muscle in vitro to electrical field stimulation, exogenous acetylcholine, and potassium chloride from dogs with airway hyperresponsiveness after inhaled O3 in vivo and to compare this with the responsiveness of trachealis muscle from control dogs. In addition, excitatory junction potentials were measured with the use of single and double sucrose gap techniques in both groups of dogs to determine whether inhaled O3 affects the release of acetylcholine from parasympathetic nerves in trachealis muscle. Airway hyperresponsiveness developed in all dogs after inhaled O3 (3 ppm for 30 min). The acetylcholine provocative concentration decreased from 4.11 mg/ml before O3 inhalation to 0.66 mg/ml after O3 (P less than 0.0001). The acetylcholine provocative concentration increased slightly after control inhalation of dry room air. Airway smooth muscle showed increased responses to both electrical field stimulation and exogenous acetylcholine but not to potassium chloride in preparations from dogs with airway hyperresponsiveness in vivo. The increased response to electrical field stimulation was not associated with a change in excitatory junctional potentials. These results suggest that a postjunctional alteration in trachealis muscle function occurs after inhaled O3 in dogs, which may account for airway hyperresponsiveness after O3 in vivo.

  17. BrdU Pulse Labelling In Vivo to Characterise Cell Proliferation during Regeneration and Repair following Injury to the Airway Wall in Sheep

    PubMed Central

    Yahaya, B.; McLachlan, G.; Collie, D. D. S.

    2013-01-01

    The response of S-phase cells labelled with bromodeoxyuridine (BrdU) in sheep airways undergoing repair in response to endobronchial brush biopsy was investigated in this study. Separate sites within the airway tree of anaesthetised sheep were biopsied at intervals prior to pulse labelling with BrdU, which was administered one hour prior to euthanasia. Both brushed and spatially disparate unbrushed (control) sites were carefully mapped, dissected, and processed to facilitate histological analysis of BrdU labelling. Our study indicated that the number and location of BrdU-labelled cells varied according to the age of the repairing injury. There was little evidence of cell proliferation in either control airway tissues or airway tissues examined six hours after injury. However, by days 1 and 3, BrdU-labelled cells were increased in number in the airway wall, both at the damaged site and in the regions flanking either side of the injury. Thereafter, cell proliferative activity largely declined by day 7 after injury, when consistent evidence of remodelling in the airway wall could be appreciated. This study successfully demonstrated the effectiveness of in vivo pulse labelling in tracking cell proliferation during repair which has a potential value in exploring the therapeutic utility of stem cell approaches in relevant lung disease models. PMID:23533365

  18. BrdU pulse labelling in vivo to characterise cell proliferation during regeneration and repair following injury to the airway wall in sheep.

    PubMed

    Yahaya, B; McLachlan, G; Collie, D D S

    2013-01-01

    The response of S-phase cells labelled with bromodeoxyuridine (BrdU) in sheep airways undergoing repair in response to endobronchial brush biopsy was investigated in this study. Separate sites within the airway tree of anaesthetised sheep were biopsied at intervals prior to pulse labelling with BrdU, which was administered one hour prior to euthanasia. Both brushed and spatially disparate unbrushed (control) sites were carefully mapped, dissected, and processed to facilitate histological analysis of BrdU labelling. Our study indicated that the number and location of BrdU-labelled cells varied according to the age of the repairing injury. There was little evidence of cell proliferation in either control airway tissues or airway tissues examined six hours after injury. However, by days 1 and 3, BrdU-labelled cells were increased in number in the airway wall, both at the damaged site and in the regions flanking either side of the injury. Thereafter, cell proliferative activity largely declined by day 7 after injury, when consistent evidence of remodelling in the airway wall could be appreciated. This study successfully demonstrated the effectiveness of in vivo pulse labelling in tracking cell proliferation during repair which has a potential value in exploring the therapeutic utility of stem cell approaches in relevant lung disease models. PMID:23533365

  19. 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.

  20. BLUNTING AIRWAYS EOSINOPHILIC INFLAMMATION RESULTS IN A DECREASED AIRWAY NEUTROPHIL RESPONSE TO INHALED LPS IN ATOPIC ASTHMATICS A ROLE FOR CD-14

    EPA Science Inventory

    Recent data demonstrate that atopic inflammation might enhance airway responses to inhaled LPS in individuals with atopic asthma by increasing CD14 expression on airway macrophages. We sought to determine whether blunting airway eosinophilic inflammation decreases CD14 expressio...

  1. [Airway Management in a Patient with Forestier's Disease].

    PubMed

    Kondo, Yuriko; Echigo, Noriyuki; Akata, Mariko; Yokoyama, Kaori; Takasugi, Naoya; Goto, Takahisa

    2016-04-01

    Airway management in a patient with Forestier's disease can be challenging clinically because this disease may cause not only dysphagia but also airway obstruction due to the compression of the pharynx and esophagus caused by the ossification of anterior longitudinal ligament. We report our anesthetic management in a patient with Forestier's disease. Meanwhile, we studied the causes of difficult airway and the most suitable airway device for a patient with this disease from a standpoint of anatomy of upper airway. Our study indicated the possibility that the most suitable airway device differed depending on the actual location of the ossification of anterior longitudinal ligament in the cervical spine and that more prudent airway management would be required if its lesion location extended to upper cervical spine. PMID:27188118

  2. Simulation-based airway management training: application and looking forward.

    PubMed

    Yang, Dong; Wei, Yu-Kui; Xue, Fu-Shan; Deng, Xiao-Ming; Zhi, Juan

    2016-04-01

    Within the airway management field, simulation has been used as a tool of training for over 40 years. Simulation training offers a chance of active involvement for the trainees. It can effectively enhance and upgrade the knowledge and skills of the trainees in airway management, and subsequently decrease medical errors and improve patients' outcomes and safety through a variety of airway management training modalities, such as common airway skills, difficult airway management strategies, and crisis management skills. To perform simulation-based airway management training effectively, not only are task trainers and high-fidelity simulators required but also instructors with rich experience in airway management simulation training and optimal curriculum design are essential. PMID:26671260

  3. 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

  4. 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

  5. Kaempferol Inhibits Endoplasmic Reticulum Stress-Associated Mucus Hypersecretion in Airway Epithelial Cells And Ovalbumin-Sensitized Mice

    PubMed Central

    Choi, Yean-Jung; Kang, Min-Kyung; Kim, Yun-Ho; Kang, Young-Hee

    2015-01-01

    Mucus hypersecretion is an important pathological feature of chronic airway diseases, such as asthma and pulmonary diseases. MUC5AC is a major component of the mucus matrix forming family of mucins in the airways. The initiation of endoplasmic reticulum (ER)-mediated stress responses contributes to the pathogenesis of airway diseases. The present study investigated that ER stress was responsible for airway mucus production and this effect was blocked by the flavonoid kaempferol. Oral administration of ≥10 mg/kg kaempferol suppressed mucus secretion and goblet cell hyperplasia observed in the bronchial airway and lung of BALB/c mice sensitized with ovalbumin (OVA). TGF-β and tunicamycin promoted MUC5AC induction after 72 h in human bronchial airway epithelial BEAS-2B cells, which was dampened by 20 μM kaempferol. Kaempferol inhibited tunicamycin-induced ER stress of airway epithelial cells through disturbing the activation of the ER transmembrane sensor ATF6 and IRE1α. Additionally, this compound demoted the induction of ER chaperones such as GRP78 and HSP70 and the splicing of XBP-1 mRNA by tunicamycin. The in vivo study further revealed that kaempferol attenuated the induction of XBP-1 and IRE1α in epithelial tissues of OVA-challenged mice. TGF-β and tunicamycin induced TRAF2 with JNK activation and such induction was deterred by kaempferol. The inhibition of JNK activation encumbered the XBP-1 mRNA splicing and MUC5AC induction by tunicamycin and TGF-β. These results demonstrate that kaempferol alleviated asthmatic mucus hypersecretion through blocking bronchial epithelial ER stress via the inhibition of IRE1α-TRAF2-JNK activation. Therefore, kaempferol may be a potential therapeutic agent targeting mucus hypersecretion-associated pulmonary diseases. PMID:26599511

  6. 12/15-Lipoxygenase deficiency protects mice from allergic airways inflammation and increases secretory IgA levels

    PubMed Central

    Hajek, Amanda R.; Lindley, Alexa R.; Favoreto, Silvio; Carter, Roderick; Schleimer, Robert P.; Kuperman, Douglas A.

    2009-01-01

    Background Induction of 15-lipoxygenase-1 (15-LO-1) has been observed in the airways of subjects with asthma, although its physiologic role in the airways has remained largely undefined. Objectives We sought to test the hypothesis that the mouse 15-LO-1 ortholog 12/15-LO contributes to the development of allergic airways inflammation. Methods Two models were used to evaluate wild-type and 12/15-LO–deficient mice. The systemic model involved intraperitoneal injections of allergen, and the mucosal model involved allergen exposures occurring exclusively in the airways. The systemic and mucosal-specific contributions of 12/15-LO to allergic sensitization and airways inflammation were determined by comparing the results obtained in the 2 models. Results In the mucosal model 12/15-LO knockout mice were protected from the development of allergic sensitization and airways inflammation, as evidenced by circulating levels of allergen-specific IgE, IgG1, and IgG2a; the profile of inflammatory cells in bronchoalveolar lavage fluid; and the expression of cytokines and mediators in lung tissue. In the systemic model 12/15-LO knockout mice were not protected. This suggested the presence of a lung-restricted protective role for 12/15-LO deficiency that was potentially accounted for by increased activation of mucosal B cells and increased production of the known mucosal-specific protective mediator secretory IgA. Conclusions Induction of 15-LO-1 in asthma might contribute to allergic sensitization and airways inflammation, potentially by causing suppression of secretory IgA. PMID:18692885

  7. Pharmacological modulation of inhaled sodium metabisulphite-induced airway microvascular leakage and bronchoconstriction in the guinea-pig.

    PubMed Central

    Sakamoto, T.; Elwood, W.; Barnes, P. J.; Chung, K. F.

    1992-01-01

    1. We have investigated the effects of chlorpheniramine, atropine and capsaicin pretreatment on inhaled sodium metabisulphite (MBS)-induced airway microvascular leakage and bronchoconstriction in anaesthetized guinea-pigs in order to clarify the mechanisms involved in these responses. The effects of frusemide and nedocromil sodium were also examined. 2. Lung resistance (RL) was measured for 6 min after inhalation of MBS (20, 40, 80 and 200 mM; 30 breaths), followed by measurement of extravasation of Evans blue dye into airway tissues, used as an index of airway microvascular leakage. MBS caused an increase in RL and leakage of dye at all airway levels in a dose-dependent manner. 3. Chlorpheniramine (10 mg kg-1, i.v.), atropine (1 mg kg-1, i.v.), their combination or inhaled nedocromil sodium (10 mg ml-1, 7 min) had no effect against the airway microvascular leakage induced by 80 mM MBS (30 breaths). Capsaicin pretreatment (50 mg kg-1, s.c.) caused a significant decrease in the leakage of dye in the main bronchi and inhaled frusemide (10 mg ml-1, 7 min) also in the main bronchi and proximal intrapulmonary airway. 4. Chlorpheniramine, atropine, their combination, capsaicin pretreatment and frusemide, but not nedocromil sodium, inhibited significantly the peak RL induced by 80 mM MBS (30 breaths) by approximately 50%. 5. We conclude that a cholinergic reflex and neuropeptides released from sensory nerve endings may participate in the mechanisms of MBS-induced airway responses. Frusemide but not nedocromil sodium may have an inhibitor effect on these neural mechanisms. The inhibitory effect of nedocromil sodium against lower doses of MBS is not excluded. PMID:1330180

  8. Airway Hydration, Apical K(+) Secretion, and the Large-Conductance, Ca(2+)-activated and Voltage-dependent Potassium (BK) Channel.

    PubMed

    Kis, Adrian; Krick, Stefanie; Baumlin, Nathalie; Salathe, Matthias

    2016-04-01

    Large-conductance, calcium-activated, and voltage-gated K(+) (BK) channels are expressed in many tissues of the human body, where they play important roles in signaling not only in excitable but also in nonexcitable cells. Because BK channel properties are rendered in part by their association with four β and four γ subunits, their channel function can differ drastically, depending on in which cellular system they are expressed. Recent studies verify the importance of apically expressed BK channels for airway surface liquid homeostasis and therefore of their significant role in mucociliary clearance. Here, we review evidence that inflammatory cytokines, which contribute to airway diseases, can lead to reduced BK activity via a functional down-regulation of the γ regulatory subunit LRRC26. Therefore, manipulation of LRRC26 and pharmacological opening of BK channels represent two novel concepts of targeting epithelial dysfunction in inflammatory airway diseases. PMID:27115952

  9. Airway oxidative stress in chronic cough

    PubMed Central

    2013-01-01

    Background The mechanisms of chronic cough are unclear. Many reactive oxygen species affect airway sensory C-fibres which are capable to induce cough. Several chronic lung diseases are characterised by cough and oxidative stress. In asthma, an association between the cough severity and airway oxidative stress has been demonstrated. The present study was conducted to investigate whether airway oxidative stress is associated with chronic cough in subjects without chronic lung diseases. Methods Exhaled breath condensate samples were obtained in 43 non-smoking patients with chronic cough and 15 healthy subjects. Exclusion criteria included a doctor’s diagnosis of any lung disorders and any abnormality in lung x-ray. The concentration of 8-isoprostane was measured. In addition, the patients filled in Leicester Cough Questionnaire and underwent hypertonic saline cough provocation test, spirometry, ambulatory peak flow monitoring, nitric oxide measurement, and histamine airway challenge. In a subgroup of patients the measurements were repeated during 12 weeks’ treatment with inhaled budesonide, 800 ug/day. Results The 8-isoprostane concentrations were higher in the cough patients than in the healthy subjects (24.6 ± 1.2 pg/ml vs. 10.1 ± 1.7 pg/ml, p = 0.045). The 8-isoprostane concentration was associated with the Leicester Cough Questionnaire total score (p = 0.044) but not with the cough sensitivity to saline or other tests. Budesonide treatment did not affect the 8-isoprostane concentrations. Conclusions Chronic cough seems to be associated with airway oxidative stress in subjects with chronic cough but without chronic lung diseases. This finding may help to develop novel antitussive drugs. Trial registration The study was registered in ClinicalTrials.gov database (KUH5801112), identifier NCT00859274. PMID:24294924

  10. Innate Immune Responses to Engineered Nanomaterials During Allergic Airway Inflammation

    NASA Astrophysics Data System (ADS)

    Shipkowski, Kelly Anne

    disease would modulate the innate immune response to MWCNTs. We hypothesized that Th2 cytokines and the allergic asthmatic microenvironment would alter MWCNT-induced inflammasome activation and IL- 1beta secretion both in vitro and in vivo. In vitro, THP-1 cells, a human monocytic cell line, were differentiated into macrophages and exposed to MWCNTs and or recombinant Th2 cytokines, specifically IL-4 and/or IL-13. Exposure of THP-1 cells to MWCNTs alone caused dose-dependent secretion of IL-1beta, while co-exposure to IL-4 and/or IL-13 suppressed MWCNT-induced IL-1beta. Further analysis determined that IL-4 and IL-13 were phosphorylating the protein signal transducer and activator of transcription 6 (STAT6) and subsequently inhibiting inflammasome activation and function through suppression of caspase-1, a cysteine protease responsible for cleavage of pro-IL-1beta into an active, secretable form. In vivo, wild-type C57BL6 mice were sensitized intranasally with HDM allergen and exposed to MWCNTs via oropharyngeal aspiration. Treatment with MWCNTs alone induced secretion of IL-1beta in the bronchoalveolar lavage fluid (BALF) one day post-exposure, while sensitization with HDM prior to MWCNT exposure suppressed MWCNT-induced IL-1beta. Immunohistochemical (IHC) analysis of lung sections from exposed animals showed that HDM sensitization inhibited MWCNT-induced pro-casapse-1 protein expression, responsible for inflammasome activation, in the airway epithelium and macrophages. MWCNT exposure combined with HDM sensitization increased inflammatory cell infiltration and subsequent acute lung inflammation and chronic fibrosis. Analysis of the systemic effects of MWCNT exposure during allergic airway sensitization showed that MWCNTs and/or HDM allergen upregulated STAT3 mRNA expression in the lungs, liver, and spleen of exposed animals, and at the same induced mixed T helper (Th) responses in the different tissues. Collectively, these data suggest that the allergic microenvironment

  11. Brief mechanical ventilation causes differential epithelial repair along the airways of fetal, preterm lambs.

    PubMed

    Deptula, Nicole; Royse, Emily; Kemp, Matthew W; Miura, Yuichiro; Kallapur, Suhas G; Jobe, Alan H; Hillman, Noah H

    2016-08-01

    Mechanical ventilation of preterm lambs causes lung inflammation and injury to the airway epithelium, which is repaired by 15 days after ventilation. In mice, activated basal cells (p63+, KRT14+, KRT8+) initiate injury repair to the trachea, whereas club cells coordinate distal airway repair. In both human and sheep, basal cells line the pseudostratified airways to the distal bronchioles with club cells only present in terminal bronchioles. Mechanical ventilation causes airway epithelial injury that is repaired through basal cell activation in the fetal lung. Ewes at 123 ± 1 day gestational age had the head and chest of the fetus exteriorized and tracheostomy placed. With placental circulation intact, fetal lambs were mechanically ventilated with up to 15 ml/kg for 15 min with 95% N2/5% CO2 Fetal lambs were returned to the uterus for up to 24 h. The trachea, left mainstem bronchi, and peripheral lung were evaluated for epithelial injury and cellular response consistent with repair. Peripheral lung tissue had inflammation, pro-inflammatory cytokine production, epithelial growth factor receptor ligand upregulation, increased p63 expression, and proliferation of pro-SPB, TTF-1 positive club cells. In bronchi, KRT14 and KRT8 mRNA increased without increases in Notch pathway mRNA or proliferation. In trachea, mRNA increased for Notch ligands, SAM pointed domain-containing Ets transcription factor and mucin 5B, but not for basal cell markers. A brief period of mechanical ventilation causes differential epithelial activation between trachea, bronchi, and peripheral lung. The repair mechanisms identified in adult mice occur at different levels of airway branching in fetal sheep with basal and club cell activation. PMID:27343193

  12. CARMA3 Is Critical for the Initiation of Allergic Airway Inflammation.

    PubMed

    Causton, Benjamin; Ramadas, Ravisankar A; Cho, Josalyn L; Jones, Khristianna; Pardo-Saganta, Ana; Rajagopal, Jayaraj; Xavier, Ramnik J; Medoff, Benjamin D

    2015-07-15

    Innate immune responses to allergens by airway epithelial cells (AECs) help initiate and propagate the adaptive immune response associated with allergic airway inflammation in asthma. Activation of the transcription factor NF-κB in AECs by allergens or secondary mediators via G protein-coupled receptors (GPCRs) is an important component of this multifaceted inflammatory cascade. Members of the caspase recruitment domain family of proteins display tissue-specific expression and help mediate NF-κB activity in response to numerous stimuli. We have previously shown that caspase recruitment domain-containing membrane-associated guanylate kinase protein (CARMA)3 is specifically expressed in AECs and mediates NF-κB activation in these cells in response to stimulation with the GPCR agonist lysophosphatidic acid. In this study, we demonstrate that reduced levels of CARMA3 in normal human bronchial epithelial cells decreases the production of proasthmatic mediators in response to a panel of asthma-relevant GPCR ligands such as lysophosphatidic acid, adenosine triphosphate, and allergens that activate GPCRs such as Alternaria alternata and house dust mite. We then show that genetically modified mice with CARMA3-deficient AECs have reduced airway eosinophilia and proinflammatory cytokine production in a murine model of allergic airway inflammation. Additionally, we demonstrate that these mice have impaired dendritic cell maturation in the lung and that dendritic cells from mice with CARMA3-deficient AECs have impaired Ag processing. In conclusion, we show that AEC CARMA3 helps mediate allergic airway inflammation, and that CARMA3 is a critical signaling molecule bridging the innate and adaptive immune responses in the lung. PMID:26041536

  13. CARMA3 Is Critical for the Initiation of Allergic Airway Inflammation

    PubMed Central

    Causton, Benjamin; Ramadas, Ravisankar A.; Cho, Josalyn L.; Jones, Khristianna; Pardo-Saganta, Ana; Rajagopal, Jayaraj; Xavier, Ramnik J.

    2015-01-01

    Innate immune responses to allergens by airway epithelial cells (AECs) help initiate and propagate the adaptive immune response associated with allergic airway inflammation in asthma. Activation of the transcription factor NF-κB in AECs by allergens or secondary mediators via G protein–coupled receptors (GPCRs) is an important component of this multifaceted inflammatory cascade. Members of the caspase recruitment domain family of proteins display tissue-specific expression and help mediate NF-κB activity in response to numerous stimuli. We have previously shown that caspase recruitment domain–containing membrane-associated guanylate kinase protein (CARMA)3 is specifically expressed in AECs and mediates NF-κB activation in these cells in response to stimulation with the GPCR agonist lysophosphatidic acid. In this study, we demonstrate that reduced levels of CARMA3 in normal human bronchial epithelial cells decreases the production of proasthmatic mediators in response to a panel of asthma-relevant GPCR ligands such as lysophosphatidic acid, adenosine triphosphate, and allergens that activate GPCRs such as Alternaria alternata and house dust mite. We then show that genetically modified mice with CARMA3-deficient AECs have reduced airway eosinophilia and proinflammatory cytokine production in a murine model of allergic airway inflammation. Additionally, we demonstrate that these mice have impaired dendritic cell maturation in the lung and that dendritic cells from mice with CARMA3-deficient AECs have impaired Ag processing. In conclusion, we show that AEC CARMA3 helps mediate allergic airway inflammation, and that CARMA3 is a critical signaling molecule bridging the innate and adaptive immune responses in the lung. PMID:26041536

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

    PubMed

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

    2015-11-01

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

  15. Regulation of airway contractility by plasminogen activators through N-methyl-D-aspartate receptor-1.

    PubMed

    Nassar, Taher; Yarovoi, Serge; Fanne, Rami Abu; Akkawi, Sa'ed; Jammal, Mahmud; Allen, Timothy Craig; Idell, Steven; Cines, Douglas B; Higazi, Abd Al-Roof

    2010-12-01

    Reactive airway disease is mediated by smooth muscle contraction initiated through several agonist-dependent pathways. Activation of type 1 N-methyl-D-aspartate receptors (NMDA-R1s) by plasminogen activators (PAs) has been linked to control of vascular tone, but their effect on airway smooth muscle contractility has not previously been studied to our knowledge. We observed that NMDA-R1s are expressed by human airway smooth muscle cells and constitutively inhibit the contraction of isolated rat tracheal rings in response to acetylcholine (Ach). Both tissue-type PA (tPA) and urokinase-type PA (uPA) bind to NMDA-R1 and reverse this effect, thereby enhancing Ach-induced tracheal contractility. Tracheal contractility initiated by Ach is reduced in rings isolated from tPA(-/-) and uPA(-/-) mice compared with their wild-type counterparts. The procontractile effect of uPA or tPA was mimicked and augmented by the nitric oxide synthase inhibitor, l-NAME. uPA and tPA further enhanced the contractility of rings denuded of epithelium, an effect that was inhibited by the NMDA-R antagonist, MK-801. Binding of PAs to NMDA-R1 and the subsequent activation of the receptor were inhibited by PA inhibitor type 1, by a PA inhibitor type 1-derived hexapeptide that recognizes the tPA and uPA docking domains, as well as by specific mutations within the docking site of tPA. These studies identify involvement of PAs and NMDA-R1 in airway contractility, and define new loci that could lead to the development of novel interventions for reactive airway disease. PMID:20097831

  16. Detection of Upper Airway Status and Respiratory Events by a Current Generation Positive Airway Pressure Device

    PubMed Central

    Li, Qing Yun; Berry, Richard B.; Goetting, Mark G.; Staley, Bethany; Soto-Calderon, Haideliza; Tsai, Sheila C.; Jasko, Jeffrey G.; Pack, Allan I.; Kuna, Samuel T.

    2015-01-01

    Study Objectives: To compare a positive airway pressure (PAP) device's detection of respiratory events and airway status during device-detected apneas with events scored on simultaneous polysomnography (PSG). Design: Prospective PSGs of patients with sleep apnea using a new-generation PAP device. Settings: Four clinical and academic sleep centers. Patients: Forty-five patients with obstructive sleep apnea (OSA) and complex sleep apnea (Comp SA) performed a PSG on PAP levels adjusted to induce respiratory events. Interventions: None. Measurements and Results: PAP device data identifying the type of respiratory event and whether the airway during a device-detected apnea was open or obstructed were compared to time-synced, manually scored respiratory events on simultaneous PSG recording. Intraclass correlation coefficients between device-detected and PSG scored events were 0.854 for apnea-hypopnea index (AHI), 0.783 for apnea index, 0.252 for hypopnea index, and 0.098 for respiratory event-related arousals index. At a device AHI (AHIFlow) of 10 events/h, area under the receiver operating characteristic curve was 0.98, with sensitivity 0.92 and specificity 0.84. AHIFlow tended to overestimate AHI on PSG at values less than 10 events/h. The device detected that the airway was obstructed in 87.4% of manually scored obstructive apneas. Of the device-detected apneas with clear airway, a minority (15.8%) were manually scored as obstructive apneas. Conclusions: A device-detected apnea-hypopnea index (AHIFlow) < 10 events/h on a positive airway pressure device is strong evidence of good treatment efficacy. Device-detected airway status agrees closely with the presumed airway status during polysomnography scored events, but should not be equated with a specific type of respiratory event. Citation: Li QY, Berry RB, Goetting MG, Staley B, Soto-Calderon H, Tsai SC, Jasko JG, Pack AI, Kuna ST. Detection of upper airway status and respiratory events by a current generation positive

  17. Syntaxin 1A is expressed in airway epithelial cells, where it modulates CFTR Cl– currents

    PubMed Central

    Naren, Anjaparavanda P.; Di, Anke; Cormet-Boyaka, Estelle; Boyaka, Prosper N.; McGhee, Jerry R.; Zhou, Weihong; Akagawa, Kimio; Fujiwara, Tomonori; Thome, Ulrich; Engelhardt, John F.; Nelson, Deborah J.; Kirk, Kevin L.

    2000-01-01

    The CFTR Cl– channel controls salt and water transport across epithelial tissues. Previously, we showed that CFTR-mediated Cl– currents in the Xenopus oocyte expression system are inhibited by syntaxin 1A, a component of the membrane trafficking machinery. This negative modulation of CFTR function can be reversed by soluble syntaxin 1A peptides and by the syntaxin 1A binding protein, Munc-18. In the present study, we determined whether syntaxin 1A is expressed in native epithelial tissues that normally express CFTR and whether it modulates CFTR currents in these tissues. Using immunoblotting and immunofluorescence, we observed syntaxin 1A in native gut and airway epithelial tissues and showed that epithelial cells from these tissues express syntaxin 1A at >10-fold molar excess over CFTR. Syntaxin 1A is seen near the apical cell surfaces of human bronchial airway epithelium. Reagents that disrupt the CFTR-syntaxin 1A interaction, including soluble syntaxin 1A cytosolic domain and recombinant Munc-18, augmented cAMP-dependent CFTR Cl– currents by more than 2- to 4-fold in mouse tracheal epithelial cells and cells derived from human nasal polyps, but these reagents did not affect CaMK II–activated Cl– currents in these cells. PMID:10675364

  18. NK cells contribute to persistent airway inflammation and AHR during the later stage of RSV infection in mice.

    PubMed

    Long, Xiaoru; Xie, Jun; Zhao, Keting; Li, Wei; Tang, Wei; Chen, Sisi; Zang, Na; Ren, Luo; Deng, Yu; Xie, Xiaohong; Wang, Lijia; Fu, Zhou; Liu, Enmei

    2016-10-01

    RSV can lead to persistent airway inflammation and AHR and is intimately associated with childhood recurrent wheezing and asthma, but the underlying mechanisms remain unclear. There are high numbers of NK cells in the lung, which not only play important roles in the acute stage of RSV infection, but also are pivotal in regulating the pathogenesis of asthma. Therefore, in this study, we assumed that NK cells might contribute to persistent airway disease during the later stage of RSV infection. Mice were killed at serial time points after RSV infection to collect samples. Leukocytes in bronchoalveolar lavage fluid (BALF) were counted, lung histopathology was examined, and airway hyperresponsiveness (AHR) was measured by whole-body plethysmography. Cytokines were detected by ELISA, and NK cells were determined by flow cytometry. Rabbit anti-mouse asialo-GM-1 antibodies and resveratrol were used to deplete or suppress NK cells. Inflammatory cells in BALF, lung tissue damage and AHR were persistent for 60 days post-RSV infection. Type 2 cytokines and NK cells were significantly increased during the later stage of infection. When NK cells were decreased by the antibodies or resveratrol, type 2 cytokines, the persistent airway inflammation and AHR were all markedly reduced. NK cells can contribute to the RSV-associated persistent airway inflammation and AHR at least partially by promoting type 2 cytokines. Therefore, therapeutic targeting of NK cells may provide a novel approach to alleviating the recurrent wheezing subsequent to RSV infection. PMID:27329138

  19. Production of 3-D Airway Organoids From Primary Human Airway Basal Cells and Their Use in High-Throughput Screening.

    PubMed

    Hild, Marc; Jaffe, Aron B

    2016-01-01

    The ability of human airway basal cells to serve as progenitor cells in the conducting airway makes them an attractive target in a number of respiratory diseases associated with epithelial remodeling. This unit describes a protocol for the culture of 'bronchospheres', three-dimensional (3-D) organoids that are derived from primary human airway basal cells. Mature bronchospheres are composed of functional multi-ciliated cells, mucin-producing goblet cells, and airway basal cells. In contrast to existing methods used for the culture of well-differentiated human airway epithelial cells, bronchospheres do not require growth on a permeable support and can be cultured in 384-well assay plates. The system provides a mechanism for investigating the regulation of basal cell fate during airway epithelial morphogenesis, as well as a basis for studying the function of the human airway epithelium in high-throughput assays. © 2016 by John Wiley & Sons, Inc. PMID:27171795

  20. Absence of cholinergic airway tone in normal BALB/c mice.

    PubMed

    Larcombe, Alexander N; Zosky, Graeme R; Bozanich, Elizabeth M; Turner, Debra J; Hantos, Zoltan; Sly, Peter D

    2008-05-31

    Basal airway smooth muscle (ASM) tone has not been demonstrated in mice in vivo. To determine whether basal ASM tone is present in mouse airways we measured respiratory system impedance (Zrs) before and after either atropine or bilateral vagotomy. Zrs was measured using forced oscillations delivered via a wave-tube during slow ( approximately 35s) inflation-deflation maneuvers between transrespiratory pressures (Prs) of 0 and 20 cm H2O. A constant-phase tissue model was applied to the Zrs to calculate airway resistance (R aw), tissue damping (G) and elastance (H). Thoracic gas volume (TGV) was determined plethysmographically at Prs=0 cm H2O and by integration of the inspiratory flow. The relationship between conductance (G aw=1/R aw) and TGV during inflation was also examined. Neither atropine nor vagotomy produced any change in R aw, H, eta (=G/H), TGV or the slope of G aw vs. TGV that was different to that observed in the relevant control groups. These data show that BALB/c mice do not have cholinergic ASM tone in vivo. PMID:18440286

  1. IL-17A impairs host tolerance during airway chronic infection by Pseudomonas aeruginosa.

    PubMed

    Lorè, Nicola Ivan; Cigana, Cristina; Riva, Camilla; De Fino, Ida; Nonis, Alessandro; Spagnuolo, Lorenza; Sipione, Barbara; Cariani, Lisa; Girelli, Daniela; Rossi, Giacomo; Basso, Veronica; Colombo, Carla; Mondino, Anna; Bragonzi, Alessandra

    2016-01-01

    Resistance and tolerance mechanisms participate to the interplay between host and pathogens. IL-17-mediated response has been shown to be crucial for host resistance to respiratory infections, whereas its role in host tolerance during chronic airway colonization is still unclear. Here, we investigated whether IL-17-mediated response modulates mechanisms of host tolerance during airways chronic infection by P. aeruginosa. First, we found that IL-17A levels were sustained in mice at both early and advanced stages of P. aeruginosa chronic infection and confirmed these observations in human respiratory samples from cystic fibrosis patients infected by P. aeruginosa. Using IL-17a(-/-) or IL-17ra(-/-) mice, we found that the deficiency of IL-17A/IL-17RA axis was associated with: i) increased incidence of chronic infection and bacterial burden, indicating its role in the host resistance to P. aeruginosa; ii) reduced cytokine levels (KC), tissue innate immune cells and markers of tissue damage (pro-MMP-9, elastin degradation, TGF-β1), proving alteration of host tolerance. Blockade of IL-17A activity by a monoclonal antibody, started when chronic infection is established, did not alter host resistance but increased tolerance. In conclusion, this study identifies IL-17-mediated response as a negative regulator of host tolerance during P. aeruginosa chronic airway infection. PMID:27189736

  2. Crackle-sound recording to monitor airway closure and recruitment in ventilated pigs.

    PubMed

    Peták, F; Habre, W; Babik, B; Tolnai, J; Hantos, Z

    2006-04-01

    It was hypothesised that the recruitment of atelectatic lung areas is signified by changes in the airway and tissue mechanics, and by the appearance of crackle activity attributed to the sudden reopening of collapsed airways. The authors also assumed that the acoustic activity is an earlier indicator of lung recruitment than the change in the overall mechanical state of the lungs. Six thoracotomised and mechanically ventilated mini-pigs were studied. Low-frequency pulmonary impedance was measured at end-expiratory pauses at transpulmonary pressures of 4 and 1 hPa to estimate airway resistance (Raw) and the coefficient of lung tissue elastance (H), and tracheal sounds were recorded during subsequent slow inflations to 30 hPa, in the control state and following increasing doses of i.v. methacholine (Mch). Raw and H were higher at baseline and increased more in response to Mch at 1 hPa than at 4 hPa. The crackles detected during the subsequent inflations were concentrated around and associated with the development of the lower knee of the pressure-volume curve. The number of crackles increased faster following the Mch doses and reached statistical significance earlier than Raw and H. Crackle recording during mechanical ventilation can be employed as a simple method with which to monitor lung recruitment-derecruitment. PMID:16585089

  3. IL-17A impairs host tolerance during airway chronic infection by Pseudomonas aeruginosa

    PubMed Central

    Lorè, Nicola Ivan; Cigana, Cristina; Riva, Camilla; De Fino, Ida; Nonis, Alessandro; Spagnuolo, Lorenza; Sipione, Barbara; Cariani, Lisa; Girelli, Daniela; Rossi, Giacomo; Basso, Veronica; Colombo, Carla; Mondino, Anna; Bragonzi, Alessandra

    2016-01-01

    Resistance and tolerance mechanisms participate to the interplay between host and pathogens. IL-17-mediated response has been shown to be crucial for host resistance to respiratory infections, whereas its role in host tolerance during chronic airway colonization is still unclear. Here, we investigated whether IL-17-mediated response modulates mechanisms of host tolerance during airways chronic infection by P. aeruginosa. First, we found that IL-17A levels were sustained in mice at both early and advanced stages of P. aeruginosa chronic infection and confirmed these observations in human respiratory samples from cystic fibrosis patients infected by P. aeruginosa. Using IL-17a−/− or IL-17ra−/− mice, we found that the deficiency of IL-17A/IL-17RA axis was associated with: i) increased incidence of chronic infection and bacterial burden, indicating its role in the host resistance to P. aeruginosa; ii) reduced cytokine levels (KC), tissue innate immune cells and markers of tissue damage (pro-MMP-9, elastin degradation, TGF-β1), proving alteration of host tolerance. Blockade of IL-17A activity by a monoclonal antibody, started when chronic infection is established, did not alter host resistance but increased tolerance. In conclusion, this study identifies IL-17-mediated response as a negative regulator of host tolerance during P. aeruginosa chronic airway infection. PMID:27189736

  4. Cell migration leads to spatially distinct but clonally related airway cancer precursors

    PubMed Central

    Pipinikas, Christodoulos P; Kiropoulos, Theodoros S; Teixeira, Vitor H; Brown, James M; Varanou, Aikaterini; Falzon, Mary; Capitanio, Arrigo; Bottoms, Steven E; Carroll, Bernadette; Navani, Neal; McCaughan, Frank; George, Jeremy P; Giangreco, Adam; Wright, Nicholas A; McDonald, Stuart A C; Graham, Trevor A; Janes, Sam M

    2014-01-01

    Background Squamous cell carcinoma of the lung is a common cancer with 95% mortality at 5 years. These cancers arise from preinvasive lesions, which have a natural history of development progressing through increasing severity of dysplasia to carcinoma in situ (CIS), and in some cases, ending in transformation to invasive carcinoma. Synchronous preinvasive lesions identified at autopsy have been previously shown to be clonally related. Methods Using autofluorescence bronchoscopy that allows visual observation of preinvasive lesions within the upper airways, together with molecular profiling of biopsies using gene sequencing and loss-of-heterozygosity analysis from both preinvasive lesions and from intervening normal tissue, we have monitored individual lesions longitudinally and documented their visual, histological and molecular relationship. Results We demonstrate that rather than forming a contiguous field of abnormal tissue, clonal CIS lesions can develop at multiple anatomically discrete sites over time. Further, we demonstrate that patients with CIS in the trachea have invariably had previous lesions that have migrated proximally, and in one case, into the other lung over a period of 12 years. Conclusions Molecular information from these unique biopsies provides for the first time evidence that field cancerisation of the upper airways can occur through cell migration rather than via local contiguous cellular expansion as previously thought. Our findings urge a clinical strategy of ablating high-grade premalignant airway lesions with subsequent attentive surveillance for recurrence in the bronchial tree. PMID:24550057

  5. Does the length dependency of airway smooth muscle force contribute to airway hyperresponsiveness?

    PubMed

    Lee-Gosselin, Audrey; Pascoe, Chris D; Couture, Christian; Paré, Peter D; Bossé, Ynuk

    2013-11-01

    Airway wall remodeling and lung hyperinflation are two typical features of asthma that may alter the contractility of airway smooth muscle (ASM) by affecting its operating length. The aims of this study were as follows: 1) to describe in detail the "length dependency of ASM force" in response to different spasmogens; and 2) to predict, based on morphological data and a computational model, the consequence of this length dependency of ASM force on airway responsiveness in asthmatic subjects who have both remodeled airway walls and hyperinflated lungs. Ovine tracheal ASM strips and human bronchial rings were isolated and stimulated to contract in response to increasing concentrations of spasmogens at three different lengths. Ovine tracheal strips were more sensitive and generated greater force at longer lengths in response to acetylcholine (ACh) and K(+). Equipotent concentrations of ACh were approximately a log less for ASM stretched by 30% and approximately a log more for ASM shortened by 30%. Similar results were observed in human bronchi in response to methacholine. Morphometric and computational analyses predicted that the ASM of asthmatic subjects may be elongated by 6.6-10.4% (depending on airway generation) due to remodeling and/or hyperinflation, which could increase ACh-induced force by 1.8-117.8% (depending on ASM length and ACh concentration) and enhance the increased resistance to airflow by 0.4-4,432.8%. In conclusion, elongation of ASM imposed by airway wall remodeling and/or hyperinflation may allow ASM to operate at a longer length and to consequently generate more force and respond to lower concentration of spasmogens. This phenomenon could contribute to airway hyperresponsiveness. PMID:23970527

  6. The Role of the Extracellular Matrix Protein Mindin in Airway Response to Environmental Airways Injury

    PubMed Central

    Frush, Sarah; Li, Zhuowei; Potts, Erin N.; Du, Wanglei; Eu, Jerry P.; Garantziotis, Stavros; He, You-Wen; Foster, W. Michael

    2011-01-01

    Background: Our previous work demonstrated that the extracellular matrix protein mindin contributes to allergic airways disease. However, the role of mindin in nonallergic airways disease has not previously been explored. Objectives: We hypothesized that mindin would contribute to airways disease after inhalation of either lipopolysaccharide (LPS) or ozone. Methods: We exposed C57BL/6J and mindin-deficient (–/–) mice to aerosolized LPS (0.9 μg/m3 for 2.5 hr), saline, ozone (1 ppm for 3 hr), or filtered air (FA). All mice were evaluated 4 hr after LPS/saline 
exposure or 24 hr after ozone/FA exposure. We characterized the physiological and biological responses by analysis of airway hyperresponsiveness (AHR) with a computer-controlled small-animal ventilator (FlexiVent), inflammatory cellular recruitment, total protein in bronchoalveolar lavage fluid (BALF), proinflammatory cytokine profiling, and ex vivo bronchial ring studies. Results: After inhalation of LPS, mindin–/– mice demonstrated significantly reduced total cell and neutrophil recruitment into the airspace compared with their wild-type counterparts. Mindin–/– mice also exhibited reduced proinflammatory cytokine production and lower AHR to methacholine challenge by FlexiVent. After inhalation of ozone, mice had no detectible differences in cellular inflammation or total BALF protein dependent on mindin. However, mindin–/– mice were protected from increased proinflammatory cytokine production and AHR compared with their C57BL/6J counterparts. After ozone exposure, bronchial rings derived from mindin–/– mice demonstrated reduced constriction in response to carbachol. Conclusions: These data demonstrate that the extracellular matrix protein mindin modifies the airway response to both LPS and ozone. Our data support a conserved role of mindin in production of proinflammatory cytokines and the development of AHR in two divergent models of reactive airways disease, as well as a role of

  7. Microarray gene expression analysis of the human airway in patients exposed to sulfur mustard.

    PubMed

    Najafi, Ali; Masoudi-Nejad, Ali; Imani Fooladi, Abbas Ali; Ghanei, Mostafa; Nourani, Mohamad Reza

    2014-08-01

    There is much data about the acute effects of sulfur mustard gas on humans, animals and cells. But less is known regarding the molecular basics of chronic complications in humans. Basically, mustard gas, as an alkylating agent, causes several chronic problems in the eyes, skin and more importantly in the pulmonary system which is the main cause of death. Although recent proteomic research has been carried out on bronchoalveolar lavage (BAL) and serum, but high-throughput transcriptomics have not yet been applied to chronic airway remodeling. This is the first cDNA-microarray report on the chronic human mustard lung disease, 25 years after exposure during the Iran-Iraq war. Microarray transcriptional profiling indicated that a total of 122 genes were significantly dysregulated in tissues located in the airway of patients. These genes are associated with the extracellular matrix components, apoptosis, stress response, inflammation and mucus secretion. PMID:24823320

  8. Intranasal epidermoid cyst causing upper airway obstruction in three brachycephalic dogs.

    PubMed

    Murgia, D; Pivetta, M; Bowlt, K; Volmer, C; Holloway, A; Dennis, R

    2014-08-01

    This case report describes three brachycephalic dogs with intranasal epidermoid cysts that were causing additional upper airway obstruction. Although epidermoid cysts have been described in several locations in dogs, to the authors' knowledge intranasal epidermoid cysts have not been previously reported. All dogs had mucopurulent to haemorrhagic nasal discharge. Magnetic resonance imaging of the head revealed the presence of unilateral or bilateral intranasal cystic lesions obstructing the nasal cavities partially or completely, with atrophy of the ipsilateral nasal turbinates. The cystic lesions were surgically excised in all dogs using a modified lateral alveolar mucosal approach to the affected nasal cavity. Aerobic, anaerobic and fungal culture of the cystic contents were negative and histology of the excised tissue was consistent with a benign intranasal epidermoid cyst in each dog. Upper airway obstruction was clinically improved in two dogs. PMID:24697627

  9. Resolution of Allergic Airway Inflammation and Airway Hyperreactivity Is Mediated by IL-17–producing γδT Cells

    PubMed Central

    Murdoch, Jenna R.; Lloyd, Clare M.

    2010-01-01

    Rationale: γδT lymphocytes are enriched within the epithelial microenvironment, where they are thought to maintain homeostasis and limit immunopathology. γδT cells are postulated to exert a regulatory influence during acute allergic airway disease, but the mechanism is unknown. Although regulation of allergic airway disease has been attributed to IL-17–producing T helper (Th) 17 cells, we have found that γδT cells represent the major source of IL-17 in the allergic lung. Objectives: The aim of this study was to determine the contribution of these IL-17–producing γδT cells to regulation of allergic airway inflammation. Methods: Flow cytometry revealed that IL-17–producing γδT cells are more prevalent than IL-17+αβT cells (Th17) in a murine model of ovalbumin-induced allergic inflammation. Measurements and Main Results: Transfer of γδT cells at the peak of acute allergic responses ameliorated airway hyperresponsiveness with a corresponding acceleration in the resolution of eosinophilic and Th2-driven inflammation. Conversely, functional blockade of γδT cells led to exacerbation of injury. Neither treatment changed pulmonary Th17 cell numbers. Moreover, transfer of Th17 cells had no effect on disease outcome. Importantly, IL-17–deficient γδT cells were unable to promote resolution of injury. These data identify IL-17–producing γδT cells as key regulators of the allergic response in vivo. Conclusions: This unfolds a new perspective for the understanding of γδT cell function with regard to innate regulation of the adaptive immune responses, emphasizing that resolution of responses are important in determining the outcome of acute inflammatory episodes as well as for maintenance of tissue integrity and homeostasis. PMID:20413629

  10. Airway Hyperresponsiveness in Asthma Model Occurs Independently of Secretion of β1 Integrins in Airway Wall and Focal Adhesions Proteins Down Regulation.

    PubMed

    Álvarez-Santos, Mayra; Carbajal, Verónica; Tellez-Jiménez, Olivia; Martínez-Cordero, Erasmo; Ruiz, Victor; Hernández-Pando, Rogelio; Lascurain, Ricardo; Santibañez-Salgado, Alfredo; Bazan-Perkins, Blanca

    2016-10-01

    The extracellular domains of some membrane proteins can be shed from the cell. A similar phenomenon occurs with β1 integrins (α1β1 and α2β1) in guinea pig. The putative role of β1 integrin subunit alterations due to shedding in airway smooth muscle (ASM) in an allergic asthma model was evaluated. Guinea pigs were sensitized and challenged with antigen. Antigenic challenges induced bronchoobstruction and hyperresponsiveness at the third antigenic challenge. Immunohistochemistry and immunoelectronmicroscopy studies showed that the cytosolic and extracellular domains of the β1 integrin subunit shared the same distribution in airway structures in both groups. Various polypeptides with similar molecular weights were detected with both the cytosolic and extracellular β1 integrin subunit antibodies in isolated airway myocytes and the connective tissue that surrounds the ASM bundle. Flow cytometry and Western blot studies showed that the expression of cytosolic and extracellular β1 integrin subunit domains in ASM was similar between groups. An increment of ITGB1 mRNA in ASM was observed in the asthma model group. RACE-PCR of ITGB1 in ASM did not show splicing variants. The expression levels of integrin-linked kinase (ILK) and paxillin diminished in the asthma model, but not talin. The levels of phosphorylation of myosin phosphatase target subunit 1 (MYPT1) at Thr(696) increased in asthma model. Our work suggests that β1 integrin is secreted in guinea pig airway wall. This secretion is not altered in asthma model; nevertheless, β1 integrin cytodomain assembly proteins in focal cell adhesions in which ILK and paxillin are involved are altered in asthma model. J. Cell. Biochem. 117: 2385-2396, 2016. © 2016 Wiley Periodicals, Inc. PMID:26969873

  11. Functional effects of KCNQ K+ channels in airway smooth muscle

    PubMed Central

    Evseev, Alexey I.; Semenov, Iurii; Archer, Crystal R.; Medina, Jorge L.; Dube, Peter H.; Shapiro, Mark S.; Brenner, Robert

    2013-01-01

    KCNQ (Kv7) channels underlie a voltage-gated K+ current best known for control of neuronal excitability, and its inhibition by Gq/11-coupled, muscarinic signaling. Studies have indicated expression of KCNQ channels in airway smooth muscle (ASM), a tissue that is predominantly regulated by muscarinic receptor signaling. Therefore, we investigated the function of KCNQ channels in rodent ASM and their interplay with Gq/11-coupled M3 muscarinic receptors. Perforated-patch clamp of dissociated ASM cells detected a K+ current inhibited by the KCNQ antagonist, XE991, and augmented by the specific agonist, flupirtine. KCNQ channels begin to activate at voltages near resting potentials for ASM cells, and indeed XE991 depolarized resting membrane potentials. Muscarinic receptor activation inhibited KCNQ current weakly (~20%) at concentrations half-maximal for contractions. Thus, we were surprised to see that KCNQ had no affect on membrane voltage or muscle contractility following muscarinic activation. Further, M3 receptor-specific antagonist J104129 fumarate alone did not reveal KCNQ effects on muscarinic evoked depolarization or contractility. However, a role for KCNQ channels was revealed when BK-K+ channel activities are reduced. While KCNQ channels do control resting potentials, they appear to play a redundant role with BK calcium-activated K+ channels during ASM muscarinic signaling. In contrast to effect of antagonist, we observe that KCNQ agonist flupirtine caused a significant hyperpolarization and reduced contraction in vitro irrespective of muscarinic activation. Using non-invasive whole animal plethysmography, the clinically approved KCNQ agonist retigabine caused a transient reduction in indexes of airway resistance in both wild type and BK β1 knockout (KO) mice treated with the muscarinic agonist. These findings indicate that KCNQ channels can be recruited via agonists to oppose muscarinic evoked contractions and may be of therapeutic value as bronchodilators

  12. Functional effects of KCNQ K(+) channels in airway smooth muscle.

    PubMed

    Evseev, Alexey I; Semenov, Iurii; Archer, Crystal R; Medina, Jorge L; Dube, Peter H; Shapiro, Mark S; Brenner, Robert

    2013-01-01

    KCNQ (Kv7) channels underlie a voltage-gated K(+) current best known for control of neuronal excitability, and its inhibition by Gq/11-coupled, muscarinic signaling. Studies have indicated expression of KCNQ channels in airway smooth muscle (ASM), a tissue that is predominantly regulated by muscarinic receptor signaling. Therefore, we investigated the function of KCNQ channels in rodent ASM and their interplay with Gq/11-coupled M3 muscarinic receptors. Perforated-patch clamp of dissociated ASM cells detected a K(+) current inhibited by the KCNQ antagonist, XE991, and augmented by the specific agonist, flupirtine. KCNQ channels begin to activate at voltages near resting potentials for ASM cells, and indeed XE991 depolarized resting membrane potentials. Muscarinic receptor activation inhibited KCNQ current weakly (~20%) at concentrations half-maximal for contractions. Thus, we were surprised to see that KCNQ had no affect on membrane voltage or muscle contractility following muscarinic activation. Further, M3 receptor-specific antagonist J104129 fumarate alone did not reveal KCNQ effects on muscarinic evoked depolarization or contractility. However, a role for KCNQ channels was revealed when BK-K(+) channel activities are reduced. While KCNQ channels do control resting potentials, they appear to play a redundant role with BK calcium-activated K(+) channels during ASM muscarinic signaling. In contrast to effect of antagonist, we observe that KCNQ agonist flupirtine caused a significant hyperpolarization and reduced contraction in vitro irrespective of muscarinic activation. Using non-invasive whole animal plethysmography, the clinically approved KCNQ agonist retigabine caused a transient reduction in indexes of airway resistance in both wild type and BK β1 knockout (KO) mice treated with the muscarinic agonist. These findings indicate that KCNQ channels can be recruited via agonists to oppose muscarinic evoked contractions and may be of therapeutic value as

  13. 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

  14. Airway acidification initiates host defense abnormalities in cystic fibrosis mice

    PubMed Central

    Shah, Viral S.; Meyerholz, David K.; Tang, Xiao Xiao; Reznikov, Leah; Alaiwa, Mahmoud Abou; Ernst, Sarah E.; Karp, Philip H.; Wohlford-Lenane, Christine L.; Heilmann, Kristopher P.; Leidinger, Mariah R.; Allen, Patrick D.; Zabner, Joseph; McCray, Paul B.; Ostedgaard, Lynda S.; Stoltz, David A.; Randak, Christoph O.; Welsh, Michael J.

    2016-01-01

    Cystic fibrosis (CF) is caused by mutations in the gene that encodes the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel. In humans and pigs, the loss of CFTR impairs respiratory host defenses, causing airway infection. But CF mice are spared. We found that in all three species, CFTR secreted bicarbonate into airway surface liquid. In humans and pigs lacking CFTR, unchecked H+ secretion by the nongastric H+/K+ adenosine triphosphatase (ATP12A) acidified airway surface liquid, which impaired airway host defenses. In contrast, mouse airways expressed little ATP12A and secreted minimal H+; consequently, airway surface liquid in CF and non-CF mice had similar pH. Inhibiting ATP12A reversed host defense abnormalities in human and pig airways. Conversely, expressing ATP12A in CF mouse airways acidified airway surface liquid, impaired defenses, and increased airway bacteria. These findings help explain why CF mice are protected from infection and nominate ATP12A as a potential therapeutic target for CF. PMID:26823428

  15. Airway acidification initiates host defense abnormalities in cystic fibrosis mice.

    PubMed

    Shah, Viral S; Meyerholz, David K; Tang, Xiao Xiao; Reznikov, Leah; Abou Alaiwa, Mahmoud; Ernst, Sarah E; Karp, Philip H; Wohlford-Lenane, Christine L; Heilmann, Kristopher P; Leidinger, Mariah R; Allen, Patrick D; Zabner, Joseph; McCray, Paul B; Ostedgaard, Lynda S; Stoltz, David A; Randak, Christoph O; Welsh, Michael J

    2016-01-29

    Cystic fibrosis (CF) is caused by mutations in the gene that encodes the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel. In humans and pigs, the loss of CFTR impairs respiratory host defenses, causing airway infection. But CF mice are spared. We found that in all three species, CFTR secreted bicarbonate into airway surface liquid. In humans and pigs lacking CFTR, unchecked H(+) secretion by the nongastric H(+)/K(+) adenosine triphosphatase (ATP12A) acidified airway surface liquid, which impaired airway host defenses. In contrast, mouse airways expressed little ATP12A and secreted minimal H(+); consequently, airway surface liquid in CF and non-CF mice had similar pH. Inhibiting ATP12A reversed host defense abnormalities in human and pig airways. Conversely, expressing ATP12A in CF mouse airways acidified airway surface liquid, impaired defenses, and increased airway bacteria. These findings help explain why CF mice are protected from infection and nominate ATP12A as a potential therapeutic target for CF. PMID:26823428

  16. Dynamics of Surfactant Liquid Plugs at Bifurcating Lung Airway Models

    NASA Astrophysics Data System (ADS)

    Tavana, Hossein

    2013-11-01

    A surfactant liquid plug forms in the trachea during surfactant replacement therapy (SRT) of premature babies. Under air pressure, the plug propagates downstream and continuously divides into smaller daughter plugs at continuously branching lung airways. Propagating plugs deposit a thin film on airway walls to reduce surface tension and facilitate breathing. The effectiveness of SRT greatly depends on the final distribution of instilled surfactant within airways. To understand this process, we investigate dynamics of splitting of surfactant plugs in engineered bifurcating airway models. A liquid plug is instilled in the parent tube to propagate and split at the bifurcation. A split ratio, R, is defined as the ratio of daughter plug lengths in the top and bottom daughter airway tubes and studied as a function of the 3D orientation of airways and different flow conditions. For a given Capillary number (Ca), orienting airways farther away from a horizontal position reduced R due to the flow of a larger volume into the gravitationally favored daughter airway. At each orientation, R increased with 0.0005 < Ca < 0.05. This effect diminished by decrease in airways diameter. This approach will help elucidate surfactant distribution in airways and develop effective SRT strategies.

  17. 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

  18. 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

  19. Thuja orientalis reduces airway inflammation in ovalbumin-induced allergic asthma.

    PubMed

    Shin, In-Sik; Shin, Na-Rae; Jeon, Chan-Mi; Kwon, Ok-Kyoung; Hong, Ju-Mi; Kim, Hui-Seong; Oh, Sei-Ryang; Ahn, Kyung-Seop

    2015-09-01

    Thuja orientalis (TO) may be used as a herbal remedy for the treatment of numerous inflammatory diseases. In the present study, the effects of TO were evaluated on airway inflammation in ovalbumin (OVA)‑induced allergic asthma and RAW264.7 murine macrophage cells. The effects of TO on the production of proinflammatory mediators, were determined in RAW264.7 cells that had been stimulated with lipopolysaccharide (LPS). Furthermore, an in vivo experiment was performed on mice that were sensitized to OVA and then received an OVA airway challenge. TO was administered by daily oral gavage at a dose of 30 mg/kg, 21‑23 days after the initial OVA sensitization. TO was shown to reduce nitric oxide production and reduce the relative mRNA expression levels of inducible nitric oxide synthase (iNOS), interleukin (IL)‑6, cyclooxygenase‑2, matrix metalloproteinase (MMP)‑9, and tumor necrosis factor‑α in RAW264.7 cells stimulated with LPS. In addition, TO markedly decreased the inflammatory cell counts in bronchial alveolar lavage fluid, reduced the levels of IL‑4, IL‑5, IL‑13, eotaxin and immunoglobulin E, and reduced airway hyperresponsivenes, in the OVA sensitized mice. Furthermore, TO attenuated airway inflammation and mucus hypersecretion, induced by the OVA challenge of the lung tissue. TO also reduced the expression of iNOS and MMP‑9 in lung tissue. In conclusion, TO exerted anti‑inflammatory effects in an OVA‑induced allergic asthma model, and in LPS‑stimulated RAW264.7 cells. These results suggest that TO may be a useful therapeutic agent for the treatment of inflammatory diseases, including allergic asthma. PMID:26063078

  20. Low-dose oral cadmium increases airway reactivity and lung neuronal gene expression in mice.

    PubMed

    Chandler, Joshua D; Wongtrakool, Cherry; Banton, Sophia A; Li, Shuzhao; Orr, Michael L; Barr, Dana Boyd; Neujahr, David C; Sutliff, Roy L; Go, Young-Mi; Jones, Dean P

    2016-07-01

    Inhalation of cadmium (Cd) is associated with lung diseases, but less is known concerning pulmonary effects of Cd found in the diet. Cd has a decades-long half-life in humans and significant bioaccumulation occurs with chronic dietary intake. We exposed mice to low-dose CdCl2 (10 mg/L in drinking water) for 20 weeks, which increased lung Cd to a level similar to that of nonoccupationally exposed adult humans. Cd-treated mice had increased airway hyperresponsiveness to methacholine challenge, and gene expression array showed that Cd altered the abundance of 443 mRNA transcripts in mouse lung. In contrast to higher doses, low-dose Cd did not elicit increased metallothionein transcripts in lung. To identify pathways most affected by Cd, gene set enrichment of transcripts was analyzed. Results showed that major inducible targets of low-dose Cd were neuronal receptors represented by enriched olfactory, glutamatergic, cholinergic, and serotonergic gene sets. Olfactory receptors regulate chemosensory function and airway hypersensitivity, and these gene sets were the most enriched. Targeted metabolomics analysis showed that Cd treatment also increased metabolites in pathways of glutamatergic (glutamate), serotonergic (tryptophan), cholinergic (choline), and catecholaminergic (tyrosine) receptors in the lung tissue. Protein abundance measurements showed that the glutamate receptor GRIN2A was increased in mouse lung tissue. Together, these results show that in mice, oral low-dose Cd increased lung Cd to levels comparable to humans, increased airway hyperresponsiveness and disrupted neuronal pathways regulating bronchial tone. Therefore, dietary Cd may promote or worsen airway hyperresponsiveness in multiple lung diseases including asthma. PMID:27401458

  1. Radiology-guided forceps biopsy and airway stenting in severe airway stenosis

    PubMed Central

    Li, Zong-Ming; Wu, Gang; Han, Xin-Wei; Ren, Ke-Wei; Zhu, Ming

    2014-01-01

    PURPOSE We aimed to determine the feasibility, safety, and effectiveness of radiology-guided forceps biopsy and airway stenting in patients with severe airway stenosis. MATERIALS AND METHODS This study involved 28 patients with severe airway stenosis who underwent forceps biopsy between October 2006 and September 2011. Chest multislice computed tomography was used to determine the location and extent of stenosis. Sixteen patients had tracheal stenosis, two patients had stenosis of the tracheal carina, six patients had stenosis of the left main bronchus, and four patients had stenosis of the right main bronchus. Forceps biopsy and stenting of the stenosed area were performed under fluoroscopic guidance in digital subtraction angiography and the biopsy specimens were analyzed histopathologically. We contacted the patients via phone call and utilized a standardized questionnaire to determine their medical condition during a postoperative three-month follow-up. RESULTS The technical success rate of radiology-guided forceps biopsy was 100%. Biopsy specimens were obtained in all patients. Dyspnea was relieved immediately after stent placement. No serious complications, such as tracheal hemorrhage or perforation, mediastinal emphysema, or asphyxia, occurred. CONCLUSION Radiology-guided forceps biopsy and airway stenting can be used for the emergency treatment of severe airway stenosis. This method appears to be safe and effective, and it may be an alternative therapeutic option in patients who cannot tolerate fiberoptic bronchoscopy. PMID:24808434

  2. Mast cell-cholinergic nerve interaction in mouse airways.

    PubMed

    Weigand, Letitia A; Myers, Allen C; Meeker, Sonya; Undem, Bradley J

    2009-07-01

    We addressed the mechanism by which antigen contracts trachea isolated from actively sensitized mice. Trachea were isolated from mice (C57BL/6J) that had been actively sensitized to ovalbumin (OVA). OVA (10 microg ml(-1)) caused histamine release (approximately total tissue content), and smooth muscle contraction that was rapid in onset and short-lived (t(1/2) < 1 min), reaching approximately 25% of the maximum tissue response. OVA contraction was mimicked by 5-HT, and responses to both OVA and 5-HT were sensitive to 10 microm-ketanserin (5-HT(2) receptor antagonist) and strongly inhibited by atropine (1microm). Epithelial denudation had no effect on the OVA-induced contraction. Histological assessment revealed about five mast cells/tracheal section the vast majority of which contained 5-HT. There were virtually no mast cells in the mast cell-deficient (sash -/-) mouse trachea. OVA failed to elicit histamine release or contractile responses in trachea isolated from sensitized mast cell-deficient (sash -/-) mice. Intracellular recordings of the membrane potential of parasympathetic neurons in mouse tracheal ganglia revealed a ketanserin-sensitive 5-HT-induced depolarization and similar depolarization in response to OVA challenge. These data support the hypothesis that antigen-induced contraction of mouse trachea is epithelium-independent, and requires mast cell-derived 5-HT to activate 5-HT(2) receptors on parasympathetic cholinergic neurons. This leads to acetylcholine release from nerve terminals, and airway smooth muscle contraction. PMID:19403609

  3. Silencing Nociceptor Neurons Reduces Allergic Airway Inflammation.

    PubMed

    Talbot, Sébastien; Abdulnour, Raja-Elie E; Burkett, Patrick R; Lee, Seungkyu; Cronin, Shane J F; Pascal, Maud A; Laedermann, Cedric; Foster, Simmie L; Tran, Johnathan V; Lai, Nicole; Chiu, Isaac M; Ghasemlou, Nader; DiBiase, Matthew; Roberson, David; Von Hehn, Christian; Agac, Busranour; Haworth, Oliver; Seki, Hiroyuki; Penninger, Josef M; Kuchroo, Vijay K; Bean, Bruce P; Levy, Bruce D; Woolf, Clifford J

    2015-07-15

    Lung nociceptors initiate cough and bronchoconstriction. To elucidate if these fibers also contribute to allergic airway inflammation, we stimulated lung nociceptors with capsaicin and observed increased neuropeptide release and immune cell infiltration. In contrast, ablating Nav1.8(+) sensory neurons or silencing them with QX-314, a charged sodium channel inhibitor that enters via large-pore ion channels to specifically block nociceptors, substantially reduced ovalbumin- or house-dust-mite-induced airway inflammation and bronchial hyperresponsiveness. We also discovered that IL-5, a cytokine produced by activated immune cells, acts directly on nociceptors to induce the release of vasoactive intestinal peptide (VIP). VIP then stimulates CD4(+) and resident innate lymphoid type 2 cells, creating an inflammatory signaling loop that promotes allergic inflammation. Our results indicate that nociceptors amplify pathological adaptive immune responses and that silencing these neurons with QX-314 interrupts this neuro-immune interplay, revealing a potential new therapeutic strategy for asthma. PMID:26119026

  4. Anesthetic management of laser airway surgery.

    PubMed

    Spiess, B D; Ivankovich, A D

    1990-01-01

    This brief review of the anesthesiologist's role in the team effort necessary for the safe treatment of airway tumors by laser beam is provided to acquaint the referring physician or medical oncologist with some of the anesthesiologist's operating room concerns and how they are met. The necessity of bringing the patient to a level of maximum physiologic reserve prior to treatment becomes obvious with information gained by scanning this review. The referring physician or medical oncologist aids the patient and the anesthesiologist and surgeon by performing a thorough preoperative cardiopulmonary evaluation and therapeutic intervention, as indicated by patient need. The review includes a description of the actions of the carbon dioxide (CO2) and neodynium-yttrium aluminum garnet (YAG) lasers, "laser safety" for patients and personnel, monitoring, guarding the airway, ignition dangers, and comments on the use of jet and high frequency jet ventilation (HFJV). PMID:2111934

  5. Genetic differences in airway smooth muscle function.

    PubMed

    Martin, James G; Jo, Taisuke

    2008-01-01

    The genetic basis for airway smooth muscle properties is poorly explored. Contraction and relaxation are altered in asthmatic airway smooth muscle, but the basis for the alterations and the role that muscle-specific susceptibility genes may play is largely unexplored. Alterations in the beta-adrenergic receptor, signaling pathways affecting inositol phosphate metabolism, adenylyl and guanylyl cyclase activity, and contractile proteins such as the myosin heavy chain are all suggested by experimental model systems. Significant changes in proliferative and secretory capacities of asthmatic smooth muscle are also demonstrated, but their genetic basis also requires elucidation. Certain asthma-related genes such as ADAM33, although potentially important for smooth muscle function, have been incompletely explored. PMID:18094088

  6. Endoscopic high-resolution auto fluorescence imaging and optical coherence tomography of airways in vivo (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Pahlevaninezhad, Hamid; Lee, Anthony; Hohert, Geoffrey; Schwartz, Carley; Shaipanich, Tawimas; Ritchie, Alexander J.; Zhang, Wei; MacAulay, Calum E.; Lam, Stephen; Lane, Pierre M.

    2016-03-01

    In this work, we present multimodal imaging of peripheral airways in vivo using an endoscopic imaging system capable of co-registered optical coherence tomography and autofluorescence imaging (OCT-AFI). This system employs a 0.9 mm diameter double-clad fiber optic-based catheter for endoscopic imaging of small peripheral airways. Optical coherence tomography (OCT) can visualize detailed airway morphology in the lung periphery and autofluorescence imaging (AFI) can visualize fluorescent tissue components such as collagen and elastin, improving the detection of airway lesions. Results from in vivo imaging of 40 patients indicate that OCT and AFI offer complementary information that may increase the ability to identify pulmonary nodules in the lung periphery and improve the safety of biopsy collection by identifying large blood vessels. AFI can rapidly visualize in vivo vascular networks using fast scanning parameters resulting in vascular-sensitive imaging with less breathing/cardiac motion artifacts compared to Doppler OCT imaging. By providing complementary information about structure and function of tissue, OCT-AFI may improve site selection during biopsy collection in the lung periphery.

  7. Distending Pressure Did Not Activate Acute Phase or Inflammatory Responses in the Airways and Lungs of Fetal, Preterm Lambs

    PubMed Central

    Petersen, Rebecca Y.; Royse, Emily; Kemp, Matthew W.; Miura, Yuichiro; Noe, Andres; Jobe, Alan H.; Hillman, Noah H.

    2016-01-01

    Background Mechanical ventilation at birth causes airway injury and lung inflammation in preterm sheep. Continuous positive airway pressure (CPAP) is being increasingly used clinically to transition preterm infants at birth. Objective To test if distending pressures will activate acute phase reactants and inflammatory changes in the airways of fetal, preterm lambs. Methods The head and chest of fetal lambs at 128±1 day GA were surgically exteriorized. With placental circulation intact, fetal lambs were then randomized to one of five 15 minute interventions: PEEP of 0, 4, 8, 12, or 16 cmH2O. Recruitment volumes were recorded. Fetal lambs remained on placental support for 30 min after the intervention. The twins of each 0 cmH2O animal served as controls. Fetal lung fluid (FLF), bronchoalveolar lavage fluid (BAL), right mainstem bronchi and peripheral lung tissue were evaluated for inflammation. Results Recruitment volume increased from 0.4±0.04 mL/kg at 4 cmH2O to 2.4±0.3 mL/kg at 16 cmH2O. The lambs were surfactant deficient, and all pressures were below the opening inflection pressure on pressure-volume curve. mRNA expression of early response genes and pro-inflammatory cytokines did not increase in airway tissue or lung tissue at any pressure compared to controls. FLF and BAL also did not have increases in early response proteins. No histologic changes or Egr-1 activation was present at the pressures used. Conclusion Distending pressures as high as 16 cmH2O did not recruit lung volume at birth and did not increase markers of injury in the lung or airways in non-breathing preterm fetal sheep. PMID:27463520

  8. Airway hyperreactivity elicited by toluene diisocyanate (TDI)-albumin conjugate is not accompanied by airway eosinophilic infiltration in guinea pigs.

    PubMed

    Huang, J; Millecchia, L L; Frazer, D G; Fedan, J S

    1998-02-01

    Nonspecific airway hyperresponsiveness is present in many patients with toluene diisocyanate (TDI)-induced asthma; however, the underlying pathophysiological mechanisms of this hyperresponsiveness remain controversial. In the present study, we used a guinea pig model to investigate the association of TDI-induced airway hyperresponsiveness with eosinophilic airway infiltration, which is widely considered to play a key role in the development of allergen-induced hyperresponsiveness. Guinea pigs were sensitized by i.d. injections of 10 microl TDI on day 1 and day 6. Control animals received saline injections. Two weeks after the second injection, airway reactivity to inhaled methacholine and specific airway resistance (sRaw) was measured before and at several times after inhalation challenge with TDI-GSA (guinea pig serum albumin) conjugates. Eosinophils in the airways were detected using enzyme histochemistry and quantified using computer-assisted image analysis. TDI-specific IgG1 antibodies were found in the blood of TDI-sensitized animals. An immediate increase in sRaw was induced in these animals by TDI-GSA challenge; airway hyperresponsiveness to methacholine was observed at 6 h and 18 h after TDI-GSA challenge. However, TDI-GSA challenge did not result in an elevation of eosinophils in the airways, compared with control animals. The results suggest that the development of TDI-induced airway hyperresponsiveness is not dependent upon eosinophil infiltration in airways. PMID:9520137

  9. Airway obstruction by an unexpected equipment damage.

    PubMed

    Schober, Patrick; Loer, Stephan A; Schwarte, Lothar A

    2016-08-01

    Intubating introducers are often used to facilitate difficult endotracheal intubation. We report a case in which a Frova catheter was used for insertion of a laser-resistant endotracheal tube and in which a strip of plastic was shaved off from the catheter. The plastic strip formed a convolute mass, causing relevant airway obstruction. Clinicians should be aware of this potentially dangerous complication and should be cautious in using Frova intubating introducers in combination with laser-resistant tubes. PMID:27290946

  10. Reactive airways dysfunction syndrome: two case reports.

    PubMed

    Tabar, A I; Alvarez, M J; Acero, S; Olaguíbel, J M; García, B E; Quirce, S

    1998-01-01

    Reactive airways dysfunction syndrome (RADS) is a type of asthma that develops in subjects without prior pulmonary disease, following single or multiple exposure to high levels of nonimmunogenic irritants. The main difference from classic occupational asthma is the absence of a latency period. Non-specific bronchial hyperresponsiveness is characteristic of the disease and usually persists after cessation of exposure. We report the cases of two subjects in whom RADS developed after occupational exposure to irritants. PMID:9615307

  11. 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

  12. Year in review 2014: airway clearance.

    PubMed

    Strickland, Shawna L

    2015-04-01

    The respiratory therapist has had integrated adjuncts to improve mucus clearance for decades. However, there is a lack of literature describing the impact of these interventions on specific patient populations, resulting in an inability to make recommendations about the use of devices and techniques. The purpose of this article is to review recent literature regarding airway clearance therapies in a manner that is most likely to have interest to the readers of Respiratory Care. PMID:25784773

  13. Cardiac arrest equipment to support airway.

    PubMed

    Aldridge, Matthew; Jevon, Phil

    Each hospital should have standardised cardiac arrest trolleys equipped with all the instruments and medication needed to deal with an acute adult cardiac arrest. Nurses must know the contents of these trolleys and how to use them to fulfil their common role as first responder. This first article in a two-part series looks at equipment to aid airway management and breathing; part two will focus on circulation. PMID:25174131

  14. 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

  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. 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

  17. Surgery of the airway: historic notes

    PubMed Central

    2016-01-01

    Prior to the 20th century, the need for surgical procedures on the airway was infrequent and consisted mainly of tracheostomy to relieve airway obstruction or repair of tracheal injuries such as lacerations. Even the ability of tracheal suture lines to heal primarily was viewed with concern due to the rigidity of the tracheal wall, its precarious blood supply and uncertainty as to whether the cartilage components could heal without complications. In the 20th century the evolution of tracheal procedures on major airways evolved to meet the challenges provided by the expanding fields of thoracic surgery and advent of mechanical respiratory support with its associated complications. In the first half of the century lobar and lung resections done for tuberculosis and lung cancer required methods for safe closure of the resulting bronchial stumps and end-to-end bronchial anastomosis in the case of sleeve resections of the lung. Beginning in mid-century the advent of respiratory care units for the treatment of polio and for the expanding fields of thoracic and cardiac surgery resulted in a significant number of post-intubation tracheal stenosis requiring resection and primary repair. In the last 20 years of the century the development of lung transplantation with its requirement for successful bronchial anastomoses between the donor and recipient bronchi, created unique challenges including ischemia of the donor bronchus the adverse effects of immunosuppression, donor lung preservation and diagnosis and management of post-transplant infection and rejection. PMID:26981261

  18. Voxel classification based airway tree segmentation

    NASA Astrophysics Data System (ADS)

    Lo, Pechin; de Bruijne, Marleen

    2008-03-01

    This paper presents a voxel classification based method for segmenting the human airway tree in volumetric computed tomography (CT) images. In contrast to standard methods that use only voxel intensities, our method uses a more complex appearance model based on a set of local image appearance features and Kth nearest neighbor (KNN) classification. The optimal set of features for classification is selected automatically from a large set of features describing the local image structure at several scales. The use of multiple features enables the appearance model to differentiate between airway tree voxels and other voxels of similar intensities in the lung, thus making the segmentation robust to pathologies such as emphysema. The classifier is trained on imperfect segmentations that can easily be obtained using region growing with a manual threshold selection. Experiments show that the proposed method results in a more robust segmentation that can grow into the smaller airway branches without leaking into emphysematous areas, and is able to segment many branches that are not present in the training set.

  19. Spontaneous intrathyroidal hematoma causing airway obstruction

    PubMed Central

    Best, Corliss A.E.; Dhaliwal, Sandeep; Tam, Samantha; Low, T. Hubert; Hughes, Brian; Fung, Kevin; MacNeil, S. Danielle

    2016-01-01

    Abstract Introduction: Spontaneous thyroid hemorrhage is a rare occurrence that results in pain, discomfort, and occasionally compressive symptoms. Infrequently, extensive thyroid hemorrhage can result in a rapidly expanding hematoma resulting in airway compromise. This is a case of an otherwise healthy young woman, 3 months postpartum, with a slowly expanding spontaneous thyroid hemorrhage that measured at 7 × 5.5 × 5 cm by computed tomography. She ultimately required intubation to manage respiratory distress and subsequently a hemithyroidectomy for definitive treatment. The case presentation is followed by a literature review where known etiologies of thyroid hematoma including traumatic and nontraumatic causes, precipitating anticoagulation, and spontaneous rupture of branches of the external carotid artery are outlined. The potential links to pregnancy are explored. The roles of bedside thyroid ultrasound in the emergency department and lateral neck roentgenogram in diagnosis are explored. The importance of airway management and indications for conservative versus surgical treatments are discussed. Conclusions: This is a case of a spontaneous intrathyroidal hemorrhage, which progressed over days to ultimately cause airway compromise. It is imperative that physicians are educated on the appropriate detection and management of the potentially life-threatening spontaneous thyroid hematoma. PMID:27583841

  20. The buffer capacity of airway epithelial secretions

    PubMed Central

    Kim, Dusik; Liao, Jie; Hanrahan, John W.

    2014-01-01

    The pH of airway epithelial secretions influences bacterial killing and mucus properties and is reduced by acidic pollutants, gastric reflux, and respiratory diseases such as cystic fibrosis (CF). The effect of acute acid loads depends on buffer capacity, however the buffering of airway secretions has not been well characterized. In this work we develop a method for titrating micro-scale (30 μl) volumes and use it to study fluid secreted by the human airway epithelial cell line Calu-3, a widely used model for submucosal gland serous cells. Microtitration curves revealed that HCO−3 is the major buffer. Peak buffer capacity (β) increased from 17 to 28 mM/pH during forskolin stimulation, and was reduced by >50% in fluid secreted by cystic fibrosis transmembrane conductance regulator (CFTR)-deficient Calu-3 monolayers, confirming an important role of CFTR in HCO−3 secretion. Back-titration with NaOH revealed non-volatile buffer capacity due to proteins synthesized and released by the epithelial cells. Lysozyme and mucin concentrations were too low to buffer Calu-3 fluid significantly, however model titrations of porcine gastric mucins at concentrations near the sol-gel transition suggest that mucins may contribute to the buffer capacity of ASL in vivo. We conclude that CFTR-dependent HCO−3 secretion and epithelially-derived proteins are the predominant buffers in Calu-3 secretions. PMID:24917822

  1. 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

  2. The laryngeal mask airway in obstetrical anaesthesia.

    PubMed

    Gataure, P S; Hughes, J A

    1995-02-01

    The laryngeal mask airway (LMA) has been used extensively to provide a safe airway in spontaneously breathing patients who are not at risk from aspiration of gastric contents. The role of the LMA in the event of a failed intubation in an obstetrical patient, and its place in a failed intubation drill remains unclear. Two hundred and fifty consultant obstetric anaesthetists in the United Kingdom were asked to complete an anonymous questionnaire regarding their views about using the laryngeal mask airway (LMA) in obstetrical anaesthesia. The LMA was available in 91.4% of obstetric units. Seventy-two per cent of anaesthetists were in favour