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Sample records for distal airway nitric

  1. Nitric oxide in the airways.

    PubMed

    Scadding, Glenis

    2007-08-01

    This review briefly explains the basic facts about nitric oxide, which is entering clinical practice as a measure of lower airways inflammation and is likely also to be employed in otorhinolaryngological practice. These include the validity of nasal nitric oxide in diagnosing primary ciliary dyskinesia and in monitoring the response to chronic rhinosinusitis therapy. The nasal nitric oxide value combined with a humming manoeuvre, which increases the passage of nitric oxide from the sinuses to the nose if the ostiomeatal complex is patent, could reduce the need for computed tomography scans. The link between nitric oxide production and ciliary beating requires further exploration. Therapeutic adjustments to nitric oxide production are under investigation. Nitric oxide is likely to prove highly relevant to airways defence, as well as being an inflammatory mediator. Nasal nitric oxide probably explains some of the benefit of nasal rather than mouth breathing.

  2. Nitric oxide and airway reactivity.

    PubMed

    Strapkova, A; Nosalova, G

    2001-01-01

    Nitric oxide is a neurotransmitter of the inhibitory nonadrenergic noncholinergic mediation in the respiratory system. Its participation in the regulation of airways functions is determined by its level in the organism. We examined participation of nitric oxide in the changes of the airway reactivity evoked by toluene exposure as the source of the free radicals. The changes of nitric oxide level in the organism were evoked by administration of its indirect donor isosorbide dinitrate. Thiol groups were provided by administration of antioxidative mucolytic N-acetylcysteine. Used drugs--isosorbide dinitrate (5 mg/kg b.w.) and N-acetylcysteine (300 mg/kg b.w.) were administered intraperitoneally or by inhalation 30 minutes before each exposure to the toluene vapours. The control group was not treated with drugs. After toluene exposure (2 hours in each of 3 consecutive days) tracheal and lung strips smooth muscle reactivity to histamine was observed under in "in vitro" conditions. The administration of isosorbide dinitrate decreased especially the lung strip smooth muscle reactivity to histamine. We revealed more expressive effect of the pretreatment with intraperitoneally administered isosorbide dinitrate in the comparison with inhalation. Simultaneous pretreatment with N-acetylcysteine intensified beneficial effect of isosorbide dinitrate probably by increasing of the intracellullary level of thiols. In our experimental conditions possible participation of nitric oxide in changes of airways smooth muscle reactivity after exposure to the toluene follows from results, as well as the importance of thiol groups for the activity of its indirect donors. (Fig. 6, Tab. 3, Ref. 35.)

  3. The effect of body weight on distal airway function and airway inflammation.

    PubMed

    van de Kant, Kim D G; Paredi, Paolo; Meah, Sally; Kalsi, Harpal S; Barnes, Peter J; Usmani, Omar S

    Obesity is a global health problem that adversely influences the respiratory system. We assessed the effects of body mass index (BMI) on distal airway function and airway inflammation. Impulse oscillometry (IOS) as a measure of distal airway function, together with spirometry, were assessed in adults with a range of different BMIs. Airway inflammation was assessed with the fraction of exhaled nitric oxide (FeNO) and participants exhaled at various exhalation flows to determine alveolar and bronchial NO. In total 34 subjects were enrolled in the study; 19 subjects had a normal BMI (18.50-24.99), whilst 15 subjects were overweight (BMI 25.00-29.99), or obese (BMI ≥30). All subjects had normal spirometry. However, IOS measures of airway resistance (R) at 5Hz, 20Hz and frequency dependence (R5-20) were elevated in overweight/obese individuals, compared to subjects with a normal BMI (median (interquartile range)); 5Hz: 0.41 (0.37, 0.45) vs. 0.32 (0.30, 0.37)kPa/l/s; 20Hz: 0.34 (0.30, 0.37) vs. 0.30 (0.26, 0.33)kPa/l/s; R5-20: 0.06 (0.04, 0.11) vs. 0.03 (0.01, 0.05)kPa/l/s; p<0.05), whereas airway reactance at 20Hz was decreased in overweight/obese individuals (20Hz: 0.07 (0.03, 0.09) vs. 0.10 (0.07, 0.13)kPa/l/s, p=0.009; 5Hz: -0.12 (-0.15, -0.10) vs. -0.10 (-0.13, -0.09)kPa/l/s, p=0.07). In contrast, within-breath IOS measures (a sign of expiratory flow limitation) and FeNO inflammatory measures, did not differ between groups (p>0.05). Being overweight has significant effects on distal and central airway function as determined by IOS, which is not detected by spirometry. Obesity does not influence airway inflammation as measured by FeNO. IOS is a reliable technique to identify airway abnormalities in the presence of normal spirometry in overweight people. Copyright © 2015 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

  4. Distal airway dysfunction identifies pulmonary inflammation in asymptomatic smokers.

    PubMed

    Berger, Kenneth I; Pradhan, Deepak R; Goldring, Roberta M; Oppenheimer, Beno W; Rom, William N; Segal, Leopoldo N

    2016-10-01

    Smoking induced inflammation leads to distal airway destruction. However, the relationship between distal airway dysfunction and inflammation remains unclear, particularly in smokers prior to the development of airway obstruction. Seven normal controls and 16 smokers without chronic obstructive pulmonary disease (COPD) were studied. Respiratory function was assessed using the forced oscillation technique (FOT). Abnormal FOT was defined as elevated resistance at 5 Hz (R5). Parameters reflecting distal lung function included frequency dependence of resistance (R5-20) and dynamic elastance (X5). Inflammation was quantified in concentrated bronchoalveolar lavage utilising cell count differential and cytokines expressed as concentration per mL epithelial lining fluid. All control subjects and seven smokers had normal R5. Nine smokers had elevated R5 with abnormal R5-20 and X5, indicating distal lung dysfunction. The presence of abnormal FOT was associated with two-fold higher lymphocyte and neutrophil counts (p<0.025) and with higher interleukin (IL)-8, eotaxin and fractalkine levels (p<0.01). Reactivity of R5-20 and X5 correlated with levels of IL-8, eotaxin, fractalkine, IL-12p70 and transforming growth factor-α (r>0.47, p<0.01). Distal airway dysfunction in smokers without COPD identifies the presence of distal lung inflammation that parallel reported observations in established COPD. These findings were not evident on routine pulmonary function testing and may allow the identification of smokers at risk of progression to COPD.

  5. Distal airway dysfunction identifies pulmonary inflammation in asymptomatic smokers

    PubMed Central

    Berger, Kenneth I.; Pradhan, Deepak R.; Goldring, Roberta M.; Oppenheimer, Beno W.; Rom, William N.

    2016-01-01

    Smoking induced inflammation leads to distal airway destruction. However, the relationship between distal airway dysfunction and inflammation remains unclear, particularly in smokers prior to the development of airway obstruction. Seven normal controls and 16 smokers without chronic obstructive pulmonary disease (COPD) were studied. Respiratory function was assessed using the forced oscillation technique (FOT). Abnormal FOT was defined as elevated resistance at 5 Hz (R5). Parameters reflecting distal lung function included frequency dependence of resistance (R5–20) and dynamic elastance (X5). Inflammation was quantified in concentrated bronchoalveolar lavage utilising cell count differential and cytokines expressed as concentration per mL epithelial lining fluid. All control subjects and seven smokers had normal R5. Nine smokers had elevated R5 with abnormal R5–20 and X5, indicating distal lung dysfunction. The presence of abnormal FOT was associated with two-fold higher lymphocyte and neutrophil counts (p<0.025) and with higher interleukin (IL)-8, eotaxin and fractalkine levels (p<0.01). Reactivity of R5–20 and X5 correlated with levels of IL-8, eotaxin, fractalkine, IL-12p70 and transforming growth factor-α (r>0.47, p<0.01). Distal airway dysfunction in smokers without COPD identifies the presence of distal lung inflammation that parallel reported observations in established COPD. These findings were not evident on routine pulmonary function testing and may allow the identification of smokers at risk of progression to COPD. PMID:27995132

  6. Host-microbe interactions in distal airways: relevance to chronic airway diseases.

    PubMed

    Martin, Clémence; Burgel, Pierre-Régis; Lepage, Patricia; Andréjak, Claire; de Blic, Jacques; Bourdin, Arnaud; Brouard, Jacques; Chanez, Pascal; Dalphin, Jean-Charles; Deslée, Gaetan; Deschildre, Antoine; Gosset, Philippe; Touqui, Lhousseine; Dusser, Daniel

    2015-03-01

    This article is the summary of a workshop, which took place in November 2013, on the roles of microorganisms in chronic respiratory diseases. Until recently, it was assumed that lower airways were sterile in healthy individuals. However, it has long been acknowledged that microorganisms could be identified in distal airway secretions from patients with various respiratory diseases, including cystic fibrosis (CF) and non-CF bronchiectasis, chronic obstructive pulmonary disease, asthma and other chronic airway diseases (e.g. post-transplantation bronchiolitis obliterans). These microorganisms were sometimes considered as infectious agents that triggered host immune responses and contributed to disease onset and/or progression; alternatively, microorganisms were often considered as colonisers, which were considered unlikely to play roles in disease pathophysiology. These concepts were developed at a time when the identification of microorganisms relied on culture-based methods. Importantly, the majority of microorganisms cannot be cultured using conventional methods, and the use of novel culture-independent methods that rely on the identification of microorganism genomes has revealed that healthy distal airways display a complex flora called the airway microbiota. The present article reviews some aspects of current literature on host-microbe (mostly bacteria and viruses) interactions in healthy and diseased airways, with a special focus on distal airways.

  7. Secretion of acid and base equivalents by intact distal airways.

    PubMed

    Inglis, S K; Wilson, S M; Olver, R E

    2003-05-01

    Secretion of HCO(3)(-) by airway submucosal glands is essential for normal liquid and mucus secretion. Because the liquid bathing the airway surface (ASL) is acidic, it has been proposed that the surface epithelium may acidify HCO(3)(-)-rich glandular fluid. The aim of this study was to investigate the mechanisms by which intact distal bronchi, which contain both surface and glandular epithelium, modify pH of luminal fluid. Distal bronchi were isolated from pig lungs, cannulated in a bath containing HCO(3)(-)-buffered solution, and perfused continually with an aliquot of similar, lightly buffered solution (LBS) in which NaCl replaced NaHCO(3)(-) (pH 7 with NaOH). The pH of this circulating LBS initially acidified (by 0.053 +/- 0.0053 pH units) and transepithelial potential difference (PD) depolarized. The magnitude of acidification was increased when pH(LBS) was higher. This acidification was unaffected by luminal dimethylamiloride (DMA, 100 microM) but was inhibited by 100 nM bafilomycin A(1) (by 76 +/- 13%), suggesting involvement of vacuolar-H(+) ATPase. Addition of ACh (10 microM) evoked alkalinization of luminal LBS and hyperpolarization of transepithelial PD. The alkalinization was inhibited in HCO(3)(-)-free solutions containing acetazolamide (1 mM) and by DMA and was enhanced by bumetanide (100 microM), an inhibitor of Cl(-) secretion. The hyperpolarization was unaffected by these maneuvers. The anion channel blocker 5-nitro-2-(3-phenylpropylamino)benzoate (300 microM) and combined treatment with DMA and bumetanide blocked both the alkalinization and hyperpolarization responses to ACh. These results are consistent with earlier studies showing that ACh evokes glandular secretion of HCO(3)(-) and Cl(-). Isolated distal airways thus secrete both acid and base equivalents.

  8. Anatomy, pathology, and physiology of the tracheobronchial tree: emphasis on the distal airways.

    PubMed

    Hyde, Dallas M; Hamid, Qutayba; Irvin, Charles G

    2009-12-01

    This article covers the airway tree with respect to anatomy, pathology, and physiology. The anatomic portion discusses various primate groups so as to help investigators understand similarities and differences between animal models. An emphasis is on distal airway findings. The pathology section focuses on the inflammatory responses that occur in proximal and distal airways. The physiologic review brings together the anatomic and pathologic components to the functional state and proposes ways to evaluate the small airways in patients with asthma.

  9. Recent Advances on Nitric Oxide in the Upper Airways.

    PubMed

    Maniscalco, Mauro; Bianco, Andrea; Mazzarella, Gennaro; Motta, Andrea

    2016-01-01

    Exhaled nitric oxide (NO) originates from the upper airways, and takes action, to varying extents, in regulation, protection and defense, as well as in noxious processes. Nitric oxide retains important functions in a wide range of physiological and pathophysiological processes of the human body, including vaso-regulation, antimicrobial activity, neurotransmission and respiration. This review article reports the ongoing investigations regarding the source, biology and relevance of NO within upper respiratory tract. In addition, we discuss the role of NO, originating from nasal and paranasal sinuses, in inflammatory disorders such as allergic rhinitis, sinusitis, primary ciliary dyskinesia, and cystic fibrosis.

  10. RSV-encoded NS2 promotes epithelial cell shedding and distal airway obstruction

    PubMed Central

    Liesman, Rachael M.; Buchholz, Ursula J.; Luongo, Cindy L.; Yang, Lijuan; Proia, Alan D.; DeVincenzo, John P.; Collins, Peter L.; Pickles, Raymond J.

    2014-01-01

    Respiratory syncytial virus (RSV) infection is the major cause of bronchiolitis in young children. The factors that contribute to the increased propensity of RSV-induced distal airway disease compared with other commonly encountered respiratory viruses remain unclear. Here, we identified the RSV-encoded nonstructural 2 (NS2) protein as a viral genetic determinant for initiating RSV-induced distal airway obstruction. Infection of human cartilaginous airway epithelium (HAE) and a hamster model of disease with recombinant respiratory viruses revealed that NS2 promotes shedding of infected epithelial cells, resulting in two consequences of virus infection. First, epithelial cell shedding accelerated the reduction of virus titers, presumably by clearing virus-infected cells from airway mucosa. Second, epithelial cells shedding into the narrow-diameter bronchiolar airway lumens resulted in rapid accumulation of detached, pleomorphic epithelial cells, leading to acute distal airway obstruction. Together, these data indicate that RSV infection of the airway epithelium, via the action of NS2, promotes epithelial cell shedding, which not only accelerates viral clearance but also contributes to acute obstruction of the distal airways. Our results identify RSV NS2 as a contributing factor for the enhanced propensity of RSV to cause severe airway disease in young children and suggest NS2 as a potential therapeutic target for reducing the severity of distal airway disease. PMID:24713657

  11. Distal airways in humans: dynamic hyperpolarized 3He MR imaging--feasibility

    NASA Technical Reports Server (NTRS)

    Tooker, Angela C.; Hong, Kwan Soo; McKinstry, Erin L.; Costello, Philip; Jolesz, Ferenc A.; Albert, Mitchell S.

    2003-01-01

    Dynamic hyperpolarized helium 3 (3He) magnetic resonance (MR) imaging of the human airways is achieved by using a fast gradient-echo pulse sequence during inhalation. The resulting dynamic images show differential contrast enhancement of both distal airways and the lung periphery, unlike static hyperpolarized 3He MR images on which only the lung periphery is seen. With this technique, up to seventh-generation airway branching can be visualized. Copyright RSNA, 2003.

  12. Distal airways in humans: dynamic hyperpolarized 3He MR imaging--feasibility

    NASA Technical Reports Server (NTRS)

    Tooker, Angela C.; Hong, Kwan Soo; McKinstry, Erin L.; Costello, Philip; Jolesz, Ferenc A.; Albert, Mitchell S.

    2003-01-01

    Dynamic hyperpolarized helium 3 (3He) magnetic resonance (MR) imaging of the human airways is achieved by using a fast gradient-echo pulse sequence during inhalation. The resulting dynamic images show differential contrast enhancement of both distal airways and the lung periphery, unlike static hyperpolarized 3He MR images on which only the lung periphery is seen. With this technique, up to seventh-generation airway branching can be visualized. Copyright RSNA, 2003.

  13. Hypoxia depresses nitric oxide output in the human nasal airways.

    PubMed

    Haight, J S; Qian, W; Daya, H; Chalmers, P; Zamel, N

    2000-03-01

    The role of oxygen in the nasal air on nasal nitric oxide (NO) output was studied in 13 adult volunteers. Nasal NO was measured while air containing oxygen (0%-100% in nitrogen) was aspirated through the nasal airway before and after the topical application of xylometazoline. The mean nasal NO output of the untreated nose was 507.8 +/- 161.9 nL/min (mean +/- SD) when 21% oxygen was aspirated through the nasal cavities in series and remained unaltered by 100% O2 (P = .79). Below 10% oxygen the reduction in nasal NO output correlated positively and significantly with the decrease in oxygen concentration (r2 = 0.14). NO output was 245.2 +/- 153.4 nL/min at 0% oxygen, a significant decline from 21% oxygen (P < .0001). Nasal vasoconstriction induced by xylometazoline and alterations in the blood oxygen content by a maximal breath-holding or breathing 100% oxygen did not alter nasal NO in hypoxia (P = .41). Nasal NO output is markedly depressed in hypoxia and is oxygen dependent at concentrations of less than 10%. Approximately 50% of nasally generated NO is produced from oxygen in nasal air or regulated by it.

  14. Inducible nitric oxide synthase expression is reduced in cystic fibrosis murine and human airway epithelial cells.

    PubMed Central

    Kelley, T J; Drumm, M L

    1998-01-01

    It has been reported that exhaled nitric oxide levels are reduced in cystic fibrosis (CF) patients. We have examined the inducible isoform of nitric oxide synthase (iNOS) in the airways by immunostaining and found that iNOS is constitutively expressed in the airway epithelia of non-CF mouse and human tissues but essentially absent in the epithelium of CF airways. We explored potential consequences of lost iNOS expression and found that iNOS inhibition significantly increases mouse nasal trans-epithelial potential difference, and hindered the ability of excised mouse lungs to prevent growth of Pseudomonas aeruginosa. The absence of continuous nitric oxide production in epithelial cells of CF airways may play a role in two CF-associated characteristics: hyperabsorption of sodium and susceptibility to bacterial infections. PMID:9739054

  15. Distal airway epithelial progenitor cells are radiosensitive to High-LET radiation

    PubMed Central

    McConnell, Alicia M.; Konda, Bindu; Kirsch, David G.; Stripp, Barry R.

    2016-01-01

    Exposure to high-linear energy transfer (LET) radiation occurs in a variety of situations, including charged particle radiotherapy, radiological accidents, and space travel. However, the extent of normal tissue injury in the lungs following high-LET radiation exposure is unknown. Here we show that exposure to high-LET radiation led to a prolonged loss of in vitro colony forming ability by airway epithelial progenitor cells. Furthermore, exposure to high-LET radiation induced clonal expansion of a subset of progenitor cells in the distal airway epithelium. Clonal expansion following high-LET radiation exposure was correlated with elevated progenitor cell apoptosis, persistent γ-H2AX foci, and defects in mitotic progression of distal airway progenitors. We discovered that the effects of high-LET radiation exposure on progenitor cells occur in a p53-dependent manner. These data show that high-LET radiation depletes the distal airway progenitor pool by inducing cell death and loss of progenitor function, leading to clonal expansion. Importantly, high-LET radiation induces greater long-term damage to normal lung tissue than the relative equivalent dose of low-LET γ-rays, which has implications in therapeutic development and risk assessment. PMID:27659946

  16. [Environmental causes of the distal airways disease. Hypersensitivity pneumonitis and rare causes].

    PubMed

    Dalphin, J-C; Didier, A

    2013-10-01

    Hypersensitivity pneumonitis is one of the most frequent causes of distal airways disease. It is associated with inflammation of the bronchioles, predominantly by lymphocytic infiltrates, and with granuloma formation causing bronchial obstruction. This inflammation explains the clinical manifestations and the airways obstruction seen on pulmonary function tests, most often in the distal airways but proximal in almost 20%. CT scan abnormalities reflect the lymphocytic infiltrates and air trapping and, in some cases, the presence of emphysema. Bronchiolitis induced by chronic inhalation of mineral particles or acute inhalation of toxic gases (such as NO2) are other examples of small airways damage due to environmental exposure. The pathophysiological mechanisms are different and bronchiolar damage is either exclusive or predominant. Bronchiolitis induced by tobacco smoke exposure, usually classified as interstitial pneumonitis, is easily diagnosed thanks to broncho-alveolar lavage. Its prognosis is linked to the other consequences of tobacco smoke exposure including respiratory insufficiency. Finally, the complex lung exposure observed in some rare cases (such as the World Trade Center fire or during wars) may lead to a less characteristic pattern of small airways disease.

  17. Transepithelial water permeability in microperfused distal airways. Evidence for channel-mediated water transport.

    PubMed Central

    Folkesson, H G; Matthay, M A; Frigeri, A; Verkman, A S

    1996-01-01

    Water movement across the airway epithelium is important for regulation of the volume and composition of airspace fluid. A novel approach is reported here to measure osmotic and diffusional water permeability in intact airways. Small airways (100-200 microns diameter, 1-2 mm length) from guinea pig lung were microdissected and perfused in vitro using concentric glass holding and perfusion pipettes. For measurement of osmotic water permeability (Pf), the airway lumen was perfused wit PBS (300 mOsM) containing a membrane impermeable fluorophore, fluorescein sulfonate (FS), and the airway was bathed in solutions of specified osmolalities. Pf determination was based on the changes in FS fluorescence at the distal end of the airway resulting from transepithelial water transport. Pf was 4-5 x 10(-3) cm/s at 23 degrees C and independent of lumen flow rate (10-100 nl/min) and the magnitude and direction of the osmotic gradient (bath osmolality 50-600 mOsM). Temperature dependence measurements gave an activation energy of 4.4 kcal/mol (15-37 degrees C). Pf was not altered by 0.3 mM HgCl2 or 50 microM forskolin, but was increased to 31 x 10(-3) cm/s by 100 micrograms/ml amphotericin B, indicating that osmosis is not limited by unstirred layers. Diffusional water permeability (Pd) was measured by H2O/D2O (deuterium oxide) exchange using the H2O/D2O-sensitive fluorescent probe aminonapthelane trisulfonic acid in the lumen. Measured Pd was 3-6 x 10(-6) cm/s at 23 degrees C, indicating significant restriction to water diffusion by unstirred layers. Antibody localization of water channels showed strong expression of the mercurial-insensitive water channel (AQP-4) at the basolateral membrane of airway epithelial cells. These results provide functional evidence that water movement across the distal airway epithelium is mediated by water channels. PMID:8609221

  18. Transepithelial water permeability in microperfused distal airways. Evidence for channel-mediated water transport.

    PubMed

    Folkesson, H G; Matthay, M A; Frigeri, A; Verkman, A S

    1996-02-01

    Water movement across the airway epithelium is important for regulation of the volume and composition of airspace fluid. A novel approach is reported here to measure osmotic and diffusional water permeability in intact airways. Small airways (100-200 microns diameter, 1-2 mm length) from guinea pig lung were microdissected and perfused in vitro using concentric glass holding and perfusion pipettes. For measurement of osmotic water permeability (Pf), the airway lumen was perfused wit PBS (300 mOsM) containing a membrane impermeable fluorophore, fluorescein sulfonate (FS), and the airway was bathed in solutions of specified osmolalities. Pf determination was based on the changes in FS fluorescence at the distal end of the airway resulting from transepithelial water transport. Pf was 4-5 x 10(-3) cm/s at 23 degrees C and independent of lumen flow rate (10-100 nl/min) and the magnitude and direction of the osmotic gradient (bath osmolality 50-600 mOsM). Temperature dependence measurements gave an activation energy of 4.4 kcal/mol (15-37 degrees C). Pf was not altered by 0.3 mM HgCl2 or 50 microM forskolin, but was increased to 31 x 10(-3) cm/s by 100 micrograms/ml amphotericin B, indicating that osmosis is not limited by unstirred layers. Diffusional water permeability (Pd) was measured by H2O/D2O (deuterium oxide) exchange using the H2O/D2O-sensitive fluorescent probe aminonapthelane trisulfonic acid in the lumen. Measured Pd was 3-6 x 10(-6) cm/s at 23 degrees C, indicating significant restriction to water diffusion by unstirred layers. Antibody localization of water channels showed strong expression of the mercurial-insensitive water channel (AQP-4) at the basolateral membrane of airway epithelial cells. These results provide functional evidence that water movement across the distal airway epithelium is mediated by water channels.

  19. Clinical application of nasal nitric oxide measurement in pediatric airway diseases.

    PubMed

    Manna, Angelo; Montella, Silvia; Maniscalco, Mauro; Maglione, Marco; Santamaria, Francesca

    2015-01-01

    Nitric oxide plays an important role in several physiological and pathophysiological processes in the respiratory tract. Different ways to measure nasal nitric oxide levels in children are currently available. The possibility of obtaining nasal nitric oxide measurement from relatively young children, combined with the availability of portable devices that can be used even in the office setting, opens new perspectives for nasal nitric oxide analysis in the pediatric daily practice. This review presents a synopsis about the current clinical applications of nasal nitric oxide measurement in the pediatric clinical practice. A total of 3,775 articles on the topic were identified, of which 883 duplicates were removed, and 2,803 were excluded based on review of titles and abstracts. Eighty-nine full text articles were assessed for eligibility and 32 additional articles were obtained from the reference lists of the retrieved studies. Since very low nasal nitric oxide levels are found in the majority of patients with primary ciliary dyskinesia, most publications support a central role for nasal nitric oxide to screen the disease, and indicate that it is a very helpful first-line tool in the real-life work-up in all age groups. Decreased nasal nitric oxide concentration is also typical of cystic fibrosis, even though nasal nitric oxide is not as low as in primary ciliary dyskinesia. In other upper airway disorders such as allergic rhinitis, rhinosinusitis, nasal polyposis, and adenoidal hypertrophy, clinical utility of nasal nitric oxide is still critically questioned and remains to be established. Since nNO determination is flow dependent, a general consensus from the major investigators in this area is highly desirable so that future studies will be performed with the same flow rate. A shared nNO methodology will enable to overcome the challenges that lie ahead in incorporating nNO measurement into the mainstream clinical setting of pediatric airway diseases. © 2014 Wiley

  20. Effects of nitric acid on carbachol reactivity of the airways in normal and allergic sheep

    SciTech Connect

    Abraham, W.M.; Kim, C.S.; King, M.M.; Oliver, W. Jr.; Yerger, L.

    1982-01-01

    The airway effects of a 4-hr exposure (via a Plexiglas hood) to 1.6 ppm nitric acid vapor were evaluated in seven normal and seven allergic sheep, i.e., animals that have a history of reacting with bronchospasm to inhalation challenge with Ascaris suum antigen. The nitric acid vapor was generated by ultrasonic nebulization of a 2% nitric acid solution. Airway effects were assessed by measuring the change in specific pulmonary flow resistance before and after a standard inhalation challenge with 2.5% carbachol aerosol. Nitric acid exposure did not produce bronchoconstriction in either group. Pre-exposure increases in specific pulmonary flow resistance after carbachol inhalation were 68% (SD+/- 13%) and 82% (SD+/- 35%) for the normal and allergic sheep, respectively. Within 24 hr, the largest post-exposure increases in specific pulmonary flow resistance for the normal and allergic sheep were 108% (SD+/- 51%(P<.06)) and 175% (SD+/- 87% (p<.02)), respectively. We conclude that a short-term exposure to nitric acid vapor at levels below the industrial threshold limit (2 ppm), produces airway hyperreactivity to aerosolized carbachol in allergic sheep.

  1. Arginase inhibition in airways from normal and nitric oxide synthase 2-knockout mice exposed to ovalbumin

    SciTech Connect

    Bratt, Jennifer M.; Franzi, Lisa M.; Linderholm, Angela L.; O'Roark, Erin M.; Kenyon, Nicholas J.; Last, Jerold A.

    2010-01-01

    Arginase1 and nitric oxide synthase2 (NOS2) utilize L-arginine as a substrate, with both enzymes expressed at high levels in the asthmatic lung. Inhibition of arginase in ovalbumin-exposed C57BL/6 mice with the transition state inhibitor N{sup o}mega-hydroxy-nor-L-arginine (nor-NOHA) significantly increased total L-arginine content in the airway compartment. We hypothesized that such an increase in L-arginine content would increase the amount of nitric oxide (NO) being produced in the airways and thereby decrease airway hyperreactivity and eosinophilic influx. We further hypothesized that despite arginase inhibition, NOS2 knockout (NOS2-/-) mice would be unable to up-regulate NO production in response to allergen exposure and would demonstrate higher amounts of airway hyperreactivity and eosinophilia under conditions of arginase inhibition than C57BL/6 animals. We found that administration of nor-NOHA significantly decreased airway hyperreactivity and eosinophilic airway inflammation in ovalbumin-exposed C57BL/6 mice, but these parameters were unchanged in ovalbumin-exposed NOS2-/- mice. Arginase1 protein content was increased in mice exposed to ovalbumin, an effect that was reversed upon nor-NOHA treatment in C57BL/6 mice. Arginase1 protein content in the airway compartment directly correlated with the degree of airway hyperreactivity in all treatment groups. NOS2-/- mice had significantly greater arginase1 and arginase2 concentrations compared to their respective C57BL/6 groups, indicating that inhibition of arginase may be dependent upon NOS2 expression. Arginase1 and 2 content were not affected by nor-NOHA administration in the NOS2-/- mice. We conclude that L-arginine metabolism plays an important role in the development of airway hyperreactivity and eosinophilic airway inflammation. Inhibition of arginase early in the allergic inflammatory response decreases the severity of the chronic inflammatory phenotype. These effects appear to be attributable to NOS2

  2. Nasal nitric oxide improved by continuous positive airway pressure therapy for upper airway inflammation in obstructive sleep apnea.

    PubMed

    Hamada, Satoshi; Tatsumi, Shuji; Kobayashi, Yoshiki; Yasuba, Hirotaka

    2017-05-01

    In this report, we examined the association between obstructive sleep apnea (OSA) and upper and lower airway inflammation based on nitric oxide (NO) measurements. Study subjects included 51 consecutive participants. Sleep-disordered breathing was evaluated by a type 3 portable monitor and quantified by respiratory disturbance index (RDI). Airway inflammation was noninvasively analyzed by the measurement of nasally and orally exhaled NO; nasal value was presented as nasally exhaled NO minus orally exhaled NO. In 15 patients prescribed nasal continuous positive airway pressure (nCPAP) therapy, exhaled NO was re-evaluated in 10.7 ± 6.3 months after nCPAP therapy. Nasal NO was significantly higher in patients with severe OSA (RDI ≥ 30/h) than those with non-OSA (RDI < 10/h) (76.9 ± 26.0 ppb vs. 47.9 ± 22.0 ppb, respectively, p = 0.016) and correlated with RDI (rho = 0.36, p = 0.0099), whereas orally exhaled NO did not differ between non-OSA and OSA patients and was not correlated with RDI. In 15 patients, nasal NO after nCPAP therapy was significantly decreased than that before nCPAP therapy (81.9 ± 31.2 ppb vs. 53.7 ± 27.2 ppb, respectively, p = 0.0046); in 11 patients having good compliance to nCPAP therapy (nCPAP use >4 h per night on more than 70% of nights), this association was more remarkable. In OSA, upper but not lower airway inflammation can be increased by repetitive collapse of the upper airway. Future studies are required to determine the role of nasal NO in OSA.

  3. Bacterial colonization of distal airways in healthy subjects and chronic lung disease: a bronchoscopic study.

    PubMed

    Cabello, H; Torres, A; Celis, R; El-Ebiary, M; Puig de la Bellacasa, J; Xaubet, A; González, J; Agustí, C; Soler, N

    1997-05-01

    In contrast to the healthy population, distal airway bacterial colonization may occur in patients with chronic lung diseases, who often have altered pulmonary defences. However, the information dealing with this issue is insufficient and is based mainly on nonspecific samples, such as sputum cultures. Using quantitative cultures of bronchoscopic protected specimen brush (PSB) and bronchoalveolar lavage (BAL) samples, we studied the bacterial colonization of distal airways in 16 healthy subjects, 33 patients with bronchogenic carcinoma, 18 with chronic obstructive pulmonary disease (COPD), 17 with bronchiectasis, and 32 with a long-term tracheostomy due to laryngeal carcinoma. All patients were without exacerbation, and free from antibiotic treatment at least 1 month before the study protocol. Thresholds for quantitative cultures to define colonization were > or = 10(2) colony-forming units (cfu) x mL(-1) for PSB and > or = 10(3) cfu x mL(-1) for BAL. Only one healthy subject was colonized by a potential pathogenic microorganism (PPM) (Staphylococcus aureus 4x10(2) cfu x mL(-1) in a PSB culture). Colonization was observed in 14 (42%) bronchogenic carcinoma patients (19 non-PPMs, and 10 PPMs); in 15 (83%) COPD patients (22 non-PPMs and 7 PPMs); in 15 (88%) bronchiectasis patients (20 non-PPMs and 13 PPMs); and in 15 (47%) long-term tracheostomy patients (5 non-PPMs and 13 PPMs). The two most frequent non-PPMs isolated in all groups studied were Streptococcus viridans and Neisseria spp. Haemophilus spp., Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis were the most frequent PPMs isolated in bronchogenic carcinoma, COPD, bronchiectasis and long-term tracheostomized patients, respectively. Pseudomonas aeruginosa colonization was infrequent in all the groups. Our results show that distal airway bacterial colonization is a frequent feature in stable patients with chronic lung diseases and also in patients with long-term tracheostomy. However

  4. Reduced upper airway nitric oxide in cystic fibrosis.

    PubMed Central

    Balfour-Lynn, I M; Laverty, A; Dinwiddie, R

    1996-01-01

    Nitric oxide (NO) produced within the respiratory tract is detectable in exhaled and nasal air. Its synthesis may be induced by inflammatory cytokines and reduced by glucocorticoids. Increased concentrations have been found in asthma and bronchiectasis. In this study, NO concentrations were determined in 63 children with cystic fibrosis, of whom 13 were on inhaled steroids (mean age 13.3 years) and 50 were not (mean age 12.3 years); 57 normal children (mean age 12.2 years) were also studied. NO was measured by chemiluminescence analyser, exhaled NO following a relaxed vital capacity manoeuvre, and nasal NO with the breath held following a full inspiration. Mean concentration of exhaled NO in cystic fibrosis patients (no steroids) was 4.7 parts per billion (ppb) (95% confidence interval (CI) 4.0 to 5.3); this did not differ from values in normal children (mean 4.8 ppb, 95% CI 3.8 to 5.8) or in cystic fibrosis patients on inhaled steroids (mean 3.6 ppb, 95% CI 2.5 to 4.8). Nasal concentrations were significantly lower in cystic fibrosis patients, with or without inhaled steroids, than in normal children (cystic fibrosis, no inhaled steroids: 460 ppb, 95% CI 399 to 520; cystic fibrosis, inhaled steroids: 522 ppb, 95% CI 313 to 730, v normal children: 1024 ppb, 95% CI 896 to 1152, p < 0.0001). Considering the inflammatory nature of cystic fibrosis, it is surprising exhaled NO levels were not increased, but this may have been due to alteration in NO diffusion through thick mucus. The low nasal NO concentrations, which are probably the result of impaired flow from the paranasal sinuses, may contribute to the recurrent respiratory infections typical of cystic fibrosis. PMID:8984918

  5. Vest Chest Physiotherapy Airway Clearance is Associated with Nitric Oxide Metabolism.

    PubMed

    Sisson, Joseph H; Wyatt, Todd A; Pavlik, Jacqueline A; Sarna, Pawanjit S; Murphy, Peter J

    2013-01-01

    Background. Vest chest physiotherapy (VCPT) enhances airway clearance in cystic fibrosis (CF) by an unknown mechanism. Because cilia are sensitive to nitric oxide (NO), we hypothesized that VCPT enhances clearance by changing NO metabolism. Methods. Both normal subjects and stable CF subjects had pre- and post-VCPT airway clearance assessed using nasal saccharin transit time (NSTT) followed by a collection of exhaled breath condensate (EBC) analyzed for NO metabolites (NO x ). Results. VCPT shorted NSTT by 35% in normal and stable CF subjects with no difference observed between the groups. EBC NO x concentrations decreased 68% in control subjects after VCPT (before = 115 ± 32  μ M versus after = 37 ± 17  μ M; P < 0.002). CF subjects had a trend toward lower EBC NO x . Conclusion. We found an association between VCPT-stimulated clearance and exhaled NO x levels in human subjects. We speculate that VCPT stimulates clearance via increased NO metabolism.

  6. p63(+)Krt5(+) distal airway stem cells are essential for lung regeneration.

    PubMed

    Zuo, Wei; Zhang, Ting; Wu, Daniel Zheng'An; Guan, Shou Ping; Liew, Audrey-Ann; Yamamoto, Yusuke; Wang, Xia; Lim, Siew Joo; Vincent, Matthew; Lessard, Mark; Crum, Christopher P; Xian, Wa; McKeon, Frank

    2015-01-29

    Lung diseases such as chronic obstructive pulmonary disease and pulmonary fibrosis involve the progressive and inexorable destruction of oxygen exchange surfaces and airways, and have emerged as a leading cause of death worldwide. Mitigating therapies, aside from impractical organ transplantation, remain limited and the possibility of regenerative medicine has lacked empirical support. However, it is clinically known that patients who survive sudden, massive loss of lung tissue from necrotizing pneumonia or acute respiratory distress syndrome often recover full pulmonary function within six months. Correspondingly, we recently demonstrated lung regeneration in mice following H1N1 influenza virus infection, and linked distal airway stem cells expressing Trp63 (p63) and keratin 5, called DASC(p63/Krt5), to this process. Here we show that pre-existing, intrinsically committed DASC(p63/Krt5) undergo a proliferative expansion in response to influenza-induced lung damage, and assemble into nascent alveoli at sites of interstitial lung inflammation. We also show that the selective ablation of DASC(p63/Krt5) in vivo prevents this regeneration, leading to pre-fibrotic lesions and deficient oxygen exchange. Finally, we demonstrate that single DASC(p63/Krt5)-derived pedigrees differentiate to type I and type II pneumocytes as well as bronchiolar secretory cells following transplantation to infected lung and also minimize the structural consequences of endogenous stem cell loss on this process. The ability to propagate these cells in culture while maintaining their intrinsic lineage commitment suggests their potential in stem cell-based therapies for acute and chronic lung diseases.

  7. Diagnostic significance of nitric oxide concentrations in exhaled air from the airways in allergic rhinitis patients

    PubMed Central

    Krzych-Fałta, Edyta; Samoliński, Bolesław K; Zalewska, Marta

    2016-01-01

    Introduction The effect of nitric oxide (NO) on the human body is very important due its physiological regulation of the following functions of airways: modulation of ciliary movement and maintenance of sterility in sinuses. Aim To evaluate the diagnostic significance of NO concentrations in exhaled air from the upper and lower airways in patients diagnosed with allergic rhinitis (AR). Material and methods The subjects included in the study were a group of 30 people diagnosed with sensitivity to environmental allergens and a control group consisting of 30 healthy subjects. The measurement of NO in the air exhaled from the lower and upper airways was performed using an on-line method by means of Restricted Exhaled Breath (REB), as well as using the measurement procedure (chemiluminescence) set out in the guidelines prepared in 2005 by the American Thoracic Society and the European Respiratory Society. Results In the late phase of the allergic reaction, higher values of the level of exhaled NO concentration from the lower airways were observed in the groups of subjects up to the threshold values of 25.17 ppb in the group of subjects with year-round allergic rhinitis and 21.78 ppb in the group with diagnosed seasonal allergic rhinitis. The difference in the concentration of NO exhaled from the lungs between the test group and the control group in the 4th h of the test was statistically significant (p = 0.045). Conclusions Exhaled NO should be considered as a marker of airway inflammation. It plays an important role in the differential diagnosis of allergy. PMID:27279816

  8. Airway and alveolar nitric oxide measurements in obstructive sleep apnea syndrome.

    PubMed

    Fortuna, A M; Miralda, R; Calaf, N; González, M; Casan, P; Mayos, M

    2011-04-01

    The process of intermittent hypoxia-reoxygenation produces airway inflammation and endothelial dysfunction that favors the development of cardiovascular disorders in obstructive sleep apnea syndrome (OSAS). Nitric oxide (NO) is an important mediator in airway inflammation and the regulation of endothelium-dependent vasodilation. This study compared airway NO (FE(NO)) and alveolar NO (CA(NO)) measurements in exhaled breath in 30 OSAS patients to those of 30 healthy (non-OSAS) individuals and determined the relationship between NO levels and OSAS severity. Additionally, NO measurements were analyzed after 3 months of CPAP treatment. The mean (±SD) FE(NO) level in the OSAS group (27.2 ± 18 ppb) was higher than in the healthy non-OSAS group (p = 0.006). The mean CA(NO) level was 1.65 ± 0.90 ppb, lower than in the non-OSAS group (p = 0.001). A significant correlation was found between FE(NO) and CA(NO) levels and the apnea-hypopnea index (AHI) in the OSAS group (r = 0.8, p < 0.05; r = -0.9, p = 0.01, respectively). FE(NO) levels decreased and CA(NO) levels increased significantly after CPAP treatment. Severe OSAS patients have higher FE(NO) and lower CA(NO) levels and these are restored to normal after CPAP treatment, reflecting the correction of local upper airway inflammation and endothelial dysfunction present in OSAS patients. Exhaled breath techniques can be useful to identify airway inflammation and endothelial dysfunction in severe OSAS patients. Copyright © 2010 Elsevier Ltd. All rights reserved.

  9. Role of the nitric oxide-soluble guanylyl cyclase pathway in obstructive airway diseases.

    PubMed

    Dupont, Lisa L; Glynos, Constantinos; Bracke, Ken R; Brouckaert, Peter; Brusselle, Guy G

    2014-10-01

    Nitric oxide (NO) is a gaseotransmitter, which is involved in many signaling processes in health and disease. Three enzymes generate NO from l-arginine, with citrulline formed as a by-product: neuronal NO synthase (nNOS or NOS1), endothelial NOS (eNOS or NOS3) and inducible NOS (iNOS or NOS2). NO is a ligand of soluble guanylyl cyclase (sGC), an intracellular heterodimer enzyme that catalyzes the conversion of guanosine triphosphate (GTP) to cyclic GMP (cGMP). cGMP further activates protein kinase G that eventually reduces the smooth muscle tone in bronchi or vessels. Phosphodiesterase 5 (PDE5) degrades cGMP to GMP. However, NO reacts with superoxide anion (O2(-)), leading to formation of the pro-inflammatory molecule peroxynitrite. Under physiological conditions, NO plays a homeostatic bronchoprotective role in healthy subjects. In obstructive airway diseases, NO can be beneficial by its bronchodilating effect, but could also be detrimental by the formation of peroxynitrite. Since asthma and COPD are associated with increased levels of exhaled NO, chronic inflammation and increased airway smooth muscle tone, the NO/sGC/cGMP pathway could be involved in these highly prevalent obstructive airway diseases. Here we review the involvement of NO, NO synthases, guanylyl cyclases, cGMP and phophodiesterase-5 in asthma and COPD and potential therapeutic approaches to modulate this pathway. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Exhaled nitric oxide levels and airway responsiveness to adenosine 5'-monophosphate in subjects with nasal polyposis.

    PubMed

    Prieto, L; Seijas, T; Gutiérrez, V; Uixera, S; Bruno, L; López, R

    2004-08-01

    It is widely appreciated that asthma is an inflammatory disease of the airways associated with airway hyperresponsiveness, and that nasal polyposis and asthma are related diseases. The objective of this study was to determine differences in exhaled nitric oxide (ENO) levels and airway responsiveness to adenosine 5'-monophosphate (AMP) between nonasthmatic patients with nasal polyposis and healthy controls. Twenty patients without asthma with nasal polyposis and 16 healthy control subjects were enrolled in the study. Participants were challenged with increasing concentrations of AMP and methacholine. ENO was measured with the single-exhalation method. Bronchoconstriction in response to AMP was detected in 7 (35%) subjects with nasal polyposis. The geometric mean (95% CI) of ENO for subjects with nasal polyposis was 33.1 parts per billion (ppb) (24.0-45.7 ppb) compared with 12.3 ppb (8.5-18.2 ppb) for the healthy controls (p = 0.0002). ENO values were significantly higher in atopic than in nonatopic subjects with nasal polyposis [51.3 ppb (32.3-83.2 ppb) vs. 24.5 ppb (16.2-37.1 ppb), p = 0.02]. Nonatopic subjects with nasal polyposis also had higher concentrations of ENO than healthy control subjects (p = 0.016). Inhaled AMP causes airway narrowing in a significantly higher proportion of nonasthmatic subjects with nasal polyposis than in healthy controls. Furthermore, increased concentrations of ENO are detected in atopic and nonatopic subjects with nasal polyposis. These results suggest that bronchial inflammation is present in nonasthmatic subjects with nasal polyposis. Copyright 2004 S. Karger AG, Basel

  11. Staphylococcus aureus triggers nitric oxide production in human upper airway epithelium

    PubMed Central

    Carey, Ryan M.; Workman, Alan D.; Chen, Bei; Adappa, Nithin D.; Palmer, James N.; Kennedy, David W.; Lee, Robert J.; Cohen, Noam A.

    2016-01-01

    Background Nitric oxide (NO) is an important antibacterial defense molecule produced by upper airway (sinonasal) epithelial cells. We previously showed that a bitter taste receptor expressed in airway epithelium detects quorum-sensing molecules secreted by Gram-negative bacteria and subsequently triggers bactericidal NO production. We hypothesized that the upper airway epithelium may also be able to detect the Gram-positive aerobe Staphylococcus aureus and mount an NO response. Methods Human sinonasal air-liquid interface (ALI) cultures were treated with methicillin-resistant S. aureus (MRSA)-conditioned medium (CM), and NO production was measured using fluorescence imaging. Inhibitors of bitter taste receptor signaling were used to pharmacologically determine if this pathway was involved in the production of NO. Results A low-molecular-weight, heat, and protease-stabile product found in MRSA CM induced differential, NO synthase (NOS)-mediated NO production. This response varied markedly between individual patients. The MRSA-stimulated NO production was not dependent on 2 important components of bitter taste signaling: phospholipase C isoform β-2 or the transient receptor potential melastatin isoform 5 (TRPM5) ion channel. Conclusion This study shows that a S. aureus product elicits an NO-mediated innate defense response in human upper airway epithelium. The active bacterial product is likely a small, nonpeptide molecule that triggers a pathway independent of bitter taste receptors. Patient variation in the NO response to MRSA product(s), potentially due to genetic differences, might play a role in pathophysiology of Gram-positive upper respiratory infections and/or pathogenesis of chronic rhinosinusitis. PMID:26097237

  12. Nitric oxide induces airway smooth muscle cell relaxation by decreasing the frequency of agonist-induced Ca2+ oscillations

    PubMed Central

    Perez-Zoghbi, Jose F.; Bai, Yan

    2010-01-01

    Nitric oxide (NO) induces airway smooth muscle cell (SMC) relaxation, but the underlying mechanism is not well understood. Consequently, we investigated the effects of NO on airway SMC contraction, Ca2+ signaling, and Ca2+ sensitivity in mouse lung slices with phase-contrast and confocal microscopy. Airways that were contracted in response to the agonist 5-hydroxytryptamine (5-HT) transiently relaxed in response to the NO donor, NOC-5. This NO-induced relaxation was enhanced by zaprinast or vardenafil, two selective inhibitors of cGMP-specific phosphodiesterase-5, but blocked by ODQ, an inhibitor of soluble guanylyl cyclase, and by Rp-8-pCPT-cGMPS, an inhibitor of protein kinase G (PKG). Simultaneous measurements of airway caliber and SMC [Ca2+]i revealed that airway contraction induced by 5-HT correlated with the occurrence of Ca2+ oscillations in the airway SMCs. Airway relaxation induced by NOC-5 was accompanied by a decrease in the frequency of these Ca2+ oscillations. The cGMP analogues and selective PKG activators 8Br-cGMP and 8pCPT-cGMP also induced airway relaxation and decreased the frequency of the Ca2+ oscillations. NOC-5 inhibited the increase of [Ca2+]i and contraction induced by the photolytic release of inositol 1,4,5-trisphosphate (IP3) in airway SMCs. The effect of NO on the Ca2+ sensitivity of the airway SMCs was examined in lung slices permeabilized to Ca2+ by treatment with caffeine and ryanodine. Neither NOC-5 nor 8pCPT-cGMP induced relaxation in agonist-contracted Ca2+-permeabilized airways. Consequently, we conclude that NO, acting via the cGMP–PKG pathway, induced airway SMC relaxation by predominately inhibiting the release of Ca2+ via the IP3 receptor to decrease the frequency of agonist-induced Ca2+ oscillations. PMID:20176853

  13. Electrolyte transport properties in distal small airways from cystic fibrosis pigs with implications for host defense.

    PubMed

    Li, Xiaopeng; Tang, Xiao Xiao; Vargas Buonfiglio, Luis G; Comellas, Alejandro P; Thornell, Ian M; Ramachandran, Shyam; Karp, Philip H; Taft, Peter J; Sheets, Kelsey; Abou Alaiwa, Mahmoud H; Welsh, Michael J; Meyerholz, David K; Stoltz, David A; Zabner, Joseph

    2016-04-01

    While pathological and clinical data suggest that small airways are involved in early cystic fibrosis (CF) lung disease development, little is known about how the lack of cystic fibrosis transmembrane conductance regulator (CFTR) function contributes to disease pathogenesis in these small airways. Large and small airway epithelia are exposed to different airflow velocities, temperatures, humidity, and CO2 concentrations. The cellular composition of these two regions is different, and small airways lack submucosal glands. To better understand the ion transport properties and impacts of lack of CFTR function on host defense function in small airways, we adapted a novel protocol to isolate small airway epithelial cells from CF and non-CF pigs and established an organotypic culture model. Compared with non-CF large airways, non-CF small airway epithelia cultures had higher Cl(-) and bicarbonate (HCO3 (-)) short-circuit currents and higher airway surface liquid (ASL) pH under 5% CO2 conditions. CF small airway epithelia were characterized by minimal Cl(-) and HCO3 (-) transport and decreased ASL pH, and had impaired bacterial killing compared with non-CF small airways. In addition, CF small airway epithelia had a higher ASL viscosity than non-CF small airways. Thus, the activity of CFTR is higher in the small airways, where it plays a role in alkalinization of ASL, enhancement of antimicrobial activity, and lowering of mucus viscosity. These data provide insight to explain why the small airways are a susceptible site for the bacterial colonization. Copyright © 2016 the American Physiological Society.

  14. Electrolyte transport properties in distal small airways from cystic fibrosis pigs with implications for host defense

    PubMed Central

    Tang, Xiao Xiao; Vargas Buonfiglio, Luis G.; Comellas, Alejandro P.; Thornell, Ian M.; Ramachandran, Shyam; Karp, Philip H.; Taft, Peter J.; Sheets, Kelsey; Abou Alaiwa, Mahmoud H.; Welsh, Michael J.; Stoltz, David A.; Zabner, Joseph

    2016-01-01

    While pathological and clinical data suggest that small airways are involved in early cystic fibrosis (CF) lung disease development, little is known about how the lack of cystic fibrosis transmembrane conductance regulator (CFTR) function contributes to disease pathogenesis in these small airways. Large and small airway epithelia are exposed to different airflow velocities, temperatures, humidity, and CO2 concentrations. The cellular composition of these two regions is different, and small airways lack submucosal glands. To better understand the ion transport properties and impacts of lack of CFTR function on host defense function in small airways, we adapted a novel protocol to isolate small airway epithelial cells from CF and non-CF pigs and established an organotypic culture model. Compared with non-CF large airways, non-CF small airway epithelia cultures had higher Cl− and bicarbonate (HCO3−) short-circuit currents and higher airway surface liquid (ASL) pH under 5% CO2 conditions. CF small airway epithelia were characterized by minimal Cl− and HCO3− transport and decreased ASL pH, and had impaired bacterial killing compared with non-CF small airways. In addition, CF small airway epithelia had a higher ASL viscosity than non-CF small airways. Thus, the activity of CFTR is higher in the small airways, where it plays a role in alkalinization of ASL, enhancement of antimicrobial activity, and lowering of mucus viscosity. These data provide insight to explain why the small airways are a susceptible site for the bacterial colonization. PMID:26801568

  15. Generation of Distal Airway Epithelium from Multipotent Human Foregut Stem Cells.

    PubMed

    Hannan, Nicholas R F; Sampaziotis, Fotios; Segeritz, Charis-Patricia; Hanley, Neil A; Vallier, Ludovic

    2015-07-15

    Collectively, lung diseases are one of the largest causes of premature death worldwide and represent a major focus in the field of regenerative medicine. Despite significant progress, only few stem cell platforms are currently available for cell-based therapy, disease modeling, and drug screening in the context of pulmonary disorders. Human foregut stem cells (hFSCs) represent an advantageous progenitor cell type that can be used to amplify large quantities of cells for regenerative medicine applications and can be derived from any human pluripotent stem cell line. Here, we further demonstrate the application of hFSCs by generating a near homogeneous population of early pulmonary endoderm cells coexpressing NKX2.1 and FOXP2. These progenitors are then able to form cells that are representative of distal airway epithelium that express NKX2.1, GATA6, and cystic fibrosis transmembrane conductance regulator (CFTR) and secrete SFTPC. This culture system can be applied to hFSCs carrying the CFTR mutation Δf508, enabling the development of an in vitro model for cystic fibrosis. This platform is compatible with drug screening and functional validations of small molecules, which can reverse the phenotype associated with CFTR mutation. This is the first demonstration that multipotent endoderm stem cells can differentiate not only into both liver and pancreatic cells but also into lung endoderm. Furthermore, our study establishes a new approach for the generation of functional lung cells that can be used for disease modeling as well as for drug screening and the study of lung development.

  16. Effect of nitric oxide inhibition on nasal airway resistance after nasal allergen challenge in allergic rhinitis.

    PubMed

    Maniscalco, M; Sofia, M; Carratù, L; Higenbottam, T

    2001-05-01

    Nitric oxide has been detected by chemiluminescence in the lumen of nasal airway, which is increased in nasal breathing in patients with seasonal rhinitis during a chronic exposure. The purpose of this study was to determinate the effect of a NO-synthase inhibitor NGL-arginine methyl ester (L-NAME) on nasal airway resistance (NAR) in patients with seasonal allergic rhinitis after an acute challenge to the allergen. Nitric oxide levels in the nose were measured by the chemiluminescence method in nine non-atopic volunteers and in seven patients with seasonal rhinitis at rest and after an acute challenge with the allergen. NAR were measured by active anterior rhinomanometry. Basal nasal NO concentration in allergic rhinitis was 496.5 +/- 151.4 parts per billion (ppb). (n = 7) and it was not significantly different from levels found in the control group: 458.4 +/- 105.9 ppb (n = 9). The topical administration of L-NAME in allergic rhinitis reduced the NO concentration (338.6 +/- 99.3 ppb, P < 0.001; n = 7). In the rhinitic patients the challenge with the allergen did not modify the nasal NO levels (504.5 +/- 138.5 ppb). The application of the allergen after the pretreatment with placebo caused a significant increase in NAR (from 0.32 +/- 0.11 Pa s cm-3 to 1.01 +/- 0.12 Pa s cm-3, P < 0.001; n = 7). Pre-treatment with L-NAME did not prevent the increase in NAR induced by allergen challenge (from 0.36 +/- 0.15 Pa s cm-3 to 1.06 +/- 0.26 Pa s cm-3). The results indicate that nasal administration of a NOS inhibitor L-NAME, at doses capable of decreasing nasal NO levels, has no effect on NAR and it does not prevent the NAR increase induced by an acute challenge with allergen in subjects with seasonal rhinitis.

  17. Arginase enzymes in isolated airways from normal and nitric oxide synthase 2-knockout mice exposed to ovalbumin

    SciTech Connect

    Bratt, Jennifer M.; Franzi, Lisa M.; Linderholm, Angela L.; Last, Michael S.; Kenyon, Nicholas J. Last, Jerold A.

    2009-02-01

    Arginase has been suggested to compete with nitric oxide synthase (NOS) for their common substrate, L-arginine. To study the mechanisms underlying this interaction, we compared arginase expression in isolated airways and the consequences of inhibiting arginase activity in vivo with NO production, lung inflammation, and lung function in both C57BL/6 and NOS2 knockout mice undergoing ovalbumin-induced airway inflammation, a mouse model of asthma. Arginases I and II were measured by western blot in isolated airways from sensitized C57BL/6 mice exposed to ovalbumin aerosol. Physiological and biochemical responses - inflammation, lung compliance, airway hyperreactivity, exhaled NO concentration, arginine concentration - were compared with the responses of NOS2 knockout mice. NOS2 knockout mice had increased total cells in lung lavage, decreased lung compliance, and increased airway hyperreactivity. Both arginase I and arginase II were constitutively expressed in the airways of normal C57BL/6 mice. Arginase I was up-regulated approximately 8-fold in the airways of C57BL/6 mice exposed to ovalbumin. Expression of both arginase isoforms were significantly upregulated in NOS2 knockout mice exposed to ovalbumin, with about 40- and 4-fold increases in arginases I and II, respectively. Arginine concentration in isolated airways was not significantly different in any of the groups studied. Inhibition of arginase by systemic treatment of C57BL/6 mice with a competitive inhibitor, N{omega}-hydroxy-nor-L-arginine (nor-NOHA), significantly decreased the lung inflammatory response to ovalbumin in these animals. We conclude that NOS2 knockout mice are more sensitive to ovalbumin-induced airway inflammation and its sequelae than are C57BL/6 mice, as determined by increased total cells in lung lavage, decreased lung compliance, and increased airway hyperreactivity, and that these findings are strongly correlated with increased expression of both arginase isoforms in the airways of the

  18. Nitric Oxide and Airway Epithelial Barrier Function: Regulation of Tight Junction Proteins and Epithelial Permeability

    PubMed Central

    Olson, Nels; Greul, Anne-Katrin; Hristova, Milena; Bove, Peter F.; Kasahara, David I.; van der Vliet, Albert

    2008-01-01

    Acute airway inflammation is associated with enhanced production of nitric oxide (NO•) and altered airway epithelial barrier function, suggesting a role of NO• or its metabolites in epithelial permeability. While high concentrations of S-nitrosothiols disrupted transepithelial resistance (TER) and increased permeability in 16HBE14o- cells, no significant barrier disruption was observed by NONOates, in spite of altered distribution and expression of some TJ proteins. Barrier disruption of mouse tracheal epithelial (MTE) cell monolayers in response to inflammatory cytokines was independent of NOS2, based on similar effects in MTE cells from NOS2-/- mice and a lack of effect of the NOS2-inhibitor 1400W. Cell pre-incubation with LPS protected MTE cells from TER loss and increased permeability by H2O2, which was independent of NOS2. However, NOS2 was found to contribute to epithelial wound repair and TER recovery after mechanical injury. Overall, our results demonstrate that epithelial NOS2 is not responsible for epithelial barrier dysfunction during inflammation, but may contribute to restoration of epithelial integrity. PMID:19100237

  19. Pivotal role of c-Fos in nitric oxide synthase 2 expression in airway epithelial cells

    PubMed Central

    Chambellan, Arnaud; Leahy, Rachel; Xu, Weiling; Cruickshank, Paul J.; Janocha, Allison; Szabo, Katalin; Cannady, Steven B.; Comhair, Suzy A.A.; Erzurum, Serpil C.

    2010-01-01

    The regulation of nitric oxide synthase 2 (NOS2) in airway epithelial cells plays a key role in the innate host response to a wide variety of microbial agents and also participates in the generation of pathologic airway inflammation. Among the important signalling cascades that direct NOS2 gene expression are nuclear factor κB (NFκB) and interferon-γ (IFNγ)/signal transducer and activator of transcription 1 (STAT-1). Previous studies suggest activator protein-1 (AP-1), in particular c-Fos component of AP-1, influences NOS2 expression. We investigated the effect of c-Fos modulation using RNA interference siRNA on NOS2 gene expression. A549 cells stably transfected with a plasmid overexpressing a c-Fos siRNA construct (FOSi) resulted in a decrease of NOS2 protein inducibility by IFN γ. In contrast, classical IFN γ inducible signal transduction pathways interferon regulated factor-1 (IRF-1) and pSTAT-1 were activated at a similar magnitude in FOSi and control cells. DNA–protein binding assays showed that c-Fos binding was present in wild type cells, but reduced in FOSi clones. FOSi clones had activation of NFκB detectable by DNA–protein binding assays, which may have contributed to a decrease of NOS2 expression. Overall, these studies indicate that c-Fos is a requisite and specific component for inducible NOS2 expression. PMID:19135542

  20. Nitric oxide activation by distal redox modulation in tetranuclear iron nitrosyl complexes.

    PubMed

    de Ruiter, Graham; Thompson, Niklas B; Lionetti, Davide; Agapie, Theodor

    2015-11-11

    A series of tetranuclear iron complexes displaying a site-differentiated metal center was synthesized. Three of the metal centers are coordinated to our previously reported ligand, based on a 1,3,5-triarylbenzene motif with nitrogen and oxygen donors. The fourth (apical) iron center is coordinatively unsaturated and appended to the trinuclear core through three bridging pyrazolates and an interstitial μ4-oxide moiety. Electrochemical studies of complex [LFe3(PhPz)3OFe][OTf]2 revealed three reversible redox events assigned to the Fe(II)4/Fe(II)3Fe(III) (-1.733 V), Fe(II)3Fe(III)/Fe(II)2Fe(III)2 (-0.727 V), and Fe(II)2Fe(III)2/Fe(II)Fe(III)3 (0.018 V) redox couples. Combined Mössbauer and crystallographic studies indicate that the change in oxidation state is exclusively localized at the triiron core, without changing the oxidation state of the apical metal center. This phenomenon is assigned to differences in the coordination environment of the two metal sites and provides a strategy for storing electron and hole equivalents without affecting the oxidation state of the coordinatively unsaturated metal. The presence of a ligand-binding site allowed the effect of redox modulation on nitric oxide activation by an Fe(II) metal center to be studied. Treatment of the clusters with nitric oxide resulted in binding of NO to the apical iron center, generating a {FeNO}(7) moiety. As with the NO-free precursors, the three reversible redox events are localized at the iron centers distal from the NO ligand. Altering the redox state of the triiron core resulted in significant change in the NO stretching frequency, by as much as 100 cm(-1). The increased activation of NO is attributed to structural changes within the clusters, in particular, those related to the interaction of the metal centers with the interstitial atom. The differences in NO activation were further shown to lead to differential reactivity, with NO disproportionation and N2O formation performed by the more

  1. Nitric Oxide Activation by Distal Redox Modulation in Tetranuclear Iron Nitrosyl Complexes

    PubMed Central

    de Ruiter, Graham; Thompson, Niklas B.; Lionetti, Davide; Agapie, Theodor

    2016-01-01

    A series of tetranuclear iron complexes displaying a site-differentiated metal center were synthesized. Three of the metal centers are coordinated to our previously reported ligand, based on a 1,3,5-triarylbenzene motif with nitrogen and oxygen donors. The fourth (apical) iron center is coordinatively unsaturated and appended to the trinuclear core through three bridging pyrazolates and an interstitial μ4-oxide moiety. Electrochemical studies of complex [LFe3(PhPz)3OFe][OTf]2 revealed three reversible redox events assigned to the FeII4/FeII3FeIII (−1.733 V), FeII3FeIII/FeII2FeIII2 (−0.727 V), and FeII2FeIII2/FeIIFeIII3 (0.018 V) redox-couples. Complexes in all redox states were isolated, and three were characterized structurally by single crystal X-ray diffraction. Combined Mössbauer spectroscopic and crystallographic studies indicate that the change in oxidation state is exclusively localized at the triiron core, without changing the oxidation state of the apical metal center. This phenomenon is assigned to differences in the coordination environment of the two metal sites in the cluster, and provides a strategy for storing electron and hole equivalents without affecting the oxidation state of the coordinatively unsaturated metal. The presence of an additional single ligand-binding site allowed for study of the effect of redox modulation on nitric oxide activation by an FeII metal center. Treatment of the clusters with nitric oxide resulted in binding of NO to the apical iron center generating a {FeNO}7 moiety. As with the NO-free precursors, three reversible redox events are observed electrochemically and are localized at the iron centers distal from the NO ligand. Altering the redox state of the triiron core resulted in significant change in the NO stretching frequency, by as much as 100 cm−1, indicative of NO activation modulated by remote metal centers. The increased activation of NO is attributed to structural changes within the clusters, in

  2. Airway hyperresponsiveness to mannitol and methacholine and exhaled nitric oxide: a random-sample population study.

    PubMed

    Sverrild, Asger; Porsbjerg, Celeste; Thomsen, Simon Francis; Backer, Vibeke

    2010-11-01

    Studies of selected patient groups have shown that airway hyperresponsiveness (AHR) to mannitol is more specific than methacholine for the diagnosis of asthma, as well as more closely associated with markers of airway inflammation in asthma. We sought to compare AHR to mannitol and methacholine and exhaled nitric oxide (eNO) levels in a nonselected population sample. In 238 young adults randomly drawn from the nationwide civil registration list in Copenhagen, Denmark, AHR to mannitol and methacholine, as well as levels of eNO, were determined, and the association with asthma was analyzed. In diagnosing asthma the specificity of methacholine and mannitol was 80.2% (95% CI, 77.1% to 82.9%) and 98.4% (95% CI, 96.2% to 99.4%), respectively, with a positive predictive value of 48.6% versus 90.4%, whereas the sensitivity was 68.6% (95% CI, 57.1% to 78.4%) and 58.8% (95% CI, 50.7% to 62.6%), respectively. In asthmatic subjects AHR to mannitol was associated with increased eNO levels (positive AHR to mannitol: median, 47 ppb [interquartile range, 35-68 ppb]; negative AHR to mannitol: median, 19 ppb [interquartile range, 13-30 ppb]; P = .001), whereas this was not the case for AHR to methacholine (median of 37 ppb [interquartile range, 26-51 ppb] vs 24 ppb [interquartile range, 15-39 ppb], P = .13). In this random population sample, AHR to mannitol was less sensitive but more specific than methacholine in the diagnosis of asthma. Furthermore, AHR to mannitol was more closely associated with ongoing airway inflammation in terms of increased eNO levels. Copyright © 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  3. Oxidative Stress Regulates CFTR Gene Expression in Human Airway Epithelial Cells through a Distal Antioxidant Response Element

    PubMed Central

    Zhang, Zhaolin; Leir, Shih-Hsing

    2015-01-01

    Cystic fibrosis transmembrane conductance regulator gene (CFTR) expression in human airway epithelial cells involves the recruitment of distal cis-regulatory elements, which are associated with airway-selective DNase hypersensitive sites at −44 kb and −35 kb from the gene. The −35-kb site encompasses an enhancer that is regulated by the immune mediators interferon regulatory factor 1 and 2 and by nuclear factor Y. Here we investigate the −44-kb element, which also has enhancer activity in vitro in airway epithelial cells but is inactive in intestinal epithelial cells. This site contains an antioxidant response element (ARE) that plays a critical role in its function in airway cell lines and primary human bronchial epithelial cells. The natural antioxidant sulforaphane (SFN) induces nuclear translocation of nuclear factor, erythroid 2-like 2 (Nrf2), a transcription factor that regulates genes with AREs in their promoters, many of which are involved in response to injury. Under normal conditions, the −44-kb ARE is occupied by the repressor BTB and CNC homology 1, basic leucine zipper transcription factor (Bach1), and v-Maf avian musculoaponeurotic fibrosarcoma oncogene homolog K (MafK) heterodimers. After 2 hours of SFN treatment, Nrf2 displaces these repressive factors and activates CFTR expression. Site-directed mutagenesis shows that both the ARE and an adjacent NF-κB binding site are required for activation of the –44-kb element in airway epithelial cells. Moreover, this element is functionally linked to the −35-kb enhancer in modulating CFTR expression in response to environmental stresses in the airway. PMID:25259561

  4. Nitric oxide synthase enzymes in the airways of mice exposed to ovalbumin: NOS2 expression is NOS3 dependent.

    PubMed

    Bratt, Jennifer M; Williams, Keisha; Rabowsky, Michelle F; Last, Michael S; Franzi, Lisa M; Last, Jerold A; Kenyon, Nicholas J

    2010-01-01

    The function of the airway nitric oxide synthase (NOS) isoforms and the lung cell types responsible for its production are not fully understood. We hypothesized that NO homeostasis in the airway is important to control inflammation, which requires upregulation, of NOS2 protein expression by an NOS3-dependent mechanism. Mice from a C57BL/6 wild-type, NOS1(-/-), NOS2(-/-), and NOS3(-/-) genotypes were used. All mice strains were systemically sensitized and exposed to filtered air or ovalbumin (OVA) aerosol for two weeks to create a subchronic model of allergen-induced airway inflammation. We measured lung function, lung lavage inflammatory and airway epithelial goblet cell count, exhaled NO, nitrate and nitrite concentration, and airway NOS1, NOS2, and NOS3 protein content. Deletion of NOS1 or NOS3 increases NOS2 protein present in the airway epithelium and smooth muscle of air-exposed animals. Exposure to allergen significantly reduced the expression of NOS2 protein in the airway epithelium and smooth muscle of the NOS3(-/-) strain only. This reduction in NOS2 expression was not due to the replacement of epithelial cells with goblet cells as remaining epithelial cells did not express NOS2. NOS1(-/-) animals had significantly reduced goblet cell metaplasia compared to C57Bl/6 wt, NOS2(-/-), and NOS3(-/-) allergen-exposed mice. The airway epithelial and smooth muscle cells maintain a stable airway NO concentration under noninflammatory conditions. This "homeostatic" mechanism is unable to distinguish between NOS derived from the different constitutive NOS isoforms. NOS3 is essential for the expression of NOS2 under inflammatory conditions, while NOS1 expression contributes to allergen-induced goblet cell metaplasia.

  5. Nitric Oxide Synthase Enzymes in the Airways of Mice Exposed to Ovalbumin: NOS2 Expression Is NOS3 Dependent

    PubMed Central

    Bratt, Jennifer M.; Williams, Keisha; Rabowsky, Michelle F.; Last, Michael S.; Franzi, Lisa M.; Last, Jerold A.; Kenyon, Nicholas J.

    2010-01-01

    Objectives and Design. The function of the airway nitric oxide synthase (NOS) isoforms and the lung cell types responsible for its production are not fully understood. We hypothesized that NO homeostasis in the airway is important to control inflammation, which requires upregulation, of NOS2 protein expression by an NOS3-dependent mechanism. Materials or Subjects. Mice from a C57BL/6 wild-type, NOS1−/−, NOS2−/−, and NOS3−/− genotypes were used. All mice strains were systemically sensitized and exposed to filtered air or ovalbumin (OVA) aerosol for two weeks to create a subchronic model of allergen-induced airway inflammation. Methods. We measured lung function, lung lavage inflammatory and airway epithelial goblet cell count, exhaled NO, nitrate and nitrite concentration, and airway NOS1, NOS2, and NOS3 protein content. Results. Deletion of NOS1 or NOS3 increases NOS2 protein present in the airway epithelium and smooth muscle of air-exposed animals. Exposure to allergen significantly reduced the expression of NOS2 protein in the airway epithelium and smooth muscle of the NOS3−/− strain only. This reduction in NOS2 expression was not due to the replacement of epithelial cells with goblet cells as remaining epithelial cells did not express NOS2. NOS1−/− animals had significantly reduced goblet cell metaplasia compared to C57Bl/6 wt, NOS2−/−, and NOS3−/− allergen-exposed mice. Conclusion. The airway epithelial and smooth muscle cells maintain a stable airway NO concentration under noninflammatory conditions. This “homeostatic” mechanism is unable to distinguish between NOS derived from the different constitutive NOS isoforms. NOS3 is essential for the expression of NOS2 under inflammatory conditions, while NOS1 expression contributes to allergen-induced goblet cell metaplasia. PMID:20953358

  6. Increased nitric oxide concentrations in the small airway of older normal subjects.

    PubMed

    Gelb, Arthur F; George, Steven C; Camacho, Fernando; Fraser, Christine; Flynn Taylor, Colleen; Shakkottai, Sreelakshmi

    2011-02-01

    There is a paucity of normal-age stratified data for fraction of exhaled nitric oxide (Feno). Our goal was to obtain normal data for large-airway nitric oxide flux (J'awno) and small-airway and/or alveolar nitric oxide concentration (Cano) in nonsmoking, healthy, adult subjects of various ages. In 106 normal volunteer subjects (60 women) aged 55 ± 20 years (mean ± SD), Feno (parts per billion [ppb]) was measured at 50, 100, 150, and 200 mL/s and J'awno (nL/s) and Cano (ppb) were calculated using a two-compartment model with correction for axial nitric oxide (NO) back diffusion. Fourteen older normal subjects were also treated with inhaled corticosteroid (540 μg budesonide bid) for 14 days. We studied 34 younger normal subjects (17 women) aged 18 to 39 years (younger), 26 middle-aged normal subjects (22 women) aged 40 to 59 years (middle-aged), and 46 older normal subjects (21 women) aged 60 to 86 years (older). Feno at 50 mL/s in the younger group was 21 (14-28) ppb (median, 1-3 interquartile); in the middle-aged group it was 22 (18-30) ppb, and in the older group it was 27 (21-33) ppb, (analysis of variance [ANOVA]) P = .02. For Feno, the younger vs older groups was (Mann-Whitney) P = .03, and Feno in the combined younger and middle-aged groups was 21 (15-29) ppb vs 27 (21-33) ppb, P = .006 for the older group. Corrected J'awno in the younger group was 1.5 (1.0-2.1) nL/s; in the middle-aged group it was 1.4 (1.0-2.0) nL/s, and in the older group it was 1.8 (1.2-2.4) nL/s, (ANOVA) P = .3. Corrected Cano in the younger group was 1.9 (0.8-3.0) ppb; in the middle-aged group it was 2.8 (0.8-5.1) ppb, and in the older group it was 3.9 (1.4-6.6) ppb, (ANOVA) P = .02. Cano in the younger vs older groups was P = .003, and the combined younger and middle-aged group result was 2.0 (0.8-3.8) vs 3.9 (1.4-6.6), P = .01 in the older group. There was no change in NO gas exchange with inhaled corticosteroids. In nonsmoking healthy subjects with normal spirometry, Feno at 50 m

  7. Asymmetric dimethylarginine contributes to airway nitric oxide deficiency in patients with COPD.

    PubMed

    Aydin, Murat; Altintas, Nejat; Cem Mutlu, Levent; Bilir, Bulent; Oran, Mustafa; Tülübaş, Feti; Topçu, Birol; Tayfur, İsmail; Küçükyalçin, Volkan; Kaplan, Gizem; Gürel, Ahmet

    2017-05-01

    Asymmetric dimethylarginine (ADMA) and nitric oxide (NO) show their mechanism of action reciprocally, the balance between these molecules contributes to the tight regulation of airways tone and function. The aim of this study to determine the serum levels of ADMA and NO in patients with chronic obstructive pulmonary disease (COPD) and establish whether their level vary in relation to forced expiratory volume in 1s (FEV1 ), to assess their role in pathophysiology of COPD. This study consisted of 58 patients with COPD and 30 healthy subjects. Serum ADMA and NO levels were measured using enzyme-linked immunosorbent assay and the colorimetric method, respectively. Serum ADMA levels were significantly higher, however, NO levels were lower in patients with COPD compared with controls. ADMA levels were inversely correlated with NO levels. Serum ADMA and NO were significantly correlated with FEV1 . Multivariable logistic regression analysis revealed that serum ADMA and NO were independently and significantly associated with the presence of COPD. Multiple linear regression analysis showed that COPD was positively associated with ADMA, additionally COPD and ADMA were independently and inversely associated with NO. NO levels were decreased, ADMA levels were increased compliant with progression of COPD stages. While circulating ADMA is higher, NO is lower in COPD and both show a strong correlation to the degree of airflow limitation. ADMA seems to be a possible new marker of prognosis of COPD and can be a novel therapeutic target for the treatment of COPD. © 2015 John Wiley & Sons Ltd.

  8. [Imaging techniques in the examination of the distal airways: asthma and COPD].

    PubMed

    Franquet, Tomás

    2011-04-01

    Imaging techniques are highly useful diagnostic tools to study small airway diseases. Despite their differences, from a clinical pathological perspective, these diseases show similar radiological manifestations. High-resolution computed tomography (CT) is the technique of choice to study diffuse diseases and those of the small airways; the slices obtained in expiratory high-resolution CT scan should form part of the study protocol of small airway diseases. Based on the findings of high-resolution CT, small airway diseases can be divided into two large groups: (a) those presenting direct morphological signs of bronchiolar involvement, and (b) those showing indirect signs of bronchiolar involvement (air trapping/mosaic pattern). High-resolution CT is highly useful to study the complications of asthma (allergic bronchopulmonary aspergillosis) and to evaluate clinically similar processes, such as hypersensitivity pneumonitis. In asthmatic patients, multi-detector CT (MDTC) allows clinical symptoms, thickening of the airway wall and the degree of airflow obstruction to be directly correlated. MDTC is also useful for quantitative evaluation of the degree of air trapping in patients with emphysema. Magnetic resonance imaging after inhalation of distinct gases, such as (3)He and xenon-129 and dual-energy CT are also useful imaging techniques in the direct or indirect evaluation of the degree of airflow obstruction (air trapping).

  9. Sewing machine needle retrieval from distal airways using flexible bronchoscope under fluoroscopy.

    PubMed

    Mahmud, Talha; Shafiq, Adnan; Hafeez, Abdul; Saqib, Muhammad; Farooq, Sidrah

    2016-01-01

    18-year-old lady was admitted through emergency department after she accidently aspirated a long sewing machine needle into her airways. Upon examination, she was anxious with normal vital signs and without any respiratory distress with SpO2 of 98% on air. Systemic examination was normal except slightly reduced breath sounds intensity on right lower side of chest. Her chest radiograph revealed needle in right lower lobe but it was not visualized on bronchoscopic examination of airways up to sub segmental level. Using flexible bronchoscope under fluoroscope guidance, needle was retrieved successfully from posterior basal sub segment of right lower lobe utilizing alligator biopsy forceps, without any noticeable complication.

  10. Endotoxin-induced nitric oxide production rescues airway growth and maturation in atrophic fetal rat lung explants

    SciTech Connect

    Rae, C.; Cherry, J.I.; Land, F.M.; Land, S.C. . E-mail: s.c.land@dundee.ac.uk

    2006-10-13

    Inflammation induces premature maturation of the fetal lung but the signals causing this effect remain unclear. We determined if nitric oxide (NO) synthesis, evoked by Escherichia coli lipopolysaccharide (LPS, 2 {mu}g ml{sup -1}), participated in this process. Fetal rat lung airway surface complexity rose 2.5-fold over 96 h in response to LPS and was associated with increased iNOS protein expression and activity. iNOS inhibition by N6-(1-iminoethyl)-L-lysine-2HCl (L-NIL) abolished this and induced airway atrophy similar to untreated explants. Surfactant protein-C (SP-C) expression was also induced by LPS and abolished by L-NIL. As TGF{beta} suppresses iNOS activity, we determined if feedback regulation modulated NO-dependent maturation. LPS induced TGF{beta}1 release and SMAD4 nuclear translocation 96 h after treatment. Treatment of explants with a blocking antibody against TGF{beta}1 sustained NO production and airway morphogenesis whereas recombinant TGF{beta}1 antagonized these effects. Feedback regulation of NO synthesis by TGF{beta} may, thus, modulate airway branching and maturation of the fetal lung.

  11. Life-threatening upper airway edema caused by a distal rattlesnake bite.

    PubMed

    Hinze, J D; Barker, J A; Jones, T R; Winn, R E

    2001-07-01

    A 36-year-old man captured a timber rattlesnake and was accidentally envenomated in the thumb by the severed head. At a local emergency department, hypotension and confusion developed. Facial and glossal edema were also observed. Oxygen was delivered by face mask, and crystalloids and dopamine were administered. Respiratory distress developed with progressive hypoxemia. Intubation was unsuccessful because of massive glossal and epiglottic (laryngeal) edema, and an emergency cricothyrotomy was performed. High-dose antivenom therapy was administered, and mechanical ventilation was started. Recovery was rapid, and the patient was discharged from the hospital a week later. This is the first report of life-threatening upper airway edema caused by snake envenomation not in the vicinity of the head or neck.

  12. Measurement of nasal and fractional exhaled nitric oxide in children with upper airway inflammatory disease: Preliminary results.

    PubMed

    Liu, Dabo; Huang, Zhenyun; Huang, Yaping; Yi, Xinhua; Chen, Xi

    2015-12-01

    To assess the clinical significance of nasal nitric oxide (nNO) and fractional exhaled nitric oxide (FeNO) concentrations in children with upper airway inflammatory disease. Fifteen healthy children, 30 with allergic rhinitis (AR), 10 with non-allergic rhinitis (NAR), and 30 with sleep disordered breathing (SDB) were enrolled. The FeNO and nNO concentrations were measured non-invasively using a NIOX MINO system. Both nNO and FeNO were significantly higher in children with AR than in healthy children (P=0.000 and P=0.000, respectively). Compared to healthy children, nNO was also significant higher in children with NAR (P=0.011) or SDB (P=0.027). In contrast, FeNO did not differ from controls in children with NAR or SDB. Our data suggest that nNO has potential value for diagnosing upper airway inflammation. Moreover, elevated FeNO distinguishes allergic from non-allergic rhinitis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  13. The time course of ozone-induced neutrophilia in the proximal and distal airways of normal humans

    SciTech Connect

    Siefkin, A.D.; Schelegle, E.S.; McDonald, R.; Volz, W. )

    1990-02-26

    It has been demonstrated that the first aliquot used in sequential bronchoalveolar lavage (3 {times} 60 ml) washes more proximal conducting airways (PA), and that subsequent aliquots sample from more distal airways and alveolar surfaces. The authors studied the time course of ozone (O{sub 3}) induced neutrophilia in the PA and DAAS of 5 normal exercising (V{sub E} = 60 1 min{sup {minus}1}) human subjects exposed for 1 h to filtered air (FA) once and to 0.3 ppm ozone (O{sub 3}) on 3 separate days. Bronchoalveolar lavage fluid was obtained < 1 after FA and either < 1, 6, or 24 h after O{sub 3} exposure. FEV{sub 1.0} was measured before the exposures and lavages. Four 60 ml aliquots of 0.9% NaCl solution were sequentially instilled into and withdrawn from a subsegment of the right middle lobe. The first aliquot (PA sample) was analyzed separately from poled aliquots 2 thru 4 (DAAS sample). FEV{sub 1.0} was significantly decreased < 1 h following O{sub 3} exposure, but returned to pre-exposure values at 6 and 24 h after O{sub 3}. The percent of neutrophils in the PA sample were significantly elevated at 6 h (16.5%) and 24 h (9.2%) after O{sub 3}. The percent of neutrophils in the DAAS sample were significantly elevated at 6 h (4.1%) and 24 h (5.1%) after O{sub 3}. PA vs DAAS comparisons were not significant at < 1 h after FA or O{sub 3} (1.1% vs 1.1% and 3.7% vs. 1.8%, respectively), but were significant 6 h and 24 h after O{sub 3}. These data demonstrate O{sub 3} induced FEV{sub 1.0} decrements and airway neutrophilia follow different time courses and suggest that O{sub 3} induced neutrophilia is greater in the PA compared to the DAAS and that PA neutrophilia peaks and begins to recover sooner.

  14. Nitric oxide and vasoactive intestinal peptide as co-transmitters of airway smooth-muscle relaxation: analysis in neuronal nitric oxide synthase knockout mice.

    PubMed

    Hasaneen, Nadia A; Foda, Hussein D; Said, Sami I

    2003-09-01

    Both vasoactive intestinal peptide (VIP) and nitric oxide (NO) relax airway smooth muscle and are potential co-transmitters of neurogenic airway relaxation. The availability of neuronal NO synthase (nNOS) knockout mice (nNOS-/-) provides a unique opportunity for evaluating NO. To evaluate the relative importance of NO, especially that generated by nNOS, and VIP as transmitters of the inhibitory nonadrenergic, noncholinergic (NANC) system. In this study, we compared the neurogenic (tetrodotoxin-sensitive) NANC relaxation of tracheal segments from nNOS-/- mice and control wild-type mice (nNOS(+/+)), induced by electrical field stimulation (EFS). We also examined the tracheal contractile response to methacholine and its relaxant response to VIP. EFS (at 60 V for 2 ms, at 10, 15, or 20 Hz) dose-dependently reduced tracheal tension, and the relaxations were consistently smaller (approximately 40%) in trachea from nNOS-/- mice than from control wild-type mice (p < 0.001). VIP (10(- 8) to 10(-6) mol/L) induced concentration-dependent relaxations that were approximately 50% smaller in nNOS-/- tracheas than in control tracheas. Methacholine induced concentration-dependent contractions that were consistently higher in the nNOS-/- tracheas relative to wild-type mice tracheas (p > 0.05). Our data suggest that, in mouse trachea, NO is probably responsible for mediating a large (approximately 60%) component of neurogenic NANC relaxation, and a similar (approximately 50%) component of the relaxant effect of VIP. The results imply that NO contributes significantly to neurogenic relaxation of mouse airway smooth muscle, whether due to neurogenic stimulation or to the neuropeptide VIP.

  15. Exhaled nitric oxide from the central airway and alveoli in OSAHS patients: the potential correlations and clinical implications.

    PubMed

    Liu, Jie; Li, Zheng; Liu, Zilong; Zhu, Fen; Li, Wenjing; Jiang, Hong; Wu, Xiaodan; Song, Yuanlin; Li, Shanqun; Bai, Chunxue

    2016-03-01

    The aim of the study was to evaluate exhaled nitric oxide (eNO) derived from different areas of airway in obstructive sleep apnea hypopnea syndrome (OSAHS) patients with NO exchange model and investigate the potential application and interpretation of eNO in clinical setting. This study was divided into two parts. Firstly, we performed a case control study in 32 OSAHS patients and 27 non-OSAHS participants. Fractional eNO (FeNO) and eNO from the central airway (J'awNO) and from alveoli (CANO) were compared in OSAHS and control groups. Also, correlation of eNO to severity of OSAHS was analyzed. Secondly, a prospective study was conducted in 30 severe OSAHS patients who received a short-term nasal continuous positive airway pressure (nCPAP) treatment. We evaluated eNO, plasma ET-1 concentration, and echocardiography during the treatment process and explored the potential relationship among them. FeNO and J'awNO were higher in OSAHS and associated with disease severity, while CANO was relatively lower. After nCPAP treatment in severe OSAHS patients, FeNO and J'awNO decreased and CANO increased significantly. Substantial agreement was shown between the elevation of CANO and the decrease of plasma ET-1 concentration after nCPAP by Kappa analysis for consistency. Tei index, which is considered indicative of global right ventricular function, might be predicted by plasma ET-1 levels in severe OSAHS patients. NO exchange model provides us with more information of eNO derived from different areas. eNO is not only confirmed to be an effective method for airway inflammation evaluation in the follow-up of OSAHS, CANO may also serve as a useful marker in monitoring endothelial function, resistance of pulmonary circulation, and right ventricular function for clinical implication.

  16. Nitric oxide relaxes circular smooth muscle of rat distal colon through RhoA/Rho-kinase independent Ca2+ desensitisation

    PubMed Central

    Colpaert, Erwin E; Levent, Adnan; Lefebvre, Romain A

    2005-01-01

    The aim of this study in circular smooth muscle of rat distal colon was to determine whether Ca2+ desensitisation, in addition to mechanisms lowering cytosolic free Ca2+ concentration ([Ca2+]cyt), was involved in the relaxation elicited by nitric oxide (NO). Changes in isometric tension and [Ca2+]cyt were recorded simultaneously in fura-2-loaded strips. In methacholine (10−5 M)-precontracted preparations, exogenous NO (10−4 M), adenosine 5′-triphosphate (ATP; 10−3 M) and electrical field stimulation (EFS; 1 ms, 40 V, 4 Hz, 1 min) induced a decrease in smooth muscle tension, which was accompanied by a fall in [Ca2+]cyt. The sarcoplasmic/endoplasmic reticulum Ca2+ ATP-ase (SERCA) inhibitor thapsigargin (10−6 M) did not exert an influence on the decrease in tension produced by exogenous NO, but significantly attenuated the fall in [Ca2+]cyt. Both the relaxation and the fall in [Ca2+]cyt to ATP and EFS were unaffected by thapsigargin. Calyculin-A (10−6 M), a myosin light chain phosphatase (MLCP) inhibitor, significantly reduced the decrease in tension elicited by exogenous NO, but did not alter the fall in [Ca2+]cyt to exogenous NO. Inactivating RhoA by exoenzyme C3 (2 μg ml−1) or inhibiting Rho-kinase with (+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl) cyclohexanecarboxamide dihydrochloride monohydrate (Y-27632; 10−5 M) had no effect on the decrease of both tension and [Ca2+]cyt generated by exogenous NO. This paper demonstrates that a RhoA/Rho-kinase independent Ca2+ desensitisation pathway contributes to the relaxation by NO in circular smooth muscle strips of rat distal colon. PMID:15655498

  17. Alcohol stimulates ciliary motility of isolated airway axonemes through a nitric oxide, cyclase, and cyclic nucleotide-dependent kinase mechanism.

    PubMed

    Sisson, Joseph H; Pavlik, Jacqueline A; Wyatt, Todd A

    2009-04-01

    Lung mucociliary clearance provides the first line of defense from lung infections and is impaired in individuals who consume heavy amounts of alcohol. Previous studies have demonstrated that this alcohol-induced ciliary dysfunction occurs through impairment of nitric oxide (NO) and cyclic nucleotide-dependent kinase-signaling pathways in lung airway ciliated epithelial cells. Recent studies have established that all key elements of this alcohol-driven signaling pathway co-localize to the apical surface of the ciliated cells with the basal bodies. These findings led us to hypothesize that alcohol activates the cilia stimulation pathway at the organelle level. To test this hypothesis we performed experiments exposing isolated demembranated cilia (isolated axonemes) to alcohol and studied the effect of alcohol-stimulated ciliary motility on the pathways involved with isolated axoneme activation. Isolated demembranated cilia were prepared from bovine trachea and activated with adenosine triphosphate. Ciliary beat frequency, NO production, adenylyl and guanylyl cyclase activities, cAMP- and cGMP-dependent kinase activities were measured following exposure to biologically relevant concentrations of alcohol. Alcohol rapidly stimulated axoneme beating 40% above baseline at very low concentrations of alcohol (1 to 10 mM). This activation was specific to ethanol, required the synthesis of NO, the activation of soluble adenylyl cyclase (sAC), and the activation of both cAMP- and cGMP-dependent kinases (PKA and PKG), all of which were present in the isolated organelle preparation. Alcohol rapidly and sequentially activates the eNOS-->NO-->GC-->cGMP-->PKG and sAC-->cAMP--> PKA dual signaling pathways in isolated airway axonemes. These findings indicate a direct effect of alcohol on airway cilia organelle function and fully recapitulate the alcohol-driven activation of cilia known to exist in vivo and in intact lung ciliated cells in vitro following brief moderate alcohol

  18. Increased levels of alveolar and airway exhaled nitric oxide in runners.

    PubMed

    Thornadtsson, Alexandra; Drca, Nikola; Ricciardolo, Fabio; Högman, Marieann

    2017-06-01

    The objective of this study was to apply extended NO analysis for measurements of NO dynamics in the lung, divided into alveolar and airway contribution, in amateur runners and marathoners. The athletes participated in either a marathon or a half marathon. The athletes self-reported their age, weight, height, training distance per week, competing distance, cardio-pulmonary health, atopic status, and use of tobacco. Measurements of exhaled NO (FENO) with estimation of alveolar NO (CANO) and airway flux (JawNO), ventilation, pulse oximetry, and peak flow were performed before, immediately after, and 1 hour after completing the race. At baseline the alveolar NO was higher in amateur runners, 2.9 ± 1.1 ppb (p = 0.041), and marathoners, 3.6 ± 1.9 ppb (p = 0.002), than in control subjects, 1.4 ± 0.5 ppb. JawNO was higher in marathoners, 0.90 ± 0.02 nL s(-1) (p = 0.044), compared with controls, 0.36 ± 0.02 nL s(-1), whereas the increase in amateur runners, 0.56 ± 0.02 nL s(-1), did not attain statistical significance (p = 0.165). Immediately after the race there was a decrease in FENO in both amateur runners and marathoners, whereas CANO and JawNO were decreased in marathoners only. Our results support the view that there is an adaptation of the lung to exercise. Thus strenuous exercise increased both airway and alveolar NO, and this might in turn facilitate oxygen uptake.

  19. [Exhaled nitric oxide in children: a noninvasive marker of airway inflammation].

    PubMed

    Cobos Barroso, Nicolás; Pérez-Yarza, Eduardo G; Sardón Prado, Olaia; Reverté Bover, Conrado; Gartner, Silvia; Korta Murua, Javier

    2008-01-01

    This article is an academic review of the application in children of the measurement of fractional exhaled nitric oxide (FENO). We outline the joint American Thoracic Society/European Respiratory Society recommendations for online measurement of FENO in both cooperating children and children unable to cooperate, offline measurement with uncontrolled exhalation flow rate, offline measurement with controlled exhalation flow rate using a dynamic flow restrictor, and offline measurement during tidal breathing in children unable to cooperate. This is followed by a review of the normal range of values for single-breath online measurements obtained with a chemiluminescence FENO analyzer (geometric mean, 9.7 parts per billion [ppb]; upper limit of the 95% confidence interval, 25.2 ppb). FENO values above 17 ppb have a sensitivity of 81% and a specificity of 80% for predicting asthma of an eosinophilic phenotype. We discuss the response of FENO values to anti-inflammatory treatment and the use of this marker in the management of asthma. Results obtained with chemiluminescence and portable electrochemical analyzers are compared. The portable devices offer the possibility--in children over 5 years of age--of accurate and universal monitoring of exhaled nitric oxide concentrations, an emerging marker of eosinophilic inflammation in asthma that facilitates diagnosis, monitoring of disease progression, and assessment of response to therapy.

  20. The effect of caffeinated coffee on airway response to methacholine and exhaled nitric oxide.

    PubMed

    Yurach, Madison T; Davis, Beth E; Cockcroft, Donald W

    2011-11-01

    The bronchoprotective effect of caffeine on histamine challenge testing (HCT) has been studied with equivocal results. Current guidelines for bronchoprovocation testing recommend exclusion of caffeine the day of testing. The effects of caffeine on methacholine challenge testing (MCT), now more commonly performed than histamine challenge, are unknown. Sixteen well-controlled asthmatics with a forced expiratory volume in 1 s (FEV(1)) > 65% predicted and methacholine provocation concentration causing a 20% fall in FEV(1) (PC(20)) ≤ 16 mg/ml participated in a randomized single-blind crossover study. The two treatments included 16 ounces of caffeinated and decaffeinated coffee given on two separate days. The fraction of exhaled nitric oxide (eNO) and FEV(1) were measured before and 1 h after each treatment. One hour post treatment blood was drawn for serum caffeine level and the MCT was done. Fourteen subjects completed the study; there were no adverse events. No significant bronchodilation was seen between the mean FEV(1) values before and after the caffeinated treatment (3.31 ± 0.75 L and 3.36 ± 0.74 L, respectively). No significant bronchoprotection was seen between the caffeinated and decaffeinated treatment's geometric mean PC(20) values (1.35 mg/ml and 1.36 mg/ml, respectively). Mean eNO values before and after caffeinated treatment were not significantly different (31.2 ± 19.6 ppb and 31.5 ± 20.4 ppb). The amount of caffeine in a normal dietary serving of a 16 oz cup of coffee is not enough to cause significant bronchoprotection, bronchodilation, or decrease eNO values. Registered at http://clinicaltrials.gov: NCT01057875. Copyright © 2011 Elsevier Ltd. All rights reserved.

  1. Nitric oxide in chronic airway inflammation in children: diagnostic use and pathophysiological significance

    PubMed Central

    Narang, I; Ersu, R; Wilson, N; Bush, A

    2002-01-01

    Background: The levels of exhaled and nasal nitric oxide (eNO and nNO) in groups of patients with inflammatory lung diseases are well documented but the diagnostic use of these measurements in an individual is unknown. Methods: The levels of nNO and eNO were compared in 31 children with primary ciliary dyskinesia (PCD), 21 with non-CF bronchiectasis (Bx), 17 with cystic fibrosis (CF), 35 with asthma (A), and 53 healthy controls (C) using a chemiluminescence NO analyser. A diagnostic receiver-operator characteristic (ROC) curve for PCD using NO was constructed. Results: The median (range) levels of nNO in parts per billion (ppb) in PCD, Bx, CF, and C were 60.3 (3.3–920), 533.6 (80–2053), 491.3 (31–1140), and 716 (398–1437), respectively; nNO levels were significantly lower in PCD than in all other groups (p<0.05). The median (range) levels of eNO in ppb in PCD, Bx, CF, A, and C were 2.0 (0.2–5.2), 5.4 (1.0–22.1), 2.6 (0.8–12.9), 10.7 (1.6–46.7), and 4.85 (2.5–18.3), respectively. The difference in eNO levels in PCD reached significance (p<0.05) when compared with those in Bx, A and C but not when compared with CF. Using the ROC curve, nNO of 250 ppb showed a sensitivity of 97% and a specificity of 90% for the diagnosis of PCD. Conclusions: eNO and nNO cannot be used diagnostically to distinguish between most respiratory diseases. However, nNO in particular is a quick and useful diagnostic marker which may be used to screen patients with a clinical suspicion of PCD. PMID:12096200

  2. Airway function, oedema, cell infiltration and nitric oxide generation in conscious ozone-exposed guinea-pigs: effects of dexamethasone and rolipram.

    PubMed

    Toward, Toby J; Broadley, Kenneth J

    2002-07-01

    1. The effects of ozone inhalation (90 min, 2.15+/-0.05 p.p.m.) and their modification by dexamethasone (20 mg kg(-1)) or the phosphodiesterase-4 inhibitor, rolipram (1 mg kg(-1)), administered (i.p.) 24 and 0.5 h before and 24 h after ozone exposure were examined in conscious guinea-pigs. 2. Ozone caused an early-phase bronchoconstriction (EPB) as a fall in specific airways conductance (sG(aw)) measured by whole body plethysmography, followed at 5 h by a late-phase bronchoconstriction (LPB) and increased respiratory rate. Rolipram did not alter this profile but dexamethasone inhibited the EPB. 3. Airway hyperreactivity to inhaled histamine (1 mM, 20 s) occurred at 0.5, 2, 12, 24 and 48 h after ozone inhalation, the 2 h change being abolished by rolipram and dexamethasone. 4. Bronchoalveolar lavage fluid (BALF) macrophages, eosinophils and neutrophils were significantly (P<0.05) elevated at 12, 24 and 48 h after ozone exposure, the 48 h influx being significantly attenuated (P<0.05) by rolipram and dexamethasone. 5. BALF nitric oxide (NO) metabolites decreased 0.5 h after ozone exposure by 52%, recovered at 2 h and significantly increased at 12 (101%) and 24 h (127%). The elevated NO was unaffected by rolipram or dexamethasone. 6. Lung oedema, measured from wet/dry weight differences, was significant 12, 24 and 48 h after ozone exposure, the latter being significantly attenuated (P<0.05) by rolipram and dexamethasone. 7. Ozone exposure of guinea-pigs produced features common to COPD. Although rolipram and dexamethasone did not affect the airway function changes, they inhibited the inflammation, airway hyperreactivity and oedema.

  3. Biomarkers of World Trade Center Particulate Matter Exposure: Physiology of distal airway and blood biomarkers that predict FEV1 decline

    PubMed Central

    Weiden, Michael D.; Kwon, Sophia; Caraher, Erin; Berger, Kenneth I.; Reibman, Joan; Rom, William N.; Prezant, David J.; Nolan, Anna

    2016-01-01

    Biomarkers can be important predictors of disease severity and progression. The intense exposure to particulates and other toxins from the destruction of the World Trade Center (WTC) overwhelmed the lung’s normal protective barriers. The Fire Department of New York (FDNY) cohort not only had baseline pre-exposure lung function measures but also had serum samples banked soon after their WTC exposure. This well phenotyped group of highly exposed first responders is an ideal cohort for biomarker discovery and eventual validation. Disease progression was heterogeneous in this group in that some individuals subsequently developed abnormal lung function while others recovered. Airflow obstruction predominated in WTC exposed patients who were symptomatic. Multiple independent disease pathways may cause this abnormal FEV1 after irritant exposure. WTC exposure activates one or more of these pathways causing abnormal FEV1 in an individual. Our hypothesis was that serum biomarkers expressed within 6 months after World Trade Center (WTC) exposure reflect active disease pathways and predict subsequent development or protection from abnormal FEV1airway injury after particulate exposures can focus monitoring and early treatment on a subset of patients in greatest need of these services. PMID:26024341

  4. Biomarkers of World Trade Center Particulate Matter Exposure: Physiology of Distal Airway and Blood Biomarkers that Predict FEV₁ Decline.

    PubMed

    Weiden, Michael D; Kwon, Sophia; Caraher, Erin; Berger, Kenneth I; Reibman, Joan; Rom, William N; Prezant, David J; Nolan, Anna

    2015-06-01

    Biomarkers can be important predictors of disease severity and progression. The intense exposure to particulates and other toxins from the destruction of the World Trade Center (WTC) overwhelmed the lung's normal protective barriers. The Fire Department of New York (FDNY) cohort not only had baseline pre-exposure lung function measures but also had serum samples banked soon after their WTC exposure. This well-phenotyped group of highly exposed first responders is an ideal cohort for biomarker discovery and eventual validation. Disease progression was heterogeneous in this group in that some individuals subsequently developed abnormal lung function while others recovered. Airflow obstruction predominated in WTC-exposed patients who were symptomatic. Multiple independent disease pathways may cause this abnormal FEV1 after irritant exposure. WTC exposure activates one or more of these pathways causing abnormal FEV1 in an individual. Our hypothesis was that serum biomarkers expressed within 6 months after WTC exposure reflect active disease pathways and predict subsequent development or protection from abnormal FEV1 below the lower limit of normal known as WTC-Lung Injury (WTC-LI). We utilized a nested case-cohort control design of previously healthy never smokers who sought subspecialty pulmonary evaluation to explore predictive biomarkers of WTC-LI. We have identified biomarkers of inflammation, metabolic derangement, protease/antiprotease balance, and vascular injury expressed in serum within 6 months of WTC exposure that were predictive of their FEV1 up to 7 years after their WTC exposure. Predicting future risk of airway injury after particulate exposures can focus monitoring and early treatment on a subset of patients in greatest need of these services. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  5. Contribution of exhaled nitric oxide measurement in airway inflammation assessment in asthma. A position paper from the French Speaking Respiratory Society.

    PubMed

    Dinh-Xuan, A T; Annesi-Maesano, I; Berger, P; Chambellan, A; Chanez, P; Chinet, T; Degano, B; Delclaux, C; Demange, V; Didier, A; Garcia, G; Magnan, A; Mahut, B; Roche, N

    2015-02-01

    Nitric oxide (NO) is both a gas and a ubiquitous inter- and intracellular messenger with numerous physiological functions. As its synthesis is markedly increased during inflammatory processes, NO can be used as a surrogate marker of acute and/or chronic inflammation. It is possible to quantify fractional concentration of NO in exhaled breath (FENO) to detect airway inflammation, and thus improve the diagnosis of asthma by better characterizing asthmatic patients with eosinophilic bronchial inflammation, and eventually improve the management of targeted asthmatic patients. FENO measurement can therefore be viewed as a new, reproducible and easy to perform pulmonary function test. Measuring FENO is the only non-invasive pulmonary function test allowing (1) detecting, (2) quantifying and (3) monitoring changes in inflammatory processes during the course of various respiratory disorders, including corticosensitive asthma. Copyright © 2014 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  6. Interferon gamma and interleukin 4 stimulate prolonged expression of inducible nitric oxide synthase in human airway epithelium through synthesis of soluble mediators.

    PubMed Central

    Guo, F H; Uetani, K; Haque, S J; Williams, B R; Dweik, R A; Thunnissen, F B; Calhoun, W; Erzurum, S C

    1997-01-01

    Human respiratory epithelium expresses inducible nitric oxide synthase (iNOS) continuously in vivo, however mechanisms responsible for maintenance of expression are not known. We show that IFNgamma is sufficient for induction of iNOS in primary human airway epithelial cells (HAEC) in vitro, and IL-4 potentiates IFNgamma-induced iNOS expression in HAEC through stabilization of iNOS mRNA. IFNgamma/IL-4- induced iNOS expression in HAEC was delayed in onset and prolonged with expression up to 1 wk. Removal of overlying culture media resulted in loss of expression, while transfer of conditioned media induced iNOS mRNA in other HAEC. IFNgamma and IL-4 stimulation activated STAT1 and STAT6 in HAEC, but conditioned media transfer to HAEC produced even higher levels of STAT1 activation than achieved by direct addition of cytokines. Although cytokine induction of iNOS was dependent on new protein synthesis, conditioned media induction of iNOS in HAEC was not. Further, removal of overlying culture media from cells at different times after cytokine stimulation demonstrated that mediator synthesis and/or secretion important for induction and maintenance of iNOS occurs early after cytokine stimulation. In conclusion, a combination of IFNgamma/ IL-4, which occurs naturally in the lung epithelial lining fluid, leads to maintenance of iNOS expression in human airway epithelium through production of soluble mediators and stabilization of mRNA. PMID:9259582

  7. A pilot study of inhaled nitric oxide in preterm infants treated with nasal continuous positive airway pressure for respiratory distress syndrome.

    PubMed

    Lindwall, Robert; Blennow, Mats; Svensson, Mats; Jonsson, Baldvin; Berggren-Boström, Eva; Flanby, Martino; Lönnqvist, Per-Arne; Frostell, Claes; Norman, Mikael

    2005-07-01

    To explore the acute effects of inhaled nitric oxide (iNO) on oxygenation, respiratory rate, and CO2 levels in spontaneously breathing preterm infants treated with nasal continuous positive airway pressure (nCPAP) for moderate respiratory distress syndrome (RDS). Randomized, prospective, double-blind, cross-over study in the neonatal intensive care units of a university hospital. 15 infants treated for RDS, with a median gestational age of 32 weeks (27-36), birth weight 1940 g (1100-4125), and postnatal age at the beginning of study 23 h (3-91). nCPAP pressure was kept constant at 4.3 cmH2O (3.4-5.1). We examined effects on gas exchange and vital signs during a 30-min exposure to 10 ppm iNO or placebo gas (nitrogen). Before administering test gases the baseline arterial to alveolar oxygen tension ratio (aAPO2) was 0.19+/-0.06. aAPO2 remained unchanged during placebo but increased to 0.22+/-0.05 (+20%) during iNO exposure. Respiratory rate and arterial carbon dioxide tension remained unchanged, as did heart rate, blood pressure, and methemoglobin. Follow-up at 30 days of age showed no deaths, delayed morbidity, or need for supplemental oxygen. Adding 10 ppm nitric oxide to nasal CPAP treatment in preterm infants suffering from RDS results in a moderate but statistically significant improvement in oxygenation, with no effect on respiratory drive or systemic circulatory parameters.

  8. Potential of Inducible Nitric Oxide Synthase as a Therapeutic Target for Allergen-Induced Airway Hyperresponsiveness: A Critical Connection to Nitric Oxide Levels and PARP Activity

    PubMed Central

    Ghonim, Mohamed A.; Pyakurel, Kusma; Mishra, Anil

    2016-01-01

    Although expression of inducible NO synthase (iNOS) in the lungs of asthmatics and associated nitrosative damage are established, iNOS failed as a therapeutic target for blocking airway hyperresponsiveness (AHR) and inflammation in asthmatics. This dichotomy calls for better strategies with which the enzyme is adequately targeted. Here, we confirm iNOS expression in the asthmatic lung with concomitant protein nitration and poly(ADP-ribose) polymerase (PARP) activation. We show, for the first time, that iNOS is highly expressed in peripheral blood mononuclear cells (PBMCs) of asthmatics with uncontrolled disease, which did not correspond to protein nitration. Selective iNOS inhibition with L-NIL protected against AHR upon acute, but not chronic, exposure to ovalbumin or house dust mite (HDM) in mice. Supplementation of NO by nitrite administration significantly blocked AHR in chronically HDM-exposed mice that were treated with L-NIL. Protection against chronic HDM exposure-induced AHR by olaparib-mediated PARP inhibition may be associated with the partial but not the complete blockade of iNOS expression. Indeed, L-NIL administration prevented olaparib-mediated protection against AHR in chronically HDM-exposed mice. Our study suggests that the amount of iNOS and NO are critical determinants in the modulation of AHR by selective iNOS inhibitors and renews the potential of iNOS as a therapeutic target for asthma. PMID:27524861

  9. Elective use of veno-venous extracorporeal membrane oxygenation and high-flow nasal oxygen for resection of subtotal malignant distal airway obstruction.

    PubMed

    Fung, Rkf; Stellios, J; Bannon, P G; Ananda, A; Forrest, P

    2017-01-01

    We describe the use of peripheral veno-venous extracorporeal membrane oxygenation (VV ECMO) and high-flow nasal oxygen as procedural support in a patient undergoing debulking of a malignant tumour of the lower airway. Due to the significant risk of complete airway obstruction upon induction of anaesthesia, ECMO was established while the patient was awake, and was maintained without systemic anticoagulation to minimise the risk of intraoperative bleeding. This case illustrates that ECMO support with high-flow nasal oxygen can be considered as part of the algorithm for airway management during surgery for subtotal lower airway obstruction, as it may be the only viable option for maintaining adequate gas exchange.

  10. Amelioration of vascular endothelial dysfunction in obstructive sleep apnea syndrome by nasal continuous positive airway pressure--possible involvement of nitric oxide and asymmetric NG, NG-dimethylarginine.

    PubMed

    Ohike, Yumiko; Kozaki, Koichi; Iijima, Katsuya; Eto, Masato; Kojima, Taro; Ohga, Eijiro; Santa, Tomofumi; Imai, Kazuhiro; Hashimoto, Masayoshi; Yoshizumi, Masao; Ouchi, Yasuyoshi

    2005-02-01

    Asymmetric NG,NG-dimethylarginine (ADMA) is an endogenous inhibitor of endothelial nitric oxide (NO) synthase and its plasma concentration is elevated in patients with cardiovascular risk factors, including hyperlipidemia, hypertension, diabetes, and hyperhomocysteinemia. Obstructive sleep apnea syndrome (OSAS) has been attracting attention as a risk factor for cardiovascular disorders because it often accompanies hypertension, obesity, glucose impairment, and dyslipidemia, all of which are factors in metabolic syndrome and risk factors for cardiovascular disease. In the present study, flow-mediated vasodilatation (FMD) of the brachial artery and plasma concentrations of ADMA were measured before and after nasal continuous positive airway pressure (nCPAP) therapy, which abrogates apnea, in 10 male patients aged 36-69 years old, who were given a diagnosis of OSAS by polysomnography. The percent FMD (%FMD) improved significantly from 3.3+/-0.3% to 5.8+/-0.4% (p<0.01) and 6.6+/-0.3% (p<0.01), before, 1 week, and 4 weeks after nCPAP, respectively. At the same time, the plasma NOx concentrations, metabolites of NO, tended to increase, but the plasma ADMA concentration decreased inversely to %FMD and NOx. A negative correlation between %FMD and plasma ADMA concentration, and a positive correlation between %FMD and plasma NOx concentrations were observed. Nasal CPAP improves endothelial function, in part by the decreasing ADMA concentration, thereby potentiating NO production.

  11. Traffic-related air pollution and alveolar nitric oxide in southern California children.

    PubMed

    Eckel, Sandrah P; Zhang, Zilu; Habre, Rima; Rappaport, Edward B; Linn, William S; Berhane, Kiros; Zhang, Yue; Bastain, Theresa M; Gilliland, Frank D

    2016-05-01

    Mechanisms for the adverse respiratory effects of traffic-related air pollution (TRAP) have yet to be established. We evaluated the acute effects of TRAP exposure on proximal and distal airway inflammation by relating indoor nitric oxide (NO), a marker of TRAP exposure in the indoor microenvironment, to airway and alveolar sources of exhaled nitric oxide (FeNO).FeNO was collected online at four flow rates in 1635 schoolchildren (aged 12-15 years) in southern California (USA) breathing NO-free air. Indoor NO was sampled hourly and linearly interpolated to the time of the FeNO test. Estimated parameters quantifying airway wall diffusivity (DawNO) and flux (J'awNO) and alveolar concentration (CANO) sources of FeNO were related to exposure using linear regression to adjust for potential confounders.We found that TRAP exposure indoors was associated with elevated alveolar NO. A 10 ppb higher indoor NO concentration at the time of the FeNO test was associated with 0.10 ppb higher average CANO (95% CI 0.04-0.16) (equivalent to a 7.1% increase from the mean), 4.0% higher J'awNO (95% CI -2.8-11.3) and 0.2% lower DawNO (95% CI -4.8-4.6).These findings are consistent with an airway response to TRAP exposure that was most marked in the distal airways. Copyright ©ERS 2016.

  12. Alcohol Decreases Organic Dust-Stimulated Airway Epithelial TNF-Alpha Through a Nitric Oxide and Protein Kinase-Mediated Inhibition of TACE.

    PubMed

    Gerald, Carresse L; Romberger, Debra J; DeVasure, Jane M; Khazanchi, Rohan; Nordgren, Tara M; Heires, Art J; Sisson, Joseph H; Wyatt, Todd A

    2016-02-01

    Farm workers in rural areas consume more alcohol than those who reside in urban areas. Occupational exposures such as agricultural work can pose hazards on the respiratory system. It is established that hog barn dust induces inflammation in the airway, including the release of cytokines such as tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and IL-8. We have shown that alcohol alters airway epithelial innate defense through changes in both nitric oxide (NO) and cAMP-dependent protein kinase A (PKA). Simultaneous exposure to hog barn dust and alcohol decreases inflammatory mediators, TNF-α, IL-6, and IL-8, in mice. Previously, mice exposed to both alcohol and hog barn dust showed a depleted amount of lymphocytes compared to mice exposed only to hog barn dust. Weakening of the innate immune response could lead to enhanced susceptibility to disease. In addition, mice that were co-exposed to hog barn dust and alcohol also experienced increased mortality. Because we recently demonstrated that PKA activation inhibits the TNF-α sheddase, TNF-α-converting enzyme (TACE), we hypothesized that an alcohol-mediated PKA pathway blocks TACE activity and prevents the normative inflammatory response to hog barn dust exposure. To delineate these effects, we used PKA pathway inhibitors (adenylyl cyclase [AC], cAMP, and PKA) to modulate the effects of alcohol on dust-stimulated TNF-α release in the bronchial epithelial cell line, BEAS-2B. Alcohol pretreatment blocked TACE activity and TNF-α release in hog barn dust-treated cells. Alcohol continued to block hog barn dust-mediated TNF-α release in the presence of the particulate AC inhibitor, SQ22,536. The soluble adenylyl cyclase inhibitor, KH7, however, significantly increased the inflammatory response to hog barn dust. phosphodiesterase 4 inhibitors significantly elevated cAMP and enhanced alcohol-mediated inhibition of dust-stimulated TNF-α release. In addition, the NO synthase inhibitor, l-NMMA, also reversed

  13. Postexposure Administration of a β2-Agonist Decreases Chlorine-Induced Airway Hyperreactivity in Mice

    PubMed Central

    Song, Weifeng; Wei, Shipeng; Liu, Gang; Yu, Zhihong; Estell, Kim; Yadav, Amit K.; Schwiebert, Lisa M.; Matalon, Sadis

    2011-01-01

    Exposure to chlorine (Cl2) damages airway and alveolar epithelia, resulting in acute lung injury and reactive airway dysfunction syndrome. We evaluated the efficacy and mechanisms by which arformoterol, a long-term β2-agonist, administered after exposure, mitigated the extent of this injury. Exposure of C57BL/6 mice to 400 ppm Cl2 for 30 minutes increased respiratory system resistance and airway responsiveness to aerosolized methacholine (assessed by FlexiVent) up to 6 days after exposure, and decreased Na+-dependent alveolar fluid clearance (AFC). Inducible Nitric Oxide Synthase (iNOS) knockout mice developed similar degrees of airway hyperreactivity as wild-type controls after Cl2 exposure, indicating that reactive intermediates from iNOS do not contribute to Cl2-induced airway dysfunction in our model. Intranasal administration of arformoterol mitigated the Cl2 effects on airway reactivity and AFC, presumably by increasing lung cyclic AMP level. Arformoterol did not modify the inflammatory responses, as evidenced by the number of inflammatory cells and concentrations of IL-6 and TNF-α in the bronchoalveolar lavage. NF-κB activity (assessed by p65 Western blots and electrophoretic mobility shift assay) remained at control levels up to 24 hours after Cl2 exposure. Our results provide mechanistic insight into the effectiveness of long-term β2-agonists in reversing Cl2-induced reactive airway dysfunction syndrome and injury to distal lung epithelial cells. PMID:20855648

  14. Effect of Inhaled β2-Agonist on Exhaled Nitric Oxide in Chronic Obstructive Pulmonary Disease

    PubMed Central

    Amer, Mostafa; Cowan, Jan; Gray, Andrew; Brockway, Ben

    2016-01-01

    The fractional exhaled nitric oxide measured at an expiratory flow of 50mL/s (FENO50) is a marker of airway inflammation, and high levels are associated with greater response to steroid treatment. In asthma, FENO50 increases with bronchodilation and decreases with bronchoconstriction, the latter potentially causing an underestimate of the degree of airway inflammation when asthma worsens. It is unknown whether the same effect occurs in chronic obstructive lung disease (COPD). Likewise, it is not known whether changes in airway calibre in COPD patients alter flow-independent parameters describing pulmonary nitric oxide exchange, such as the maximal flux of nitric oxide (NO) from the proximal airway compartment (J’awNO) and the distal airway/alveolar concentration of NO (CANO). We recruited 24 patients with COPD and performed FENO analysis at multiple expiratory flows before and after treatment with inhaled β2-agonist bronchodilator therapy. For the 21 patients analysed, FENO50 rose from 17.1 (1.4) ppb (geometric mean (geometric SD)) at baseline, to 19.3 (1.3) ppb after bronchodilator therapy, an increase of 2.2 ppb (95% CI, 0.7–3.6; P = 0.005). There were non-significant changes in flow-independent NO parameters. The change in FENO50 correlated positively with the change in J’awNO (rs = 0.67, P < 0.001; rs = 0.62, P = 0.002 before and after correction for axial back-diffusion respectively) following bronchodilation. Inhaled bronchodilator therapy can increase exhaled nitric oxide measurements in COPD. The standardisation of inhaled bronchodilator therapy before FENO analysis in COPD patients should therefore be considered in both research and clinical settings. PMID:27258087

  15. DISTAL MYOPATHIES

    PubMed Central

    Dimachkie, Mazen M.; Barohn, Richard J.

    2014-01-01

    Over a century ago, Gowers described two young patients in whom distal muscles weakness involved the hand, foot, sternocleidomastoid, and facial muscles in the other case the shoulder and distal leg musculature. Soon after, , similar distal myopathy cases were reported whereby the absence of sensory symptoms and of pathologic changes in the peripheral nerves and spinal cord at postmortem examination allowed differentiation from Charcot-Marie-Tooth disease. In 1951, Welander described autosomal dominant (AD) distal arm myopathy in a large Scandanavian cohort. Since then the number of well-characterized distal myopathies has continued to grow such that the distal myopathies have formed a clinically and genetically heterogeneous group of disorders. Affected kindred commonly manifest weakness that is limited to foot and toe muscles even in advanced stages of the disease, with variable mild proximal leg, distal arm, neck and laryngeal muscle involvement in selected individuals. An interesting consequence of the molecular characterization of the distal myopathies has been the recognition that mutation in a single gene can lead to more than one clinical disorder. For example, Myoshi myopathy (MM) and limb girdle muscular dystrophy (LGMD) type 2B are allelic disorders due to defects in the gene that encodes dysferlin. The six well described distal myopathy syndromes are shown in Table 1. Table 2 lists advances in our understanding of the myofibrillar myopathy group and Table 3 includes more recently delineated and less common distal myopathies. In the same manner, the first section of this review pertains to the more traditional six distal myopathies followed by discussion of the myofibrillar myopathies. In the third section, we review other clinically and genetically distinctive distal myopathy syndromes usually based upon single or smaller family cohorts. The fourth section considers other neuromuscular disorders that are important to recognize as they display prominent

  16. Inflammatory Levels of Nitric Oxide Inhibit Airway Epithelial Cell Migration by Inhibition of the Kinase ERK1/2 and Activation of Hypoxia-inducible Factor-1α*S⃞

    PubMed Central

    Bove, Peter F.; Hristova, Milena; Wesley, Umadevi V.; Olson, Nels; Lounsbury, Karen M.; van der Vliet, Albert

    2008-01-01

    Increased synthesis of NO during airway inflammation, caused by induction of nitric-oxide synthase 2 in several lung cell types, may contribute to epithelial injury and permeability. To investigate the consequence of elevated NO production on epithelial function, we exposed cultured monolayers of human bronchial epithelial cells to the NO donor diethylenetriaamine NONOate. At concentrations generating high nanomolar levels of NO, representative of inflammatory conditions, diethylenetriaamine NONOate markedly reduced wound closure in an in vitro scratch injury model, primarily by inhibiting epithelial cell migration. Analysis of signaling pathways and gene expression profiles indicated a rapid induction of the mitogen-activated protein kinase phosphatase (MPK)-1 and decrease in extracellular signal-regulated kinase (ERK)1/2 activation, as well as marked stabilization of hypoxia-inducible factor (HIF)-1α and activation of hypoxia-responsive genes, under these conditions. Inhibition of ERK1/2 signaling using U0126 enhanced HIF-1α stabilization, implicating ERK1/2 dephosphorylation as a contributing mechanism in NO-mediated HIF-1α activation. Activation of HIF-1α by the hypoxia mimic cobalt chloride, or cell transfection with a degradation-resistant HIF-1α mutant construct inhibited epithelial wound repair, implicating HIF-1α in NO-mediated inhibition of cell migration. Conversely, NO-mediated inhibition of epithelial wound closure was largely prevented after small interfering RNA suppression of HIF-1α. Finally, NO-mediated inhibition of cell migration was associated with HIF-1α-dependent induction of PAI-1 and activation of p53, both negative regulators of epithelial cell migration. Collectively, our results demonstrate that inflammatory levels of NO inhibit epithelial cell migration, because of suppression of ERK1/2 signaling, and activation of HIF-1α and p53, with potential consequences for epithelial repair and remodeling during airway inflammation. PMID

  17. Effect of nasal steroid treatment on airway inflammation determined by exhaled nitric oxide in allergic schoolchildren with perennial rhinitis and asthma.

    PubMed

    Pedroletti, Christophe; Lundahl, Joachim; Alving, Kjell; Hedlin, Gunilla

    2008-05-01

    Rhinitis is common in asthmatic schoolchildren who are allergic to animal dander and constantly and indirectly exposed to these allergens in their everyday environment. As a patho-physiological linkage between nasal and bronchial inflammation has been proposed to exist, the primary objective of this study was to determine whether nasal administration of mometasone furoate (MSNF) can reduce bronchial inflammation, as reflected in the level of exhaled nitric oxide (F(E)NO) in asthmatic schoolchildren with dander allergy and mild-to-moderate rhinitis. Forty such children were assigned randomly to be treated for 4 wk with MSNF or placebo, employing a double-blind procedure. F(E)NO was the primary end-point measured and secondary end-points were nasal levels of NO, the concentration of eosinophilic cationic protein (ECP) in nasal lavage, the relative numbers of eosinophils in blood, forced expiratory volume in 1 s (FEV(1)), peak expiratory flow (PEF) and scoring of symptoms. There was no significant difference in the F(E)NO values of the treated and control groups at any time-point, whereas the nasal level of ECP was lower in the treated group compared with placebo (p = 0.05) on both days 7 and 28, and compared with baseline for the treated group (p = 0.06 on day 7, p = 0.02 on day 28). Furthermore, the mean blood eosinophil count decreased in the treated group, which also demonstrated lower scores for nasal symptoms compared with placebo, but neither of these differences were statistically significant. FEV(1), PEF and nasal levels of NO remained unchanged in both groups. Four weeks of nasal treatment with MSNF had no effect on bronchial inflammation, as reflected by exhaled NO, whereas signs of nasal and systemic eosinophil activation were reduced. Thus, nasal administration of a steroid as a strategy to reduce asthmatic inflammation remains questionable in mild-to-moderately severe cases of perennial rhinitis and asthma.

  18. Surgical Airway

    PubMed Central

    Patel, Sapna A; Meyer, Tanya K

    2014-01-01

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

  19. Toll-like Receptor 7 Rapidly Relaxes Human Airways

    PubMed Central

    Scott, Gregory D.; Proskocil, Becky J.; Fryer, Allison D.; Jacoby, David B.; Kaufman, Elad H.

    2013-01-01

    Rationale: Toll-like receptors (TLRs) 7 and 8 detect respiratory virus single-stranded RNA and trigger an innate immune response. We recently described rapid TLR7-mediated bronchodilation in guinea pigs. Objectives: To characterize TLR7 expression and TLR7-induced airway relaxation in humans and in eosinophilic airway inflammation in guinea pigs. To evaluate the relaxant effects of other TLRs. Methods: Human airway smooth muscle strips were contracted with methacholine in vitro, and responses to TLR7 and TLR8 agonists were assessed. TLR7-mediated nitric oxide production was measured using a fluorescent indicator, and TLR7 expression was characterized using immunofluorescence. TLR7 signaling was also evaluated in ovalbumin-challenged guinea pigs. Measurements and Main Results: The TLR7 agonist imiquimod (R837) caused rapid dose-dependent relaxation of methacholine-contracted human airways in vitro. This was blocked by the TLR7 antagonist IRS661 and by inhibiting nitric oxide production but not by inhibiting prostaglandin production. TLR7 activation markedly increased fluorescence of a nitric oxide detector. TLR7 was expressed on airway nerves, but not airway smooth muscle, implicating airway nerves as the source of TLR7-induced nitric oxide production. TLR7-mediated relaxation persisted in inflamed guinea pigs airways in vivo. The TLR8 agonists polyuridylic acid and polyadenylic acid also relaxed human airways, and this was not blocked by the TLR7 antagonist or by blocking nitric oxide or prostaglandin production. No other TLRs relaxed the airways. Conclusions: TLR7 is expressed on airway nerves and mediates relaxation of human and animal airways through nitric oxide production. TLR7-mediated bronchodilation may be a new therapeutic strategy in asthma. PMID:23924358

  20. Nitric oxide and the common cold.

    PubMed

    Proud, David

    2005-02-01

    The common cold is a clinical syndrome triggered by a variety of viral pathogens, but rhinoviruses are the most frequent cause. Complications of such infections include sinusitis, otitis media, and exacerbations of asthma and chronic obstructive lung disease. There is growing interest in host innate defence responses that may regulate the severity of viral responses. We will review recent evidence that nitric oxide is an important contributor to the host response during colds. Infection of human airway epithelial cells with human rhinovirus has been shown to lead to the increased expression of inducible nitric oxide synthase both in vitro and in vivo. This increase in epithelial inducible nitric oxide synthase correlates with increased levels of nitric oxide in exhaled air. Importantly, nitric oxide can inhibit human rhinovirus-induced epithelial expression of several pro-inflammatory cytokines and can inhibit viral replication in epithelial cells in vitro. Moreover, nitric oxide can modulate several signal transduction pathways that are associated with cytokine generation. Nitric oxide can also nitrosylate viral proteases and can interact with the immune system. Consistent with these observations, pilot studies have indicated that the increased generation of nitric oxide during rhinovirus infections is associated with fewer symptoms and more rapid viral clearance. Further studies are warranted to evaluate the role of nitric oxide in colds and to determine whether the administration of nitric oxide donor compounds could be a viable therapeutic approach for viral exacerbations of airway diseases.

  1. Exhaled nitric oxide in children after accidental exposure to chlorine gas.

    PubMed

    Grasemann, Hartmut; Tschiedel, Eva; Groch, Manuela; Klepper, Jörg; Ratjen, Felix

    2007-08-01

    Chronic exposure to chlorine gas has been shown to cause occupational asthma. Acute inhalation of chlorine is known to cause airway inflammation and induce airway nitric oxide formation. Exhaled nitric oxide may therefore be a marker of airway damage after chlorine gas exposure. After accidental chlorine gas exposure in a swimming pool, exhaled nitric oxide and pulmonary function were repeatedly measured in 18 children over a 1-mo period. Symptomatic children with impaired pulmonary function had higher nitric oxide levels on the day after the exposure compared to day 8 and day 28. Differences in exhaled nitric oxide were more pronounced at a higher exhalation flow compared to lower flow, suggesting peripheral rather than central airway damage. This was in accordance with the observed changes in pulmonary function. No changes in exhaled nitric oxide were seen in asymptomatic children. These data suggest that acute chlorine gas exposure results in a mild increase of exhaled nitric oxide in symptomatic children.

  2. Ventilation heterogeneity is a major determinant of airway hyperresponsiveness in asthma, independent of airway inflammation

    PubMed Central

    Downie, Sue R; Salome, Cheryl M; Verbanck, Sylvia; Thompson, Bruce; Berend, Norbert; King, Gregory G

    2007-01-01

    Background Airway hyperresponsiveness is the ability of airways to narrow excessively in response to inhaled stimuli and is a key feature of asthma. Airway inflammation and ventilation heterogeneity have been separately shown to be associated with airway hyperresponsiveness. A study was undertaken to establish whether ventilation heterogeneity is associated with airway hyperresponsiveness independently of airway inflammation in subjects with asthma and to determine the effect of inhaled corticosteroids on this relationship. Methods Airway inflammation was measured in 40 subjects with asthma by exhaled nitric oxide, ventilation heterogeneity by multiple breath nitrogen washout and airway hyperresponsiveness by methacholine challenge. In 18 of these subjects with uncontrolled symptoms, measurements were repeated after 3 months of treatment with inhaled beclomethasone dipropionate. Results At baseline, airway hyperresponsiveness was independently predicted by airway inflammation (partial r2 = 0.20, p<0.001) and ventilation heterogeneity (partial r2 = 0.39, p<0.001). Inhaled corticosteroid treatment decreased airway inflammation (p = 0.002), ventilation heterogeneity (p = 0.009) and airway hyperresponsiveness (p<0.001). After treatment, ventilation heterogeneity was the sole predictor of airway hyperresponsiveness (r2 = 0.64, p<0.001). Conclusions Baseline ventilation heterogeneity is a strong predictor of airway hyperresponsiveness, independent of airway inflammation in subjects with asthma. Its persistent relationship with airway hyperresponsiveness following anti‐inflammatory treatment suggests that it is an important independent determinant of airway hyperresponsiveness. Normalisation of ventilation heterogeneity is therefore a potential goal of treatment that may lead to improved long‐term outcomes. PMID:17311839

  3. [Mechanisms of non-specific airway hyperresponsiveness: Methacholine-induced alterations in airway architecture].

    PubMed

    Plantier, L; Pradel, A; Delclaux, C

    2016-10-01

    Multiple mechanisms drive non-specific airway hyperresponsiveness in asthma. At the organ level, methacholine inhalation induces a complex bronchomotor response involving both bronchoconstriction and, to some extent, paradoxical bronchodilatation. This response is heterogeneous both serially, along a single bronchial axis, and in parallel, among lung regions. The bronchomotor response to methacholine induces contraction of distal airways as well as focal airway closure in select lung territories, leading to anatomically defined ventilation defects and decreased vital capacity. In addition, loss of the bronchoprotector and bronchodilator effects of deep inspirations is a key contributor to airway hyperresponsiveness in asthma. Copyright © 2015 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  4. 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

  5. [Nitric oxide].

    PubMed

    Rovira, I

    1995-01-01

    Nitric oxide was identified as the relaxing factor derived from the endothelium in 1987. Nitric oxide synthesis allows the vascular system to maintain a state of vasodilation, thereby regulating arterial pressure. Nitric oxide is also found in platelets, where it inhibits adhesion and aggregation; in the immune system, where it is responsible for the cytotoxic action of macrophages; and in the nervous system, where it acts as neurotransmitter. A deficit in endogenous synthesis of nitric oxide contributes to such conditions as essential arterial hypertension, pulmonary hypertension and heart disease. An excess of nitrous oxide induced by endotoxins and cytokinins, meanwhile, is believed to be responsible for hypotension in septic shock and for hyperdynamic circulatory state in cirrhosis of the liver. Nitric oxide has also been implicated in the rejection of transplanted organs and in cell damage after reperfusion. Inhaled nitrous oxide gas reduces pulmonary hypertension without triggering systemic hypotension in both experimental and clinical conditions. It also produces selective vasodilation when used to ventilate specific pulmonary areas, thereby improving the ventilation/perfusion ratio and, hence, oxygenation. Nitric oxide inhalation is effective in pulmonary hypertension-coincident with chronic obstructive lung disease, in persistent neonatal pulmonary hypertension and in pulmonary hypertension with congenital or acquired heart disease. Likewise, it reduces intrapulmonary shunt in acute respiratory failure and improves gas exchange. Under experimental conditions nitric oxide acts as a bronchodilator, although it seems to be less effective for this purpose in clinical use.(ABSTRACT TRUNCATED AT 250 WORDS)

  6. Inhaled nitric oxide in chronic obstructive lung disease

    SciTech Connect

    Tiihonen, J.; Hakola, P.; Paanila, J.; Turtiainen . Dept. of Forensic Psychiatry)

    1993-01-30

    During an investigation of the effect of nitric oxide on the pulmonary circulation the authors had the opportunity to give nitric oxide to a patient with longstanding obstructive airway disease, with successful results. A 72-year-old man with chronic obstructive pulmonary disease was referred to the institution for assessment of pulmonary vascular reactivity to acetylcholine and nitric oxide. Acetylcholine was infused into the main pulmonary artery followed 15 min later by an inhalation of 80 parts per million (ppm) nitric oxide. Heart rate and systemic arterial and pulmonary arterial pressures were continuously monitored. Throughout the study the inspired oxygen concentration was kept constant at 98%. Nitrogen dioxide and nitric oxide concentrations were monitored while nitric oxide was delivered. The infusion of acetylcholine resulted in a small increase in pulmonary artery pressure and pulmonary vascular resistance. Nitric oxide produced a substantial fall in pulmonary artery pressure and pulmonary vascular resistance with a concomitant increase in systemic arterial oxygen tension. These results suggest that endothelium-dependent relaxation of the pulmonary vasculature was impaired in the patient and that exogenous nitric oxide was an effective pulmonary vasodilator. In-vitro investigation of explanted airways disease suggests not only that endothelium-dependent pulmonary artery relaxation is impaired but also that the dysfunction is related to pre-existing hypoxemia and hypercapnia. Nitric oxide inhibits proliferation of cultured vascular smooth muscle cells and might alter the pulmonary vascular remodeling characteristic of patients with chronic obstructive airways disease.

  7. Role of exhaled nitric oxide in asthma.

    PubMed

    Yates, D H

    2001-04-01

    Nitric oxide (NO), an evanescent atmospheric gas, has recently been discovered to be an important biological mediator in animals and humans. Nitric oxide plays a key role within the lung in the modulation of a wide variety of functions including pulmonary vascular tone, nonadrenergic non-cholinergic (NANC) transmission and modification of the inflammatory response. Asthma is characterized by chronic airway inflammation and increased synthesis of NO and other highly reactive and toxic substances (reactive oxygen species). Pro- inflammatory cytokines such as TNFalpha and IL-1beta are secreted in asthma and result in inflammatory cell recruitment, but also induce calcium- and calmodulin-independent nitric oxide synthases (iNOS) and perpetuate the inflammatory response within the airways. Nitric oxide is released by several pulmonary cells including epithelial cells, eosinophils and macrophages, and NO has been shown to be increased in conditions associated with airway inflammation, such as asthma and viral infections. Nitric oxide can be measured in the expired air of several species, and exhaled NO can now be rapidly and easily measured by the use of chemiluminescence analysers in humans. Exhaled NO is increased in steroid-naive asthmatic subjects and during an asthma exacerbation, although it returns to baseline levels with appropriate anti-inflammatory treatment, and such measurements have been proposed as a simple non-invasive method of measuring airway inflammation in asthma. Here the chemical and biological properties of NO are briefly discussed, followed by a summary of the methodological considerations relevant to the measurement of exhaled NO and its role in lung diseases including asthma. The origin of exhaled NO is considered, and brief mention made of other potential markers of airway inflammation or oxidant stress in exhaled breath.

  8. 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.

  9. Distal esophageal spasm: an update.

    PubMed

    Achem, Sami R; Gerson, Lauren B

    2013-09-01

    Distal esophageal spasm (DES) is an esophageal motility disorder that presents clinically with chest pain and/or dysphagia and is defined manometrically as simultaneous contractions in the distal (smooth muscle) esophagus in ≥20% of wet swallows (and amplitude contraction of ≥30 mmHg) alternating with normal peristalsis. With the introduction of high resolution esophageal pressure topography (EPT) in 2000, the definition of DES was modified. The Chicago classification proposed that the defining criteria for DES using EPT should be the presence of at least two premature contractions (distal latency<4.5 s) in a context of normal EGJ relaxation. The etiology of DES remains insufficiently understood, but evidence links nitric oxide (NO) deficiency as a culprit resulting in a disordered neural inhibition. GERD frequently coexists in DES, and its role in the pathogenesis of symptoms needs further evaluation. There is some evidence from small series that DES can progress to achalasia. Treatment remains challenging due in part to lack of randomized placebo-controlled trials. Current treatment agents include nitrates (both short and long acting), calcium-channel blockers, anticholinergic agents, 5-phosphodiesterase inhibitors, visceral analgesics (tricyclic agents or SSRI), and esophageal dilation. Acid suppression therapy is frequently used, but clinical outcome trials to support this approach are not available. Injection of botulinum toxin in the distal esophagus may be effective, but further data regarding the development of post-injection gastroesophageal reflux need to be assessed. Heller myotomy combined with fundoplication remains an alternative for the rare refractory patient. Preliminary studies suggest that the newly developed endoscopic technique of per oral endoscopic myotomy (POEM) may also be an alternative treatment modality.

  10. Differential bronchodilatory effects of terbutaline, diltiazem, and aminophylline in canine intraparenchymal airways.

    PubMed

    Akhtar, S; Mazzeo, A J; Cheng, E Y; Bosnjak, Z; Kampine, J P

    1999-08-01

    Intraparenchymal airways are involved in air flow regulation. Relaxation of intraparenchymal airways to volatile anesthetics varied by topographic location. This study was conducted to determine whether other bronchodilators (terbutaline, diltiazem, and aminophylline) relax bronchiolus to a greater degree than bronchus, as seen with volatile anesthetics. In vitro, controlled, randomized study. Animal research laboratory. Adult dogs (n = 9). Proximal (outer diameter, 4-6 mm) and distal (outer diameter, 0.8-1.5 mm) airway rings of dogs were contracted in tissue baths with the effective concentration of acetylcholine that produces half the maximum response. Airway relaxant dose-response curves were constructed to measure isometric tension after administration of terbutaline (concentration range, 10(-8) to 10(-4) M), diltiazem (concentration range, 3 x 10(-7) to 1 x 10(-4) M), and aminophylline (concentration range, 10(-7) to 10(-4) M). All three bronchodilators caused relaxation of the proximal and distal airways. At the maximum dose, diltiazem (maximum relaxation, 95%+/-2% [proximal], 94%+/-6% [distal]; p > .05) was the most efficacious, followed by terbutaline (maximum relaxation, 72%+/-13% [proximal], 55%+/-9% [distal]; p < .05) and aminophylline (maximum relaxation, 32%+/-10% [proximal], 35%+/-18% [distal]; p > .05. At the concentrations tested, they were equally efficacious. No significant differences in relaxation between proximal and distal airways were noted with diltiazem or aminophylline in the entire dose range. However, terbutaline relaxed the distal airway more than the proximal airway in the entire dose range. The results demonstrate that only terbutaline showed a differential airway relaxant effect between proximal and distal airways, as seen with volatile anesthetics.

  11. Distal Convoluted Tubule

    PubMed Central

    Ellison, David H.

    2014-01-01

    The distal convoluted tubule is the nephron segment that lies immediately downstream of the macula densa. Although short in length, the distal convoluted tubule plays a critical role in sodium, potassium, and divalent cation homeostasis. Recent genetic and physiologic studies have greatly expanded our understanding of how the distal convoluted tubule regulates these processes at the molecular level. This article provides an update on the distal convoluted tubule, highlighting concepts and pathophysiology relevant to clinical practice. PMID:24855283

  12. Nitric oxide

    Integrated Risk Information System (IRIS)

    Nitric oxide ; CASRN 10102 - 43 - 9 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic Ef

  13. The Phillips airway.

    PubMed

    Haridas, R P; Wilkinson, D J

    2012-07-01

    The Phillips airway was developed by George Ramsay Phillips. There is no known original description of the airway and the earliest known reference to it is from 1919. The airway and its modifications are described.

  14. Vanishing Bronchus After Lung Transplantation: The Role of Sequential Airway Dilatations

    PubMed Central

    Alraiyes, Abdul Hamid; Inaty, Hanine; Machuzak, Michael S.

    2017-01-01

    Background: Airway complications after lung transplant play an important role in patient survival. Early recognition and treatment of these complications are necessary to help ensure that patients who receive lung transplants have good outcomes. Case Report: A 61-year-old female with a history of pulmonary venous occlusive disease presented to our hospital for a double-lung transplant. Her postoperative course was complicated by severe primary graft dysfunction. Airway examination showed significant mucosal ischemia distal to the anastomosis bilaterally with diffuse narrowing of all distal bronchial segments. Repeat bronchoscopies with debridement of necrotic material and balloon dilatation of stenotic airways were performed to maintain airway patency. Conclusion: Post–lung transplant airway necrosis and stenosis mandate early identification and treatment. Repetitive bronchoscopies with sequential balloon dilatations are mandatory to prevent future airway stenosis and airway vanishing. PMID:28331451

  15. Transcriptional Regionalization of the Fruit Fly’s Airway Epithelium

    PubMed Central

    Faisal, Muhammad N.; Hoffmann, Julia; El-Kholy, Samar; Kallsen, Kimberley; Wagner, Christina; Bruchhaus, Iris; Fink, Christine; Roeder, Thomas

    2014-01-01

    Although airway epithelia are primarily devoted to gas exchange, they have to fulfil a number of different tasks including organ maintenance and the epithelial immune response to fight airborne pathogens. These different tasks are at least partially accomplished by specialized cell types in the epithelium. In addition, a proximal to distal gradient mirroring the transition from airflow conduction to real gas exchange, is also operative. We analysed the airway system of larval Drosophila melanogaster with respect to region-specific expression in the proximal to distal axis. The larval airway system is made of epithelial cells only. We found differential expression between major trunks of the airways and more distal ones comprising primary, secondary and terminal ones. A more detailed analysis was performed using DNA-microarray analysis to identify cohorts of genes that are either predominantly expressed in the dorsal trunks or in the primary/secondary/terminal branches of the airways. Among these differentially expressed genes are especially those involved in signal transduction. Wnt-signalling associated genes for example are predominantly found in secondary/terminal airways. In addition, some G-protein coupled receptors are differentially expressed between both regions of the airways, exemplified by those activated by octopamine or tyramine, the invertebrate counterparts of epinephrine and norepinephrine. Whereas the OAMB is predominantly found in terminal airway regions, the oct3βR has higher expression levels in dorsal trunks. In addition, we observed a significant association of both, genes predominantly expressed in dorsal trunks or in primary to terminal branches branches with those regulated by hypoxia. Taken together, this observed differential expression is indicative for a proximal to distal transcriptional regionalization presumably reflecting functional differences in these parts of the fly’s airway system. PMID:25020150

  16. Nitric oxide synthase in tiger salamander retina.

    PubMed

    Kurenni, D E; Thurlow, G A; Turner, R W; Moroz, L L; Sharkey, K A; Barnes, S

    1995-10-23

    Previous studies have indicated that nitric oxide, a labile freely diffusible biological messenger synthesized by nitric oxide synthase, may modulate light transduction and signal transmission in the retina. In the present work, the large size of retinal cells in tiger salamander (Ambystoma tigrinum) allowed the utilization of nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase histochemistry and nitric oxide synthase immunocytochemistry to delineate the cell-specific intracellular localization of nitric oxide synthase. NADPH-diaphorase activity was highly concentrated in the outer retina, in rod and cone inner segment ellipsoids, and between and adjacent to the photoreceptor cell bodies in the outer nuclear layer. Examination of enzymatically isolated retinal cells indicated that outer nuclear layer NADPH-diaphorase activity was localized to the distal processes of the retinal glial (Müller) cells and to putative bipolar cell Landolt clubs. Less intense NADPH-diaphorase activity was seen in the photoreceptor inner segment myoid region, in a small number of inner nuclear layer cells, in cap-like configurations at the distal poles of cells in the ganglion cell layer and surrounding ganglion cell layer somata, and in punctate form within both plexiform layers, the pigment epithelium, and the optic nerve. Nitric oxide synthase-like immunoreactivity was similarly localized, but was also concentrated along a thin sublamina centered within the inner plexiform layer. The potential for nitric oxide generation at multiple retinal sites suggests that this molecule may play a number of roles in the processing of visual information in the retina.

  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. Taste Receptors in Upper Airway Immunity.

    PubMed

    Carey, Ryan M; Lee, Robert J; Cohen, Noam A

    2016-01-01

    Taste receptors are well known for their role in communicating information from the tongue to the brain about nutritional value or potential toxicity of ingested substances. More recently, it has been shown that taste receptors are expressed in other locations throughout the body, including the airway, gastrointestinal tract, brain and pancreas. The roles of some 'extraoral' taste receptors are largely unknown, but emerging research suggests that bitter and sweet taste receptors in the airway are capable of sensing bacteria and modulating innate immunity. This chapter focuses on the role of bitter and sweet taste receptors in human airway innate immunity and their clinical relevance to rhinosinusitis. The bitter taste receptor T2R38 expressed in sinonasal cilia detects bitter bacterial quorum-sensing molecules and activates a nitric oxide-dependent innate immune response; moreover, there are polymorphisms in T2R38 that underlie susceptibility to chronic rhinosinusitis (CRS). Bitter and sweet receptors in sinonasal solitary chemosensory cells control secretion of antimicrobial peptides in the upper airway and may have a profound impact on airway infections in patients with CRS and diabetes. Future research on taste receptors in the airway has enormous potential to expand our understanding of host-pathogen immune interactions and provide novel therapeutic targets.

  19. Anaesthetic management in thoracoscopic distal tracheal resection.

    PubMed

    Acosta Martínez, J; Beato López, J; Domínguez Blanco, A; López Romero, J L; López Villalobos, J L

    2017-03-01

    Surgical resection of tracheal tumours, especially distal tracheal tumours, is a challenge for the anaesthesiologists involved, mainly due to difficulties in ensuring adequate control of the airway and ventilation. We report the case of a patient undergoing tracheal resection and anastomosis by VATS, emphasizing the anaesthetic management. Copyright © 2016 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

  20. The role bronchoscopy in the diagnosis of airway disease in children

    PubMed Central

    Soyer, Tutku

    2016-01-01

    Bronchoscopy is endoscopic examination of airways that allows both diagnostic and interventional procedures in the evaluation of airway disease in children. It can be performed with either rigid or flexible instruments, depending on the particular needs of patients and skills of bronchoscopist. In addition to visualization of airways, bronchoscopy enables to obtain specimens from lungs and distal airways. Bronchoalveolar lavage (BAL) yields samples from surfaces of the alveoli and aids differential diagnosis of various pulmonary disease. Foreign body removal and examination of anatomy and dynamics of airways are also common indications of bronchoscopy in children. Improvement in the technology, endoscopic instrumentation allows detailed evaluation and interventional manipulation of airway lesions in small children. Although bronchoscopy is considered as a safe procedure, obstruction of airway may challenge and require special endoscopic skills with appropriate instrumentation. This review is aimed to outline the role of bronchoscopy in diagnosis airway disease in children. PMID:28066622

  1. Triggers of airway inflammation.

    PubMed

    Kerrebijn, K F

    1986-01-01

    Most asthmatics have hyperresponsive airways. This makes them more sensitive than non-asthmatics to bronchoconstricting environmental exposures which, in their turn, may enhance responsiveness. Airway inflammation is considered to be a key determinant of airway hyperresponsiveness: the fact that chronic airway inflammation in cystic fibrosis does not lead to airway hyperresponsiveness of any importance indicates, however, that the role of airway inflammation is complex and incompletely elucidated. The main inducers of airway inflammation are viral infections, antigens, occupational stimuli and pollutants. Although exercise, airway cooling and hyper- or hypotonic aerosols are potent stimuli of bronchoconstriction, it is questionable if airway inflammation is involved in their mode of action. Each of the above-mentioned stimuli is discussed, with emphasis laid on the relation of symptoms to mechanisms.

  2. Airway-parenchymal interdependence

    PubMed Central

    Paré, Peter D; Mitzner, Wayne

    2015-01-01

    In this manuscript we discuss the interaction of the lung parenchyma and the airways as well as the physiological and pathophysiological significance of this interaction. These two components of the respiratory organ can be thought of as two independent elastic structures but in fact the mechanical properties of one influence the behavior of the other. Traditionally the interaction has focused on the effects of the lung on the airways but there is good evidence that the opposite is also true, i.e., that the mechanical properties of the airways influence the elastic properties of the parenchyma. The interplay between components of the respiratory system including the airways, parenchyma and vasculature is often referred to as “interdependence.” This interdependence transmits the elastic recoil of the lung to create an effective pressure that dilates the airways as transpulmonary pressure and lung volume increase. By using a continuum mechanics analysis of the lung parenchyma, it is possible to predict the effective pressure between the airways and parenchyma, and these predictions can be empirically evaluated. Normal airway caliber is maintained by this pressure in the adventitial interstitium of the airway, and it counteracts airway compression during forced expiration as well as the ability of airway smooth muscle to narrow airways. Interdependence has physiological and pathophysiological significance. Weakening of the forces of interdependence contributes to airway dysfunction and gas exchange impairment in acute and chronic airway diseases including asthma and emphysema. PMID:23723029

  3. Distal median nerve dysfunction

    MedlinePlus

    ... Distal median nerve dysfunction is a form of peripheral neuropathy that affects the movement of or sensation in ... and the A.D.A.M. Editorial team. Peripheral Nerve Disorders Read more Latest Health News Read more Health ...

  4. Transphyseal Distal Humerus Fracture.

    PubMed

    Abzug, Joshua; Ho, Christine Ann; Ritzman, Todd F; Brighton, Brian

    2016-01-01

    Transphyseal distal humerus fractures typically occur in children younger than 3 years secondary to birth trauma, nonaccidental trauma, or a fall from a small height. Prompt and accurate diagnosis of a transphyseal distal humerus fracture is crucial for a successful outcome. Recognizing that the forearm is not aligned with the humerus on plain radiographs may aid in the diagnosis of a transphyseal distal humerus fracture. Surgical management is most commonly performed with the aid of an arthrogram. Closed reduction and percutaneous pinning techniques similar to those used for supracondylar humerus fractures are employed. Cubitus varus caused by a malunion, osteonecrosis of the medial condyle, or growth arrest is the most common complication encountered in the treatment of transphyseal distal humerus fractures. A corrective lateral closing wedge osteotomy can be performed to restore a nearly normal carrying angle.

  5. Distal ulnar growth arrest.

    PubMed

    Nelson, O A; Buchanan, J R; Harrison, C S

    1984-03-01

    Four cases of arrest of distal ulnar physeal growth occurring in children ages 7 to 13 years had follow-up for 2 to 10 years. Each patient developed bowing of the radial diaphysis, ulnar translation of the distal radial epiphysis, and increased ulnar angulation of the distal radiocarpal joint surface. Growth discrepancies were documented in both the ulna (range 2.2 to 3.9 cm) and to a lesser extent the radius (range 0.2 to 1.6 cm) when compared to the opposite forearm in each patient. The progression of deformity appeared to be greatest during adolescence. Radial deviation and pronation were limited to varying degrees in each case. No patient had significant pain or functional impairment, but the cosmetic appearance was always displeasing. Indications for surgical treatment include increasing ulnar angulation of the distal radial articular surface, progressive loss of motion, and displeasing cosmetic appearance.

  6. Distal renal tubular acidosis

    MedlinePlus

    ... get better with treatment. When to Contact a Medical Professional Call your health care provider if you have symptoms of distal renal tubular acidosis. Get medical help right away if you develop emergency symptoms ...

  7. Airway epithelium-derived relaxing factor: myth, reality, or naivety?

    PubMed

    Vanhoutte, Paul M

    2013-05-01

    The presence of a healthy epithelium can moderate the contraction of the underlying airway smooth muscle. This is, in part, because epithelial cells generate inhibitory messages, whether diffusible substances, electrophysiological signals, or both. The epithelium-dependent inhibitory effect can be tonic (basal), synergistic, or evoked. Rather than a unique epithelium-derived relaxing factor (EpDRF), several known endogenous bronchoactive mediators, including nitric oxide and prostaglandin E2, contribute. The early concept that EpDRF diffuses all the way through the subepithelial layers to directly relax the airway smooth muscle appears unlikely. It is more plausible that the epithelial cells release true messenger molecules, which alter the production of endogenous substances (nitric oxide and/or metabolites of arachidonic acid) by the subepithelial layers. These substances then diffuse to the airway smooth muscle cells, conveying epithelium dependency.

  8. Upper airway biopsy

    MedlinePlus

    ... upper airway Images Upper airway test Bronchoscopy Throat anatomy References Yung RC, Boss EF. Tracheobronchial endoscopy. In: Flint PW, Haughey BH, Lund LJ, et al, eds. Cummings Otolaryngology: Head & Neck Surgery. 5th ed. Philadelphia, PA: Elsevier Mosby; ...

  9. Caveolin-1 knockout mice exhibit airway hyperreactivity

    PubMed Central

    Aravamudan, Bharathi; VanOosten, Sarah K.; Meuchel, Lucas W.; Vohra, Pawan; Thompson, Michael; Sieck, Gary C.; Prakash, Y. S.

    2012-01-01

    Caveolae are flask-shaped plasma membrane invaginations expressing the scaffolding caveolin proteins. Although caveolins have been found in endothelium and epithelium (where they regulate nitric oxide synthase activity), their role in smooth muscle is still under investigation. We and others have previously shown that caveolae of human airway smooth muscle (ASM), which express caveolin-1, contain Ca2+ and force regulatory proteins and are involved in mediating the effects of inflammatory cytokines such as TNF-α on intracellular Ca2+ concentration responses to agonist. Accordingly, we tested the hypothesis that in vivo, absence of caveolin-1 leads to reduced airway hyperresponsiveness, using a knockout (KO) (Cav1 KO) mouse and an ovalbumin-sensitized/challenged (OVA) model of allergic airway hyperresponsiveness. Surprisingly, airway responsiveness to methacholine, tested by use of a FlexiVent system, was increased in Cav1 KO control (CTL) as well as KO OVA mice, which could not be explained by a blunted immune response to OVA. In ASM of wild-type (WT) OVA mice, expression of caveolin-1, the caveolar adapter proteins cavins 1–3, and caveolae-associated Ca2+ and force regulatory proteins such as Orai1 and RhoA were all increased, effects absent in Cav1 KO CTL and OVA mice. However, as with WT OVA, both CTL and OVA Cav1 KO airways showed signs of enhanced remodeling, with high expression of proliferation markers and increased collagen. Separately, epithelial cells from airways of all three groups displayed lower endothelial but higher inducible nitric oxide synthase and arginase expression. Arginase activity was also increased in these three groups, and the inhibitor nor-NOHA (N-omega-nor-l-arginine) enhanced sensitivity of isolated tracheal rings to ACh, especially in Cav1 KO mice. On the basis of these data disproving our original hypothesis, we conclude that caveolin-1 has complex effects on ASM vs. epithelium, resulting in airway hyperreactivity in vivo mediated

  10. Careers in Airway Science.

    ERIC Educational Resources Information Center

    Federal Aviation Administration (DOT), Washington, DC.

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

  11. Airway-parenchymal interdependence.

    PubMed

    Paré, Peter D; Mitzner, Wayne

    2012-07-01

    In this article, we discuss the interaction of the lung parenchyma and the airways as well as the physiological and pathophysiological significance of this interaction. These two components of the respiratory organ can be thought of as two independent elastic structures but in fact the mechanical properties of one influence the behavior of the other. Traditionally, the interaction has focused on the effects of the lung on the airways but there is good evidence that the opposite is also true, that is, that the mechanical properties of the airways influence the elastic properties of the parenchyma. The interplay between components of the respiratory system including the airways, parenchyma, and vasculature is often referred to as "interdependence." This interdependence transmits the elastic recoil of the lung to create an effective pressure that dilates the airways as transpulmonary pressure and lung volume increase. By using a continuum mechanics analysis of the lung parenchyma, it is possible to predict the effective pressure between the airways and parenchyma, and these predictions can be empirically evaluated. Normal airway caliber is maintained by this pressure in the adventitial interstitium of the airway, and it attenuates the ability of airway smooth muscle to narrow airways. Interdependence has physiological and pathophysiological significance. Weakening of the forces of interdependence contributes to airway dysfunction and gas exchange impairment in acute and chronic airway diseases including asthma and emphysema. © 2012 American Physiological Society. Compr Physiol 2:1853-1872, 2012.

  12. The bone morphogenic protein antagonist gremlin regulates proximal-distal patterning of the lung.

    PubMed

    Lu, M M; Yang, H; Zhang, L; Shu, W; Blair, D G; Morrisey, E E

    2001-12-01

    The proximal-distal patterning of lung epithelium involves a complex series of signaling and transcriptional events resulting in the programmed differentiation of highly specialized cells for gas exchange and surfactant protein expression essential for postnatal lung function. The BMP signaling pathway has been shown to regulate cellular differentiation in the lung as well as other tissues. In this report, we show that the can family of related BMP antagonists, including gremlin, cer-1, PRDC, and Dan are expressed in the lung during embryonic development with gremlin expression observed in the proximal airway epithelium. The role of gremlin in lung development was explored by overexpressing it in the distal lung epithelium of transgenic mice using the human SP-C promoter. SP-C/gremlin transgenic mice exhibited a disruption of the proximal-distal patterning found in the airways of the mammalian lung. Expanded expression of the proximal epithelial cell markers CC10 and HFH-4 (Foxj1) was observed in the distal regions of transgenic lungs. Furthermore, smooth muscle alpha-actin expression was observed surrounding the distal airways of SP-C/gremlin mice, indicating a proximalization of distal lung tubules. These data suggest that gremlin plays an important role in lung morphogenesis by regulating the proximal-distal patterning of the lung during development. Copyright 2001 Wiley-Liss, Inc.

  13. Dilemmas, Confusion, and Misconceptions Related to Small Airways Directed Therapy.

    PubMed

    Lavorini, Federico; Pedersen, Søren; Usmani, Omar S

    2017-06-01

    During the past decade, there has been increasing evidence that the small airways (ie, airways < 2 mm in internal diameter) contribute substantially to the pathophysiologic and clinical expression of asthma and COPD. The increased interest in small airways is, at least in part, a result of innovation in small-particle aerosol formulations that better target the distal lung and also advanced physiologic methods of assessing small airway responses. Increasing the precision of drug deposition may improve targeting of specific diseases or receptor locations, decrease airway drug exposure and adverse effects, and thereby increase the efficiency and effectiveness of inhaled drug delivery. The availability of small-particle aerosols of corticosteroids, bronchodilators, or their combination enables a higher total lung deposition and better peripheral lung penetration and provides added clinical benefit, compared with large-particle aerosol treatment. However, a number of questions remain unanswered about the pragmatic approach relevant for clinicians to consider the role of small airways directed therapy in the day-to-day management of asthma and COPD. We thus have tried to clarify the dilemmas, confusion, and misconceptions related to small airways directed therapy. To this end, we have reviewed all studies on small-particle aerosol therapy systematically to address the dilemmas, confusion, and misconceptions related to small airways directed therapy. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  14. Exercise-Induced Changes in Exhaled NO Differentiates Asthma With or Without Fixed Airway Obstruction From COPD With Dynamic Hyperinflation

    PubMed Central

    Huang, Shu-Yi; Chou, Pai-Chien; Wang, Tsai-Yu; Lo, Yu-Lun; Joa, Wen-Ching; Chen, Li-Fei; Sheng, Te-Fang; Chung, Kian Fan; Wang, Chun-Hua; Kuo, Han-Pin

    2016-01-01

    Abstract Asthmatic patients with fixed airway obstruction (FAO) and patients with chronic obstructive pulmonary disease (COPD) share similarities in terms of irreversible pulmonary function impairment. Exhaled nitric oxide (eNO) has been documented as a marker of airway inflammation in asthma, but not in COPD. To examine whether the basal eNO level and the change after exercise may differentiate asthmatics with FAO from COPD, 27 normal subjects, 60 stable asthmatics, and 62 stable COPD patients were studied. Asthmatics with FAO (n = 29) were defined as showing a postbronchodilator FEV1/forced vital capacity (FVC) ≤70% and FEV1 less than 80% predicted after inhaled salbutamol (400 μg). COPD with dynamic hyperinflation (n = 31) was defined as a decrease in inspiratory capacity (ΔIC%) after a 6 minute walk test (6MWT). Basal levels of eNO were significantly higher in asthmatics and COPD patients compared to normal subjects. The changes in eNO after 6MWT were negatively correlated with the percent change in IC (r = −0.380, n = 29, P = 0.042) in asthmatics with FAO. Their levels of basal eNO correlated with the maximum mid-expiratory flow (MMEF % predicted) before and after 6MWT. In COPD patients with air-trapping, the percent change of eNO was positively correlated to ΔIC% (rs = 0.404, n = 31, P = 0.024). We conclude that asthma with FAO may represent residual inflammation in the airways, while dynamic hyperinflation in COPD may retain NO in the distal airspace. eNO changes after 6MWT may differentiate the subgroups of asthma or COPD patients and will help toward delivery of individualized therapy for airflow obstruction. PMID:27082615

  15. Antileukotriene Reverts the Early Effects of Inflammatory Response of Distal Parenchyma in Experimental Chronic Allergic Inflammation

    PubMed Central

    Gobbato, Nathália Brandão; de Souza, Flávia Castro Ribas; Fumagalli, Stella Bruna Napolitano; Lopes, Fernanda Degobbi Tenório Quirino dos Santos; Prado, Carla Máximo; Martins, Milton Arruda; Tibério, Iolanda de Fátima Lopes Calvo; Leick, Edna Aparecida

    2013-01-01

    Aims. Compare the effects of montelukast or dexamethasone in distal lung parenchyma and airway walls of guinea pigs (GP) with chronic allergic inflammation. Methods. GP have inhaled ovalbumin (OVA group-2x/week/4weeks). After the 4th inhalation, GP were treated with montelukast or dexamethasone. After 72 hours of the 7th inhalation, GP were anesthetised, and lungs were removed and submitted to histopathological evaluation. Results. Montelukast and dexamethasone treatments reduced the number of eosinophils in airway wall and distal lung parenchyma compared to OVA group (P < 0.05). On distal parenchyma, both treatments were effective in reducing RANTES, NF-κB, and fibronectin positive cells compared to OVA group (P < 0.001). Montelukast was more effective in reducing eotaxin positive cells on distal parenchyma compared to dexamethasone treatment (P < 0.001), while there was a more expressive reduction of IGF-I positive cells in OVA-D group (P < 0.001). On airway walls, montelukast and dexamethasone were effective in reducing IGF-I, RANTES, and fibronectin positive cells compared to OVA group (P < 0.05). Dexamethasone was more effective in reducing the number of eotaxin and NF-κB positive cells than Montelukast (P < 0.05). Conclusions. In this animal model, both treatments were effective in modulating allergic inflammation and remodeling distal lung parenchyma and airway wall, contributing to a better control of the inflammatory response. PMID:24151607

  16. Osmotic regulation of airway reactivity by epithelium.

    PubMed

    Fedan, J S; Yuan, L X; Chang, V C; Viola, J O; Cutler, D; Pettit, L L

    1999-05-01

    Inhalation of nonisotonic solutions can elicit pulmonary obstruction in asthmatic airways. We evaluated the hypothesis that the respiratory epithelium is involved in responses of the airways to nonisotonic solutions using the guinea pig isolated, perfused trachea preparation to restrict applied agents to the mucosal (intraluminal) or serosal (extraluminal) surface of the airway. In methacholine-contracted tracheae, intraluminally applied NaCl or KCl equipotently caused relaxation that was unaffected by the cyclo-oxygenase inhibitor, indomethacin, but was attenuated by removal of the epithelium and Na+ and Cl- channel blockers. Na+-K+-2Cl- cotransporter and nitric oxide synthase blockers caused a slight inhibition of relaxation, whereas Na+,K+-pump inhibition produced a small potentiation. Intraluminal hyperosmolar KCl and NaCl inhibited contractions in response to intra- or extraluminally applied methacholine, as well as neurogenic cholinergic contractions elicited with electric field stimulation (+/- indomethacin). Extraluminally applied NaCl and KCl elicited epithelium-dependent relaxation (which for KCl was followed by contraction). In contrast to the effects of hyperosmolarity, intraluminal hypo-osmolarity caused papaverine-inhibitable contractions (+/- epithelium). These findings suggest that the epithelium is an osmotic sensor which, through the release of epithelium-derived relaxing factor, can regulate airway diameter by modulating smooth muscle responsiveness and excitatory neurotransmission.

  17. Cuffed oropharyngeal airway for difficult airway management.

    PubMed

    Takaishi, Kazumi; Kawahito, Shinji; Tomioka, Shigemasa; Eguchi, Satoru; Kitahata, Hiroshi

    2014-01-01

    Difficulties with airway management are often caused by anatomic abnormalities due to previous oral surgery. We performed general anesthesia for a patient who had undergone several operations such as hemisection of the mandible and reconstructive surgery with a deltopectoralis flap, resulting in severe maxillofacial deformation. This made it impossible to ventilate with a face mask and to intubate in the normal way. An attempt at oral awake intubation using fiberoptic bronchoscopy was unsuccessful because of severe anatomical abnormality of the neck. We therefore decided to perform retrograde intubation and selected the cuffed oropharyngeal airway (COPA) for airway management. We inserted the COPA, not through the patient's mouth but through the abnormal oropharyngeal space. Retrograde nasal intubation was accomplished with controlled ventilation through the COPA, which proved to be very useful for this difficult airway management during tracheal intubation even though the method was unusual.

  18. Laparoscopic Distal Pancreatectomy

    PubMed Central

    Melotti, Gianluigi; Butturini, Giovanni; Piccoli, Micaela; Casetti, Luca; Bassi, Claudio; Mullineris, Barbara; Lazzaretti, Maria Grazia; Pederzoli, Paolo

    2007-01-01

    Objective: To describe the clinical characteristics, indications, technical procedures, and outcome of a consecutive series of laparoscopic distal pancreatic resections performed by the same surgical team. Summary Background Data: Laparoscopic distal pancreatic resection has increasingly been described as a feasible and safe procedure, although accompanied by a high rate of conversion and morbidity. Methods: A consecutive series of patients affected by solid and cystic tumors were selected prospectively to undergo laparoscopic distal pancreatectomy performed by the same surgical team. Clinical characteristics as well as diagnostic preoperative assessment and intra- and postoperative data were prospectively recorded. A follow-up of at least 3 months was available for all patients. Results: Fifty-eight patients underwent laparoscopic resection between May 1999 and November 2005. All procedures were successfully performed laparoscopically, and no patient required intraoperative blood transfusion. Splenic vessel preservation was possible in 84.4% of spleen-preserving procedures. There were no mortalities. The overall median hospital stay was 9 days, while it was 10.5 days for patients with postoperative pancreatic fistulae (27.5% of all cases). Follow-up was available for all patients. Conclusions: Our experience in 58 consecutive patients was characterized by the lack of conversions and by acceptable rates of postoperative pancreatic fistulae and morbidity. Laparoscopy proved especially beneficial in patients with postoperative complications as they had a relatively short hospital stay. Solid and cystic tumors of the distal pancreas represent a good indication for laparoscopic resection whenever possible. PMID:17592294

  19. The usefulness of biomarkers of airway inflammation in managing asthma.

    PubMed

    Patil, Sarita U; Long, Aidan A

    2010-01-01

    The goal of managing asthma is to maintain disease control. Current approaches to assessment of control do not include measurement of airway inflammation. This study was designed to assess the usefulness of biomarkers of airway inflammation in guiding asthma management decisions. A literature review was performed. Bronchial biopsy is a direct measure of airway inflammation but not practical for routine use. Enumeration of sputum eosinophils is very useful in guiding changes in controller medication to decrease asthma exacerbations, whereas measurement of exhaled nitric oxide has not proven to be useful in this regard. Serial measurement of airway hyperreactivity as a guide to asthma management yields inconclusive results. Use of indirect stimuli for bronchial challenge offers both practical and theoretical advantages in the assessment of airway hyperreactivity. Data on the analysis of exhaled breath condensate have not yet been studied adequately in guiding management decisions. Enumeration of sputum cell counts appears to be the most useful biomarker of airway inflammation in guiding asthma management decisions. Combined approaches using simple methods of measuring airway hyperreactivity and obtaining sputum samples hold promise for the future, particularly if rapid analysis of cellular products in sputum can be developed.

  20. Computed tomography measurements for airway stent insertion in malignant airway obstruction.

    PubMed

    Righini, Christian; Aniwidyaningsih, Wahju; Ferretti, Gilbert; Pra, Yves; Raymond, Christel Saint; Ferretti, Katharina; Hustache, Claire; Diab, Samia; Reyt, Emile; Pison, Christophe M

    2010-01-01

    Metallic airway stents for malignant airway obstruction are considered safe, yet are not without complications. This study reviews the role of computed tomography (CT) airway measurements for planning stent placement in malignant airway obstruction before the actual therapeutic procedure to avoid invasive diagnostic evaluation before the stent placement and to reduce complications. This study is a retrospective review of information from a stent order database and medical records of patients receiving stents for malignant airway obstruction at a university hospital over a 12-year period. CT scans were used to determine stent diameter by calculating mean diameters of healthy adjacent zones (proximal and distal), stent length (length of diseased airway), and location and number of potential stents. Results of CT planning before bronchoscopy were judged by complication rates. Patient population consisted of 69 patients, 61.7±14.0 years old, 40 males, in whom 92 stents were inserted. The most frequent cause of airway obstructions was tracheobronchial cancer (32). All patients had nitinol stent placement; 66 stents were covered and 26 were uncovered. Follow-up time was 1 to 1067 days (median: 35 days). Complication rate was 10.1% and mainly involved the patients with tracheal obstruction (6). Complications included stent fractures (2), migration (2), granuloma (1), and infectious tracheitis (2). One early death within 24 hours after the procedure was not related to stent placement. Five patients required follow-up therapeutic bronchoscopy to treat the complications. These results suggest that prestent planning by noninvasive method of obtaining CT scan provides optimal stent size and position, possibly avoiding a diagnostic bronchoscopy and reducing complications. Further prospective study is needed to confirm these results because of limitation of this study's design.

  1. [Regeneration of airway epithelium].

    PubMed

    Adam, D; Perotin, J-M; Lebargy, F; Birembaut, P; Deslée, G; Coraux, C

    2014-04-01

    Epithelial regeneration is a complex process. It can lead to the remodeling of the airway epithelium as in asthma, COPD or cystic fibrosis. The development of in vivo and in vitro models has allowed the analysis of remodeling mechanisms and showed the role of components of extracellular matrix, proteases, cytokines and growth factors. Airway epithelial progenitors and stems cells have been studied in these models. However, their identification remains difficult. Identification and characterization of airway epithelial progenitor/stem-cells, and a better knowledge of the regeneration process may allow the development of new therapeutic strategies for airway epithelial reconstitution. Copyright © 2013 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  2. Airway cells after swimming outdoors or in the sea in nonasthmatic athletes.

    PubMed

    Bonsignore, Maria R; Morici, Giuseppe; Riccobono, Loredana; Profita, Mirella; Bonanno, Anna; Paternò, Alessandra; Di Giorgi, Rossana; Chimenti, Laura; Abate, Pietro; Mirabella, Franco; Maurizio Vignola, A; Bonsignore, Giovanni

    2003-07-01

    Marathon runners and elite swimmers showed increased inflammatory cells in the airways at baseline. Although airway neutrophils increase further after a marathon race, the airway response to swimming is unknown. The aim of this study was to assess the effects of swimming on airway cells. To avoid the concomitant effects of chronic exposure to chlorine, the study was conducted in seven nonasthmatic swimmers [mean age (SD): 23.3 +/- 7.7 yr, training: 32 +/- 15 km.wk-1] habitually training in an outdoor pool (OP), i.e., a low-chlorine environment. Spirometry, exhaled nitric oxide (NO), induced sputum, and peripheral blood samples were obtained at baseline, after a 5-km trial in OP, and after a 5-km race in the sea (S), i.e., hypertonic airway exposure. Airway neutrophil differential counts at baseline were higher in swimmers than in sedentary controls (N = 10), but cell counts, neutrophil elastase, and eosinophil cationic protein were unaffected by 5-km swimming. After swimming, L-selectin expression on airway cells decreased, suggesting exercise-induced cell mobilization into the airways and/or direct effects of hyperventilation on airway cells. After S, airway eosinophil differential counts increased slightly. Exhaled NO concentration was 19 +/- 6 ppb at baseline, 8 +/- 4 ppb after OP, and 21 +/- 7 ppb after S (P < 0.005 for OP vs baseline and S). In swimmers not chronically exposed to high chlorine concentrations, data obtained at baseline suggest a direct relationship between airway neutrophilia and endurance training. The low L-selectin expression by airway cells postexercise suggests hyperventilation-induced cell recruitment or modulation of cell function. Hypertonic exposure of airways during exercise may slightly increase airway eosinophils and exhaled NO. Overall, 5-km swimming exerted smaller effects on airway cells than running a marathon.

  3. [Nitric oxide in the nose and paranasal sinuses--respiratory tract physiology in a new perspective].

    PubMed

    Djupesland, P G; Chatkin, J M; Qian, W; Haight, J S

    1999-11-10

    Nitric oxide (NO) has important functions in a variety of physiological and pathophysiological processes in the body, including vasoregulation, haemostasis, neurotransmission, immunity and respiration. The discovery of surprisingly high concentrations of NO in the nasal airway and paranasal sinuses has important implications for the understanding of airway physiology. The high NO levels in the nasal and paranasal airways contribute to the first line defence against microorganisms. Furthermore, autoinhalation of nasal NO may improve pulmonary function and other remote physiological processes. This airborne messenger system represents a new physiological concept of potential clinical importance. However, NO, like several other mediators, has a dualistic function. Airway NO levels are increased in airway inflammations, such as asthma and allergic rhinitis, but is reduced in cystic fibrosis and other conditions with ciliary dysfunction, sinusitis and after exposure to tobacco and alcohol. Consequently, NO may prove valuable as a non-invasive marker in the diagnosis and monitoring of airway pathologies.

  4. [Pulmonary metabolism of nitric oxide (NO) in patients with cystic fibrosis].

    PubMed

    Grasemann, H; Ratjen, F

    2002-06-01

    Airway nitric oxide (NO) and its metabolites are involved in a number of physiological and pathophysiological processes. For instance, NO relaxes airway smooth muscle, improves airway ciliary motility, has antimicrobial effects, and increases expression of the CFTR (cystic fibrosis transmembrane regulator) protein in airway epithelial cells. Of interest, concentrations of NO and of bioactive S-nitrosothiols (SNOs) are decreased in the airways of patients with cystic fibrosis (CF). When compared to patients with relatively normal pulmonary NO formation, CF patients with low NO-concentrations have a significantly reduced pulmonary function and a higher frequency of bacterial colonisation of the airways with pathogens such as P. aeruginosa. As a consequence of these observations clinical trails have now been initiated to study possible effects of an augmented bronchial NO-concentration in CF-patients.

  5. Distal Radioulnar Joint Instability

    PubMed Central

    Mirghasemi, Ali R.; Lee, Daniel J.; Rahimi, Narges; Rashidinia, Shervin

    2015-01-01

    Distal radioulnar joint (DRUJ) instability is a common clinical condition but a frequently missed diagnosis. Both surgical and nonsurgical treatments are possible for chronic cases of DRUJ instability. Nonsurgical treatment can be considered as the primary therapy in less active patients, while surgery should be considered to recover bone and ligament injuries if nonsurgical treatment fails to restore forearm stability and function. The appropriate choice of treatment depends on the individual patient and specific derangement of the DRUJ PMID:26328241

  6. Distal radioulnar joint injuries

    PubMed Central

    Thomas, Binu P; Sreekanth, Raveendran

    2012-01-01

    Distal radioulnar joint is a trochoid joint relatively new in evolution. Along with proximal radioulnar joint, forearm bones and interosseous membrane, it allows pronosupination and load transmission across the wrist. Injuries around distal radioulnar joint are not uncommon, and are usually associated with distal radius fractures,fractures of the ulnar styloid and with the eponymous Galeazzi or Essex_Lopresti fractures. The injury can be purely involving the soft tissue especially the triangular fibrocartilage or the radioulnar ligaments. The patients usually present with ulnar sided wrist pain, features of instability, or restriction of rotation. Difficulty in carrying loads in the hand is a major constraint for these patients. Thorough clinical examination to localize point of tenderness and appropriate provocative tests help in diagnosis. Radiology and MRI are extremely useful, while arthroscopy is the gold standard for evaluation. The treatment protocols are continuously evolving and range from conservative, arthroscopic to open surgical methods. Isolated dislocation are uncommon. Basal fractures of the ulnar styloid tend to make the joint unstable and may require operative intervention. Chronic instability requires reconstruction of the stabilizing ligaments to avoid onset of arthritis. Prosthetic replacement in arthritis is gaining acceptance in the management of arthritis. PMID:23162140

  7. The effects of inhaled corticosteroids on intrinsic responsiveness and histology of airways from infant monkeys exposed to house dust mite allergen and ozone

    SciTech Connect

    Joad, Jesse P. Kott, Kayleen S.; Bric, John M.; Schelegle, Edward S.; Gershwin, Laurel J.; Plopper, Charles G.; Peake, Janice L.; Pinkerton, Kent E.

    2008-01-15

    Inhaled corticosteroids (ICS) are recommended to treat infants with asthma, some with intermittent asthma. We previously showed that exposing infant monkeys to allergen/ozone resulted in asthma-like characteristics of their airways. We evaluated the effects of ICS on histology and intrinsic responsiveness of allergen/ozone-exposed and normal infant primate airways. Infant monkeys were exposed by inhalation to (1) filtered air and saline, (2) house dust mite allergen (HDMA) + ozone and saline, (3) filtered air and ICS (budesonide) or (4) HDMA + ozone and ICS. Allergen/ozone exposures started at 1 month and ICS at 3 months of age. At 6 months of age, methacholine-induced changes in luminal area of airways in proximal and distal lung slices were determined using videomicrometry, followed by histology of the same slices. Proximal airway responsiveness was increased by allergen/ozone and by ICS. Eosinophil profiles were increased by allergen/ozone in both proximal and distal airways, an effect that was decreased by ICS in distal airways. In both allergen/ozone- and air-exposed monkeys, ICS increased the number of alveolar attachments in distal airways, decreased mucin in proximal airways and decreased epithelial volume in both airways. ICS increased smooth muscle in air-exposed animals while decreasing it in allergen/ozone-exposed animals in both airways. In proximal airways, there was a small but significant positive correlation between smooth muscle and airway responsiveness, as well as between alveolar attachments and responsiveness. ICS change morphology and function in normal airways as well as allergen/ozone-exposed airways, suggesting that they should be reserved for infants with active symptoms.

  8. Small airway asthma therapy, challenges, and the future.

    PubMed

    Casale, Thomas B

    2003-02-01

    The clinical significance of small airway pathology makes these passages an important therapeutic target in asthma. Conventional chlorofluorocarbon-based formulations of inhaled corticosteroids for asthmatic inflammation produce aerosols with a relatively large particle size, and as such, offer poor access to the small airways. New corticosteroid formulations use hydrofluoroalkane propellants with a smaller average particle size, allowing better access to the distal lung. By extending the delivery of this medication to the peripheral lung and by increasing the efficiency of lung targeting, these new corticosteroid formulations provide more effective treatment at reduced drug doses.

  9. The laryngeal mask airway.

    PubMed

    Brimacombe, J; Shorney, N

    The laryngeal mask airway is a new development in airway management. It became commercially available in 1988 and has since become an integral part of anaesthetic practice; its potential outside anaesthesia is rapidly developing. This article describes the basic concepts, methods of insertion and applications, current and projected.

  10. Controversies in Pediatric Perioperative Airways.

    PubMed

    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.

  11. 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

  12. CT-assessed large airway involvement and lung function decline in eosinophilic asthma: The association between induced sputum eosinophil differential counts and airway remodeling.

    PubMed

    Inoue, Hideki; Ito, Isao; Niimi, Akio; Matsumoto, Hisako; Matsuoka, Hirofumi; Jinnai, Makiko; Takeda, Tomoshi; Oguma, Tsuyoshi; Otsuka, Kojiro; Nakaji, Hitoshi; Tajiri, Tomoko; Iwata, Toshiyuki; Nagasaki, Tadao; Kanemitsu, Yoshihiro; Mishima, Michiaki

    2016-11-01

    Eosinophilic asthma (EA) is a distinct clinical phenotype characterized by eosinophilic airway inflammation and airway remodeling. Few studies have used computed tomography (CT) scanning to assess the association between sputum eosinophil differential counts and airway involvement. We aimed to investigate the clinical characteristics and airway involvement of EA, and to examine the correlation between induced sputum eosinophil differential counts and CT-assessed airway remodeling. We retrospectively divided 63 patients with stable asthma receiving inhaled corticosteroids into 2 groups: 26 patients with EA (sputum eosinophil >3%) and 37 patients with non-eosinophilic asthma (NEA). Clinical measurements such as spirometry, fractional exhaled nitric oxide levels (FeNO), and CT-assessed indices of airway involvement were compared between the groups. Multivariate analysis was performed to identify determinants of the percentage of wall area (WA%). The EA group had significantly longer asthma duration, lower pulmonary function, and higher FeNO than the NEA group. Also, the EA group had higher WA% and smaller airway luminal area than the NEA group. Sputum eosinophil differential counts and WA% were positively correlated. The multivariate linear regression analysis showed that the factors associated with WA% included sputum eosinophil differential counts, age, and body mass index. However, asthma duration was not associated with WA%. Our CT-assessed findings demonstrated large airway involvement in EA, and we observed a positive association between induced sputum eosinophil differential counts and WA%. The findings indicate that induced sputum eosinophil differential counts may be associated with airway remodeling in patients with stable asthma.

  13. Chibby promotes ciliary vesicle formation and basal body docking during airway cell differentiation.

    PubMed

    Burke, Michael C; Li, Feng-Qian; Cyge, Benjamin; Arashiro, Takeshi; Brechbuhl, Heather M; Chen, Xingwang; Siller, Saul S; Weiss, Matthew A; O'Connell, Christopher B; Love, Damon; Westlake, Christopher J; Reynolds, Susan D; Kuriyama, Ryoko; Takemaru, Ken-Ichi

    2014-10-13

    Airway multiciliated epithelial cells play crucial roles in the mucosal defense system, but their differentiation process remains poorly understood. Mice lacking the basal body component Chibby (Cby) exhibit impaired mucociliary transport caused by defective ciliogenesis, resulting in chronic airway infection. In this paper, using primary cultures of mouse tracheal epithelial cells, we show that Cby facilitates basal body docking to the apical cell membrane through proper formation of ciliary vesicles at the distal appendage during the early stages of ciliogenesis. Cby is recruited to the distal appendages of centrioles via physical interaction with the distal appendage protein CEP164. Cby then associates with the membrane trafficking machinery component Rabin8, a guanine nucleotide exchange factor for the small guanosine triphosphatase Rab8, to promote recruitment of Rab8 and efficient assembly of ciliary vesicles. Thus, our study identifies Cby as a key regulator of ciliary vesicle formation and basal body docking during the differentiation of airway ciliated cells.

  14. L-arginine supplementation and experimental airway hyperreactivity.

    PubMed

    Antosova, M; Strapkova, A

    2013-01-01

    The interest in L-arginine metabolism was triggered primarily by the discovery of nitric oxide (NO) synthesis in mammals and its remarkable biological roles. The real role of L-arginine in the airway hyperreactivity (AHR) has not been established yet. Therefore, we studied whether supplementation of L-arginine can influence the experimental AHR evoked by two different triggers - allergen and exogenous irritant (toluene vapours). Male TRIK strain guinea pigs were used in the study. We used two patterns of pretreatment with L-arginine in vivo, short- and long-term, in a dose of 300 mg/kg administered i.p., after which we studied reactivity of airway smooth muscles in vitro. Pretreatment with L-arginine for 3 days decreased the airway smooth muscle reactivity induced by toluene vapour, whereas pretreatment for 17 days was without any additional effect on smooth muscle reactivity. The short-term pretreatment in ovalbumin-induced hyperreactivity caused an increase in airway smooth muscle reactivity to lower concentrations of both bronchoconstrictors. On the other side, this pretreatment significantly decreased smooth muscle reactivity to high concentrations of both bronchoconstrictors. Supplementation of L-arginine resulted in a modification of the airway smooth muscle response. The effect of supplementation was different depending on the AHR trigger, airway region and pretreatment duration. The results also underscore the importance of an optimal L-arginine level for the control of bronchial tone.

  15. Distal tibiofibular radiological overlap

    PubMed Central

    Sowman, B.; Radic, R.; Kuster, M.; Yates, P.; Breidiel, B.; Karamfilef, S.

    2012-01-01

    Objectives Overlap between the distal tibia and fibula has always been quoted to be positive. If the value is not positive then an injury to the syndesmosis is thought to exist. Our null hypothesis is that it is a normal variant in the adult population. Methods We looked at axial CT scans of the ankle in 325 patients for the presence of overlap between the distal tibia and fibula. Where we thought this was possible we reconstructed the images to represent a plain film radiograph which we were able to rotate and view in multiple planes to confirm the assessment. Results The scans were taken for reasons other than pathology of the ankle. We found there was no overlap in four patients. These patients were then questioned about previous injury, trauma, surgery or pain, in order to exclude underlying pathology. Conclusion We concluded that no overlap between the tibia and fibula may exist in the population, albeit in a very small proportion. PMID:23610666

  16. Open Reduction, Internal Fixation Distal Intraarticular Distal Humerus Fracture.

    PubMed

    Fuller, David A

    2016-08-01

    The purpose of this video is to demonstrate the surgical repair of an intraarticular distal humerus fracture. A polytrauma patient with an intraarticular distal humerus fracture is shown. The patient is positioned laterally, with a posterior skin incision and olecranon osteotomy for exposure. An anatomic reduction is achieved, and internal fixation with perpendicular plating of the distal humerus is performed. The video is 18 minutes, 34 seconds duration in time and 2,048,752,000 bytes in size. Open reduction with internal fixation of a distal humerus fracture is demonstrated in this video.

  17. Small airways involvement in coal mine dust lung disease.

    PubMed

    Long, Joshua; Stansbury, Robert C; Petsonk, Edward L

    2015-06-01

    Inhalation of coal mine dust results in a spectrum of symptoms, dysfunction, and pathological changes in the respiratory tract that collectively have been labeled coal mine dust lung disease. Recent reports from periodic health surveillance among underground and surface coal miners in the United States have demonstrated an increasing prevalence and severity of dust diseases, and have also documented that some miners experience rapid disease progression. The coal macule is an inflammatory lesion associated with deposited dust, and occurs in the region of the most distal conducting airways and proximal respiratory bronchioles. Inflammatory changes in the small airways have long been recognized as the signature lung pathology among coal miners. Human and laboratory studies have suggested oxidant injury, and increased recruitment and activity of macrophages play important roles in dust-induced lung injury. However, the functional importance of the small airway changes was debated for many years. We reviewed published literature that documents a pervasive occurrence of both physiologic and structural abnormalities in small airways among coal miners and other workers exposed to airborne particulates. There is increasing evidence supporting an important association of abnormalities in the small peripheral airways with the development of respiratory symptoms, deficits in spirometry values, and accelerated declines in ventilatory lung function. Pathologic changes associated with mineral dust deposition in the small airways may be of particular importance in contemporary miners with rapidly progressive respiratory impairment.

  18. Airway Monitoring experiment

    NASA Image and Video Library

    2016-02-25

    ISS046e048360 (02/25/2016) --- NASA astronaut Tim Kopra prepares to participate in the Airway Monitoring experiment. With dust particles present in the International Space Station atmosphere, Airway Monitoring studies the occurrence and indicators of airway inflammation in crewmembers, using ultra-sensitive gas analyzers to analyze exhaled air. This helps to highlight any health impacts and to maintain crewmember well-being on future human spaceflight missions, especially longer-duration missions to the Moon and Mars for example, where crewmembers will have to be more self-sufficient in highlighting and avoiding such conditions.

  19. Airway Monitoring experiment

    NASA Image and Video Library

    2016-02-25

    ISS046e047972 (02/25/2016) --- ESA (European Space Agency) astronaut Timothy Peake participates in the Airway Monitoring experiment. With dust particles present in the International Space Station atmosphere, Airway Monitoring studies the occurrence and indicators of airway inflammation in crewmembers, using ultra-sensitive gas analyzers to analyze exhaled air. This helps to highlight any health impacts and to maintain crewmember well-being on future human spaceflight missions, especially longer-duration missions to the Moon and Mars for example, where crewmembers will have to be more self-sufficient in highlighting and avoiding such conditions.

  20. Exhaled nitric oxide measurement in patients affected by nasal polyposis.

    PubMed

    Galli, Jacopo; Montuschi, Paolo; Passàli, Giulio Cesare; Laruffa, Marianna; Parrilla, Claudio; Paludetti, Gaetano

    2012-08-01

    Nitric oxide (NO) is produced in the respiratory tract with a major contribution coming from paranasal sinuses and the nose. The pathophysiological role of NO in the airways has been debated. The aims of this study were to measure fraction of exhaled NO (FENO), a validated marker of airway inflammation, in patients affected by nasal polyposis with and without asthma; to assess the importance of FENO measurement in detecting subclinical involvement of lower airways in patients with clinical rhinosinusal symptoms; and to clarify the impact of endoscopic surgical removal of polyps on airway inflammation. The study was conducted at the O.R.L. Clinic and Clinical Pharmacology Unit, University Hospital Agostino Gemelli, Rome, Italy. Prospective study. Concentrations of FENO were measured with the NIOX system (Aerocrine, Stockholm, Sweden) by using a single-breath online method, according to the American Thoracic Society guidelines. Compared with those in healthy subjects (15 [11-19] ppb, n = 15; P < .0001), FENO values were elevated in patients with nasal polyposis (41 [21-77] ppb, n = 43). There was no significant difference in FENO concentrations between asthmatic and nonasthmatic patients with nasal polyposis (P = .73). Concentrations of FENO in patients with nasal polyposis were decreased after surgery (64.2 [30.0-132.7] ppb vs 56.0 [26.4-73.8] ppb, respectively; P = .03). The fraction of exhaled NO is elevated in the inflammatory process involving both the rhinosinusal district and lower airways, supporting the one-airway disease hypothesis.

  1. Airway hyperresponsiveness in asthma: mechanisms, clinical significance, and treatment.

    PubMed

    Brannan, John D; Lougheed, M Diane

    2012-01-01

    Airway hyperresponsiveness (AHR) and airway inflammation are key pathophysiological features of asthma. Bronchial provocation tests (BPTs) are objective tests for AHR that are clinically useful to aid in the diagnosis of asthma in both adults and children. BPTs can be either "direct" or "indirect," referring to the mechanism by which a stimulus mediates bronchoconstriction. Direct BPTs refer to the administration of pharmacological agonist (e.g., methacholine or histamine) that act on specific receptors on the airway smooth muscle. Airway inflammation and/or airway remodeling may be key determinants of the response to direct stimuli. Indirect BPTs are those in which the stimulus causes the release of mediators of bronchoconstriction from inflammatory cells (e.g., exercise, allergen, mannitol). Airway sensitivity to indirect stimuli is dependent upon the presence of inflammation (e.g., mast cells, eosinophils), which responds to treatment with inhaled corticosteroids (ICS). Thus, there is a stronger relationship between indices of steroid-sensitive inflammation (e.g., sputum eosinophils, fraction of exhaled nitric oxide) and airway sensitivity to indirect compared to direct stimuli. Regular treatment with ICS does not result in the complete inhibition of responsiveness to direct stimuli. AHR to indirect stimuli identifies individuals that are highly likely to have a clinical improvement with ICS therapy in association with an inhibition of airway sensitivity following weeks to months of treatment with ICS. To comprehend the clinical utility of direct or indirect stimuli in either diagnosis of asthma or monitoring of therapeutic intervention requires an understanding of the underlying pathophysiology of AHR and mechanisms of action of both stimuli.

  2. Airway remodeling and inflammation in competitive swimmers training in indoor chlorinated swimming pools.

    PubMed

    Bougault, Valérie; Loubaki, Lionel; Joubert, Philippe; Turmel, Julie; Couture, Christian; Laviolette, Michel; Chakir, Jamila; Boulet, Louis-Philippe

    2012-02-01

    Airway disorders are common in regular chlorinated swimming pool attendees, particularly competitive athletes, but the impact of intense swimming training on airway function and structure remains unclear. This study aimed to evaluate airway inflammation and remodeling in elite swimmers. Twenty-three elite swimmers were tested during off-training season. All had exhaled nitric oxide measurement, methacholine test, eucapnic voluntary hyperpnea challenge, allergy skin prick tests, and bronchoscopy with bronchial biopsies. Clinical data and tissues from 10 age-matched mild-asthmatic and 10 healthy nonallergic subjects were used for comparison. Swimmers had increased airway mucosa eosinophil and mast cell counts than did controls (P < .05). They had more goblet cell hyperplasia and higher mucin expression than did healthy or asthmatic subjects (P < .05). A greater submucosal type I and III collagen expression and tenascin deposition was also observed in swimmers than in controls (P < .05). Neither exhaled nitric oxide nor airway responsiveness to methacholine or eucapnic voluntary hyperpnea challenge correlated with these inflammatory and remodeling changes. Intense, long-term swimming training in indoor chlorinated swimming pools is associated with airway changes similar to those seen in mild asthma, but with higher mucin expression. These changes were independent from airway hyperresponsiveness. The long-term physiological and clinical consequences of these changes remain to be clarified. Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  3. Emergency airway puncture

    MedlinePlus

    ... be inserted into the throat, just below the Adam's apple (cricoid cartilage), into the airway. In a ... commercial use must be authorized in writing by ADAM Health Solutions. About MedlinePlus Site Map FAQs Customer ...

  4. Distal arthrogryposis syndrome

    PubMed Central

    Kulkarni, K. P.; Panigrahi, I.; Ray, M.; Marwaha, R. K.

    2008-01-01

    A 5-month-old male infant presented with weak cry, decreased body movements, tightness of whole body since birth, and one episode of generalized seizure on day 4 of life. He was born at term by elective caesarian section performed for breech presentation. The child had failure to thrive, contractures at elbow and knee joints, hypertonia, microcephaly, small mouth, retrognathia, and camptodactyly. There was global developmental delay. Abdominal examination revealed umbilical and bilateral inguinal hernia. Visual evoked response and brainstem evoked response audiometry were abnormal. Nerve conduction velocity was normal. Magnetic resonance imaging of brain revealed paucity of white matter in bilateral cerebral hemispheres with cerebellar and brain stem atrophy. The differential diagnoses considered in the index patient were distal arthrogryposis (DA) syndrome, cerebroculofacioskeletal syndrome, and Pena Shokier syndrome. The index patient most likely represents a variant of DA: Sheldon Hall syndrome. PMID:20300297

  5. [Chest physical therapy of the distal lung. Mechanical basis of a new paradigm].

    PubMed

    Postiaux, G

    2014-06-01

    Recent medical literature has shown that there has been renewed interest focused on the small airways deep in the lung tissue. Although there is involvement of the distal airways at an early stage in mucus secreting lung diseases, no specific chest physical therapy (CPT) manoeuver has been proposed for small airways clearance. A four-tier classification of CPT has been established with identification of its benefits at each level of a monoalveolar respiratory tract model. The usual expiratory techniques directed towards the upper and middle respiratory tract are not applicable to the small airways and new paradigm is proposed appropriate to their specific mechanical characteristics. This comprises a slow resistive inspiratory manoeuver in the lateral position. Clinical auscultation of the lung is the cornerstone of the validation and follow-up of the technique. Copyright © 2014 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  6. Ventilation catheter-assisted airway stenting under local anaesthesia for patients with airway stenosis: initial clinical experience.

    PubMed

    Wei, Ning; Fu, Yu-Fei; Zhang, Ke; Wan, Hao-Guang; Xu, Hao

    2015-04-01

    This report details our preliminary results of ventilation catheter-assisted airway stenting under local anaesthesia for airway stenosis. Fifteen consecutive patients with airway stenosis underwent ventilation catheter-assisted airway stenting under local anaesthesia. A 4F angiographic catheter was used as the ventilation catheter. During the treatment, the distal tip of the ventilation catheter was placed across the stenosis into one of the main bronchi and the proximal tip of the catheter was linked to the oxygen tube for oxygen supplementation. Airway stenting was performed under ventilation support. Patients maintained autonomous respiration throughout the procedures. Data on technical success, clinical outcome and follow-up were collected and analysed. Ventilation catheter-assisted airway stenting under local anaesthesia was technically successful and well tolerated in all patients. Respiratory difficulty was improved in all patients after treatment. The average Hugh-Jones classification grade, arterial oxygen saturation value, and respiratory rate improved from 4.20 ± 0.68, 80.60 ± 3.83%, and 30.33 ± 2.02 times/min, respectively, before stenting to 1.47 ± 0.52 (P < 0.001), 94.93 ± 1.33% (P < 0.001), and 18.07 ± 1.33 times/min (P < 0.001), respectively, after stenting. After 2-11 months (average 5.73 ± 2.40 months) of follow-up, one patient experienced re-stenosis of the stent. The mean survival time of the 15 patients was 162.00 ± 71.60 days (range 55-320 days). Ventilation catheter-assisted airway stenting under local anaesthesia can be an effective, simple and safe method for airway stenosis.

  7. Interspecies comparisons of particle deposition and mucociliary clearance in tracheobronchial airways

    SciTech Connect

    Lippmann, M.; Schlesinger, R.B.

    1984-01-01

    Inhaled insoluble particles that deposit along normal healthy tracheobronchial airways of humans and other mammals are transported on the proximally moving mucous lining to the larynx, where they are swallowed. The transit time from the most distal ciliated airways varies from 0.1 to 1 d, with each individual having a relatively constant, characteristic time. The exact time course of clearance depends on the distributions of both particle deposition and mucus velocities along the airways. As compared to commonly used experimental animals, humans have larger lungs and a more symmetric upper bronchial airway branching pattern. In addition, humans do considerable oral breathing, thus bypassing the effective air cleaning capability of the nasal airways. These differences contribute to a greater amount of upper bronchial airway particle deposition in humans, as well as to greater concentrations of deposition on localized surfaces near airway bifurcations. Airborne irritants that deposit in small ciliated airways may produce marked changes in mucociliary transport. Such materials include cigarette smoke, submicrometer-sized sulfuric acid mist, nitrogen dioxide, and ozone. For cigarette smoke and sulfuric acid, which have been studied for transient effects following single brief exposures in animals, both of these irritants produce persistant alterations in clearance rates and airway morphometry. Studies of the effects of ozone on mucociliary clearance have, up to now, been limited to tests of the responses of rats to single exposures. The similarities between the known effects of various irritants suggests a nonspecific response.

  8. Airway stents in children.

    PubMed

    Nicolai, T

    2008-04-01

    Airway obstruction in children is a rare, but difficult clinical problem, with no clear agreement on optimal therapeutic approach. Stenting of the airway has been used successfully in adults, and is an attractive alternative in children. Fundamental differences of pediatric compared to adult use include the benign nature of most stenoses, the narrow and soft airways of children, the required long-term tolerance and adaptation to growth. These differences may significantly alter the therapeutic balance, calling into question the precise role stents play in the treatment of airway obstruction in children. Stent placement can be technically demanding but is not exceedingly difficult. Experience is necessary to select the proper size and type of stent. Metal stents usually achieve airway patency and clinical improvement in the majority of cases, while this is less frequently the case with silicone stents. Some complications such as granulation and secretion retention seem to occur in most children after stent implantation. Unfortunately, severe complications including death have been reported in a significant proportion of children. Stent related mortality can be estimated at 12.9% from published data, but these include complication centered reports. The initial euphoria for airway stents in children has largely abated and most authors agree that they should only be employed in circumstances with no good alternatives. It is crucial that all surgical and medical alternatives are considered and the decision to place a stent is not made because other options are overlooked or not available locally. Stent use in a palliative setting has also been reported and is probably reasonable. Stents will only allow limited adaptation for the growth of pediatric airways by balloon dilatation. All metal stents should be considered as potentially permanent, and removal sometimes may only be possible through a surgical and sometimes risky approach.

  9. Essentials of airway management, oxygenation, and ventilation: part 2: advanced airway devices: supraglottic airways.

    PubMed

    Rosenberg, M B; Phero, J C; Becker, D E

    2014-01-01

    Offices and outpatient dental facilities must be properly equipped with devices for airway management, oxygenation, and ventilation. Part 1 in this series on emergency airway management focused on basic and fundamental considerations for supplying supplemental oxygen to the spontaneously breathing patient and utilizing a bag-valve-mask system including nasopharyngeal and oropharyngeal airways to deliver oxygen under positive pressure to the apneic patient. This article will review the evolution and use of advanced airway devices, specifically supraglottic airways, with the emphasis on the laryngeal mask airway, as the next intervention in difficult airway and ventilation management. The final part of the series (part 3) will address airway evaluation, equipment and devices for tracheal intubation, and invasive airway procedures.

  10. Essentials of Airway Management, Oxygenation, and Ventilation: Part 2: Advanced Airway Devices: Supraglottic Airways

    PubMed Central

    Rosenberg, M. B; Phero, J. C; Becker, D. E

    2014-01-01

    Offices and outpatient dental facilities must be properly equipped with devices for airway management, oxygenation, and ventilation. Part 1 in this series on emergency airway management focused on basic and fundamental considerations for supplying supplemental oxygen to the spontaneously breathing patient and utilizing a bag-valve-mask system including nasopharyngeal and oropharyngeal airways to deliver oxygen under positive pressure to the apneic patient. This article will review the evolution and use of advanced airway devices, specifically supraglottic airways, with the emphasis on the laryngeal mask airway, as the next intervention in difficult airway and ventilation management. The final part of the series (part 3) will address airway evaluation, equipment and devices for tracheal intubation, and invasive airway procedures. PMID:25191986

  11. Distal corporoplasty for distal cylinders extrusion after penile prosthesis implantation.

    PubMed

    Carrino, Maurizio; Chiancone, Francesco; Battaglia, Gaetano; Pucci, Luigi; Fedelini, Paolo

    2017-02-03

    Distal extrusion of cylinders is a potential complication of the penile prosthesis implantation. Several methods have been proposed for repairing a distal penile erosion. We present our preliminary experience in "Distal corporoplasty" technique. We enrolled 18 consecutive patients whose underwent a distal corporoplasty with simultaneous reimplantation of an "AMS 700 inflatable penile prosthesis (LGX)" from January 2013 to November 2015 at our hospital. All procedures were performed by a single surgical team. Intraoperative and postoperative complications have been classified and reported according to Satava6 and Clavien-Dindo (CD) system.7 Mean values with standard deviations (±SD) were computed and reported for all items. Mean age of the patients was 53.61 (±11.90) years. Mean body max index (BMI) was 24.22 (±2.51). Mean operative time was 85.2 (±13.1) minutes. Blood losses were minimal. No intraoperative complications are reported according to Satava classification. Four out of 18 patients (22.22%) experienced postoperative complications according to CD system. All patients had sexual intercourse for the first time postsurgery after a mean of 59.11 ± 2.08 days. Mean follow-up was 22.11 (±9.95). Distal extrusion of cylinders is a potential complication of the penile prosthesis implantation. Distal corporoplasty was first described by Mulcahy. He reported a series of 14 patients with a follow-up of about 2 years with optimal functional outcomes. Moreover, distal corporoplasty resulted in shorter operative time, better function, less pain, and fewer recurrences than Gortex windsock repair.10 In our experience, distal corporoplasty is a simple and safe procedure in the treatment of distal cylinders extrusion when the prosthetic material is not exposed to the exterior.

  12. [Measuring airway inflammation in clinical practise - application and interpretation].

    PubMed

    Holz, O; Buhl, R; Hausen, T; von Berg, A; Weber, M; Worth, H; Magnussen, H

    2007-03-01

    Airway inflammation plays a major role in the pathology of both asthma and COPD and is the target of corticosteroid treatment. In daily routine practise, however, airway inflammation is still not often considered by pneumologists to support the diagnostic process or to aid in disease management, despite studies showing that patients could benefit. Eosinophilic airway inflammation is of special interest, as it is not restricted to allergen-induced airway diseases, and because it generally responds well to anti-inflammatory treatment with corticosteroids. Therefore, the early detection of this kind of underlying inflammatory process can have a positive impact on finding a diagnosis as well as for disease management. The non-invasive detection of eosinophilic airway inflammation using induced sputum is too time consuming and therefore too expensive in outpatient settings. As sputum eosinophils correlate with the concentration of exhaled nitric oxide (FeNO), its measurement could serve as a more economic alternative, especially as new small handheld analysers are available now, that allow the rapid FeNO analysis, even in children. This review will cover some basics and technical aspects of FeNO measurements, which should be known to correctly interprete results in clinical practise. In the second part, the clinical value and the limits of FeNO measurements, as well as the potential interpretation of results are discussed based on recently published literature.

  13. Distinct clinical phenotypes of airways disease defined by cluster analysis.

    PubMed

    Weatherall, M; Travers, J; Shirtcliffe, P M; Marsh, S E; Williams, M V; Nowitz, M R; Aldington, S; Beasley, R

    2009-10-01

    Airways disease is currently classified using diagnostic labels such as asthma, chronic bronchitis and emphysema. The current definitions of these classifications may not reflect the phenotypes of airways disease in the community, which may have differing disease processes, clinical features or responses to treatment. The aim of the present study was to use cluster analysis to explore clinical phenotypes in a community population with airways disease. A random population sample of 25-75-yr-old adults underwent detailed investigation, including a clinical questionnaire, pulmonary function tests, nitric oxide measurements, blood tests and chest computed tomography. Cluster analysis was performed on the subgroup with current respiratory symptoms or obstructive spirometric results. Subjects with a complete dataset (n = 175) were included in the cluster analysis. Five clusters were identified with the following characteristics: cluster 1: severe and markedly variable airflow obstruction with features of atopic asthma, chronic bronchitis and emphysema; cluster 2: features of emphysema alone; cluster 3: atopic asthma with eosinophilic airways inflammation; cluster 4: mild airflow obstruction without other dominant phenotypic features; and cluster 5: chronic bronchitis in nonsmokers. Five distinct clinical phenotypes of airflow obstruction were identified. If confirmed in other populations, these findings may form the basis of a modified taxonomy for the disorders of airways obstruction.

  14. Difficult airway management.

    PubMed

    Rosen, Peter; Sloane, Christian; Ban, Kevin M; Lanigra, Michele; Wolfe, Richard

    2006-01-01

    Airway management is unequivocally the most important responsibility of the emergency physician. No matter how prepared for the task, no matter what technologies are utilized, there will be cases that are difficult. The most important part of success in the management of a difficult airway is preparation. When the patient is encountered, it is too late to check whether appropriate equipment is available, whether a rescue plan has been in place, and what alternative strategies are available for an immediate response. The following article will review the principles of airway management with an emphasis upon preparation, strategies for preventing or avoiding difficulties, and recommended technical details that hopefully will encourage the reader to be more prepared and technically skillful in practice.

  15. Small airway impairment in moderate to severe asthmatics without significant proximal airway obstruction.

    PubMed

    Perez, Thierry; Chanez, Pascal; Dusser, Daniel; Devillier, Philippe

    2013-11-01

    Asthma is a disease characterized by inflammation which affects both proximal and distal airways. We evaluated the prevalence of small airway obstruction (SAO) in a group of clinically stable asthmatics with both normal forced expiratory volume in the first second (FEV1) and normal FEV1/forced vital capacity (FVC) and treated with an association of inhaled corticosteroids (ICSs) and long acting β2-agonists (LABAs). Clinical evaluation included the measurement of dyspnea, asthma control test and drug compliance. The prevalence of SAO was estimated by spirometry and plethysmography and defined by the presence of one or more of the following criteria: functional residual capacity (FRC) > 120% predicted (pred), residual volume (RV) > pred + 1.64 residual standard deviation (RSD), RV/total lung capacity (TLC) > pred + 1.64 RSD, forced expiratory flow (FEF)25-75% < pred - 1.64 RSD, FEF50% < pred - 1.64 RSD, slow vital capacity (SVC) - FVC > 10%. Among the 441 patients who were included, 222 had normal FEV1 and FEV1/FVC. At least one criteria of SAO was found in 115 (52%) mainly lung hyperinflation (39% based on high FRC, RV or RV/TLC) and more rarely distal airflow limitation (15% based on FEF25-75% or FEF50%) or expiratory trapping (10% based on increased SVC - FVC). In the patients with only SAO (no PAO), there was no relationship between SAO, asthma history and the scores of dyspnea, asthma control or drug compliance. These results suggest that in asthmatics with normal FEV1 and FEV1/FVC, treated with ICSs and LABAs, SAO is found in more than half of the patients indicating that the routinely used lung function tests can underestimate dysfunctions occurring in the small airways.

  16. Advances in prehospital airway management.

    PubMed

    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.

  17. 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

  18. Asthma, atopy and exhaled nitric oxide in a cohort of 6-yr-old New Zealand children.

    PubMed

    Crane, Julian; Lampshire, Philippa; Wickens, Kristin; Epton, Michael; Siebers, Robert; Ingham, Tristram; Pattemore, Philip; Town, Ian

    2012-02-01

    Exhaled nitric oxide has been promoted as a non-invasive measure of airway inflammation, with clinical utility for the diagnosis and management of asthma. We studied associations between exhaled nitric oxide, asthma and atopy in a variety of clinically relevant phenotypes in a cohort of 6-yr-old children. Asthma was defined using standard questionnaire criteria, atopy was measured using skin prick tests (SPT) and specific IgE to common allergens, and exhaled nitric oxide was measured using a chemiluminescence analyser according to American and European Thoracic Society criteria. Exhaled nitric oxide was strongly related to atopy and in particular to sensitization to house dust mites. Children with non-allergic asthma had no increase in exhaled nitric oxide compared with non-asthmatic children. Compared with children who never wheezed both late onset and persistent, wheezing was associated with increased FE(NO), while early transient wheezing was not. Elevated levels of exhaled nitric oxide amongst children with allergic asthma were almost entirely explained by their levels of specific IgE to aeroallergens, predominantly D pteronyssinus. Airway inflammation as measured by exhaled nitric oxide in young New Zealand children is related to their level of specific IgE to aeroallergens. This has implications for the utility of nitric oxide as a diagnostic and management tool in childhood asthma and for the importance of specific IgE as a marker of asthma severity. © 2011 John Wiley & Sons A/S.

  19. 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

  20. Reverse Distal Transverse Palmar Arch in Distal Digital Replantation.

    PubMed

    Wei, Ching-Yueh; Orozco, Oscar; Vinagre, Gustavo; Shafarenko, Mark

    2017-07-22

    Refinements in microsurgery have made distal finger replantation an established technique with high success rates and good functional and aesthetic outcomes. However, it still represents a technically demanding procedure due to the small vessel caliber and frequent lack of vessel length, requiring the use of interpositional venous grafts in some instances. We describe a new technique for anastomosis in fingertip replantation, whereby the need for venous grafts is eliminated. Applying the reverse distal transverse palmar arch technique, 11 cases of distal digital replantation were performed between January 2011 and July 2016. The described procedure was used for arterial anastomosis in 10 cases and arteriovenous shunting for venous drainage in 1 case. A retrospective case review was conducted. The technical description and clinical outcome evaluations are presented. Ten of the 11 replanted digits survived, corresponding to an overall success rate of 91%. One replant failed due to venous insufficiency. Blood transfusions were not required for any of the patients. Follow-up (range, 1.5-5 months) revealed near-normal range of motion and good aesthetic results. All of the replanted digits developed protective sensation. The average length of hospital admission was 5 days. All patients were satisfied with the results and were able to return to their previous work. The use of the reverse distal transverse palmar arch is a novel and reliable technique in distal digital replantation when an increase in vessel length is required, allowing for a tension-free arterial repair without the need for vein grafts.

  1. Chlorine gas exposure disrupts nitric oxide homeostasis in the pulmonary vasculature

    PubMed Central

    Honavar, Jaideep; Bradley, Eddie; Bradley, Kelley; Oh, Joo Yeun; Vallejo, Matthew O.; Kelley, Eric E.; Cantu-Medellin, Nadiezhda; Doran, Stephen; Dell’italia, Louis J.; Matalon, Sadis; Patel, Rakesh P.

    2014-01-01

    Exposure to chlorine (Cl2) gas during industrial accidents or chemical warfare leads to significant airway and distal lung epithelial injury that continues post exposure. While lung epithelial injury is prevalent, relatively little is known about whether Cl2 gas also promotes injury to the pulmonary vasculature. To determine this, rats were subjected to a sub-lethal Cl2 gas exposure (400ppm, 30min) and then brought back to room air. Pulmonary arteries (PA) were isolated from rats at various times post-exposure and contractile (phenylephrine) and nitric oxide (NO)-dependent vasodilation (acetylcholine and mahmanonoate) responses measured ex-vivo. PA contractility did not change, however significant inhibition of NO-dependent vasodilation was observed that was maximal at 24–48 hours post exposure. Superoxide dismutase restored NO-dependent vasodilation suggesting a role for increased superoxide formation. This was supported by ~2-fold increase in superoxide formation (measured using 2-hydroethidine oxidation to 2-OH-E+) from PA isolated from Cl2 exposed rats. We next measured PA pressures in anesthetized rats. Surprisingly, PA pressures were significantly (~4mmHg) lower in rats that had been exposed to Cl2 gas 24 hours earlier suggesting that deficit in NO-signaling observed in isolated PA experiments did not manifest as increased PA pressures in vivo. Administration of the iNOS selective inhibitor 1400W, restored PA pressures to normal in Cl2 exposed, but not control rats suggesting that any deficit in NO-signaling due to increased superoxide formation in the PA, is offset by increased NO-formation from iNOS. These data indicate that disruption of endogenous NO-signaling mechanisms that maintain PA tone is an important aspect of post-Cl2 gas exposure toxicity. PMID:24769334

  2. Distribution of airway narrowing responses across generations and at branching points, assessed in vitro by anatomical optical coherence tomography

    PubMed Central

    2010-01-01

    Background Previous histological and imaging studies have shown the presence of variability in the degree of bronchoconstriction of airways sampled at different locations in the lung (i.e., heterogeneity). Heterogeneity can occur at different airway generations and at branching points in the bronchial tree. Whilst heterogeneity has been detected by previous experimental approaches, its spatial relationship either within or between airways is unknown. Methods In this study, distribution of airway narrowing responses across a portion of the porcine bronchial tree was determined in vitro. The portion comprised contiguous airways spanning bronchial generations (#3-11), including the associated side branches. We used a recent optical imaging technique, anatomical optical coherence tomography, to image the bronchial tree in three dimensions. Bronchoconstriction was produced by carbachol administered to either the adventitial or luminal surface of the airway. Luminal cross sectional area was measured before and at different time points after constriction to carbachol and airway narrowing calculated from the percent decrease in luminal cross sectional area. Results When administered to the adventitial surface, the degree of airway narrowing was progressively increased from proximal to distal generations (r = 0.80 to 0.98, P < 0.05 to 0.001). This 'serial heterogeneity' was also apparent when carbachol was administered via the lumen, though it was less pronounced. In contrast, airway narrowing was not different at side branches, and was uniform both in the parent and daughter airways. Conclusions Our findings demonstrate that the bronchial tree expresses intrinsic serial heterogeneity, such that narrowing increases from proximal to distal airways, a relationship that is influenced by the route of drug administration but not by structural variations accompanying branching sites. PMID:20092657

  3. Distal gastrectomy versus total gastrectomy for distal gastric cancer

    PubMed Central

    Liu, Zhen; Feng, Fan; Guo, Man; Liu, Shushang; Zheng, Gaozan; Xu, Guanghui; Lian, Xiao; Fan, Daiming; Zhang, Hongwei

    2017-01-01

    Abstract Even though more than a century later, after the first case of gastrectomy has been successfully performed, the best surgical treatment for distal gastric cancer still remains controversial. Thus, the present study was designed to compare the survival impact of distal (DG) or total gastrectomy (TG) for distal gastric cancer. A total of 1262 distal gastric cancer patients were enrolled in current study including 1157 patients who underwent DG and 157 patients who underwent TG. The postoperative complications and 5-year overall survival were compared between the 2 groups. TG group presented a longer surgical time, a higher volume of intraoperative bleeding, and a larger number of excised lymph nodes (all P < 0.05) compared with the DG group. The postoperative complications were comparable (all P >0.05). The 5-year overall survival rate of DG group was significantly higher than that of TG group (67.6% vs 44.3%, P < 0.001). However, multivariate analysis showed that type of resection was not an independent prognostic factor for distal gastric cancer (P > 0.05). The factor-stratified multivariate analysis showed that only in the subgroup of Tumor-node-metastasis staging system (TNM) stage III (P = 0.049), TG was the independent prognostic factor for poor survival. In conclusion, DG was as feasible as TG; however, TG did not increase the survival rate. DG brought better long-term survival than TG in patients with TNM stage III tumor. We recommended that DG should be the optimal surgical procedure for distal gastric cancer under the premise of negative resection margin. PMID:28151896

  4. Continuous Positive Airway Pressure Strategies with Bubble Nasal Continuous Positive Airway Pressure: Not All Bubbling Is the Same: The Seattle Positive Airway Pressure System.

    PubMed

    Welty, Stephen E

    2016-12-01

    Premature neonates are predisposed to complications, including bronchopulmonary dysplasia (BPD). BPD is associated with long-term pulmonary and neurodevelopmental consequences. Noninvasive respiratory support with nasal continuous positive airway pressure (CPAP) has been recommended strongly by the American Academy of Pediatrics. However, CPAP implementation has shown at least a 50% failure rate. Enhancing nasal CPAP effectiveness may decrease the need for mechanical ventilation and reduce the incidence of BPD. Bubble nasal CPAP is better than nasal CPAP using mechanical devices and the bubbling provides air exchange in distal respiratory units. The Seattle PAP system reduces parameters that assess work of breathing. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Assessment of airway inflammation with exhaled NO measurement

    PubMed Central

    Hatziagorou, E; Tsanakas, J

    2007-01-01

    Assessing airway inflammation is important for investigating the underlying mechanisms of many lung diseases, including asthma, chronic obstructive pulmonary disease (COPD), bronchiectasis, primary ciliary dyskinesia (PCD) and cystic fibrosis. A growing interest has recently directed toward non-invasive methods for the assessment of airway inflammation. Measurement of exhaled nitric oxide in exhaled air is an exciting innovative technique that gives new insights into the pathophysiology of lung disease and asthma in particular, with many potential clinical applications. Careful standardisation of measurement techniques has facilitated the use of this new measurement in paediatric respiratory medicine. Non-invasiveness and instantaneous results potentially make it a suitable instrument for use in children starting from the age of 4, with useful applications both in asthma diagnosis and monitoring. PMID:19582178

  6. Unrecognized failed airway management using a supraglottic airway device.

    PubMed

    Vithalani, Veer D; Vlk, Sabrina; Davis, Steven Q; Richmond, Neal J

    2017-10-01

    911 Emergency Medical Services (EMS) systems utilize supraglottic devices for either primary advanced airway management, or for airway rescue following failed attempts at direct laryngoscopy endotracheal intubation. There is, however, limited data on objective confirmation of supraglottic airway placement in the prehospital environment. Furthermore, the ability of EMS field providers to recognize a misplaced airway is unknown. Retrospective review of patients who underwent airway management using the King LTS-D supraglottic airway in a large urban EMS system, between 3/1/15-9/30/2015. Subjective success was defined as documentation of successful airway placement by the EMS provider. Objective success was confirmed by review of waveform capnography, with the presence of a 4-phase waveform greater than 5mmHg. Sensitivity and specificity of the field provider's assessment of success were then calculated. A total of 344 supraglottic airway attempts were reviewed. No patients met obvious death criteria. 269 attempts (85.1%) met criteria for both subjective and objective success. 19 attempts (5.6%) were recognized failures by the EMS provider. 47 (13.8%) airways were misplaced but unrecognized by the EMS provider. 4 attempts (1.2%) were correctly placed but misidentified as failures, leading to the unnecessary removal and replacement of the airway. Sensitivity of the provider's assessment was 98.5%; specificity was 28.7%. The use of supraglottic airway devices results in unrecognized failed placement. Appropriate utilization and review of waveform capnography may remedy a potential blind-spot in patient safety, and systemic monitoring/feedback processes may therefore be used to prevent unrecognized misplaced airways. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Leukotrienes and airway inflammation

    PubMed Central

    Okunishi, Katsuhide; Peters-Golden, Marc

    2011-01-01

    Asthma is a common chronic inflammatory disease of the airways characterized by airway obstruction and hyperresponsiveness. Leukotrienes (LTs) are lipid mediators that contribute to many aspects of asthma pathogenesis. As the LT pathway is relatively steroid-resistant, its blockade by alternative strategies is a desirable component of asthma management. Cysteinyl LT receptor 1 antagonists have been utilized worldwide for more than 10 years, and while their efficacy in asthma is well accepted, their limitations are also evident. In this review, we summarize the biological effects of LTs in asthma, review recent advances in LT receptors, and consider possible new therapeutic targets in the LT pathway that offer the potential to achieve better control of asthma in the future. PMID:21352897

  8. 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

  9. Using biomarkers in the assessment of airways disease.

    PubMed

    Taylor, D Robin

    2011-11-01

    A biomarker provides a window on underlying disease activity. This is helpful when the pathology, treatment response, or both are heterogeneous or when trying to interpret nonspecific respiratory symptoms in patients with comorbidities. The successful application of a biomarker result is critically dependent on the specific question being addressed and the performance characteristics of the biomarker in relation to that question in the context of pretest probabilities. Negative prediction might be the best way to use a biomarker, such as a D-dimer, pro-brain natriuretic peptide, and exhaled nitric oxide. In this review the role of biomarkers in airways disease (notably induced sputum eosinophils and exhaled nitric oxide) is considered in relation to risk stratification, identification of treatment responders, identification of a clinical phenotype, monitoring of disease, and new drug development.

  10. 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.

  11. Traumatic Distal Ulnar Artery Thrombosis

    PubMed Central

    Karaarslan, Ahmet A.; Karakaşlı, Ahmet; Mayda, Aslan; Karcı, Tolga; Aycan, Hakan; Kobak, Şenol

    2014-01-01

    This paper is about a posttraumatic distal ulnar artery thrombosis case that has occurred after a single blunt trauma. The ulnar artery thrombosis because of chronic trauma is a frequent condition (hypothenar hammer syndrome) but an ulnar artery thrombosis because of a single direct blunt trauma is rare. Our patient who has been affected by a single blunt trauma to his hand and developed ulnar artery thrombosis has been treated by resection of the thrombosed ulnar artery segment. This report shows that a single blunt trauma can cause distal ulnar artery thrombosis in the hand and it can be treated merely by thrombosed segment resection in suitable cases. PMID:25276455

  12. Chloride and potassium channels in cystic fibrosis airway epithelia

    NASA Astrophysics Data System (ADS)

    Welsh, Michael J.; Liedtke, Carole M.

    1986-07-01

    Cystic fibrosis, the most common lethal genetic disease in Caucasians, is characterized by a decreased permeability in sweat gland duct and airway epithelia. In sweat duct epithelium, a decreased Cl- permeability accounts for the abnormally increased salt content of sweat1. In airway epithelia a decreased Cl- permeability, and possibly increased sodium absorption, may account for the abnormal respiratory tract fluid2,3. The Cl- impermeability has been localized to the apical membrane of cystic fibrosis airway epithelial cells4. The finding that hormonally regulated Cl- channels make the apical membrane Cl- permeable in normal airway epithelial cells5 suggested abnormal Cl- channel function in cystic fibrosis. Here we report that excised, cell-free patches of membrane from cystic fibrosis epithelial cells contain Cl- channels that have the same conductive properties as Cl- channels from normal cells. However, Cl- channels from cystic fibrosis cells did not open when they were attached to the cell. These findings suggest defective regulation of Cl- channels in cystic fibrosis epithelia; to begin to address this issue, we performed two studies. First, we found that isoprenaline, which stimulates Cl- secretion, increases cellular levels of cyclic AMP in a similar manner in cystic fibrosis and non-cystic fibrosis epithelial cells. Second, we show that adrenergic agonists open calcium-activated potassium channels, indirectly suggesting that calcium-dependent stimulus-response coupling is intact in cystic fibrosis. These data suggest defective regulation of Cl- channels at a site distal to cAMP accumulation.

  13. The airway, breathing and orthodontics.

    PubMed

    Page, David C; Mahony, Derek

    2010-01-01

    Dentists need to play a bigger role in managing airway development and craniofacial formation even though the relationship between the airway, breathing and malocclusion remains quite controversial. Certainly the airway, the mode of breathing and craniofacial formation are so interrelated during growth and development that form can follow function and function can follow form. So, it is imperative to normalize form and function as early as possible so that function is optimized for life.

  14. 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.

  15. Airway Management of Respiratory Failure.

    PubMed

    Overbeck, Michael C

    2016-02-01

    Patients in respiratory distress often require airway management, including endotracheal intubation. It takes a methodical approach to transition from an unstable patient in distress with an unsecured airway, to a stable, sedated patient with a definitive airway. Through a deliberate course of advanced preparation, the emergency physician can tailor the approach to the individual clinical situation and optimize the chance of first-pass success. Sedation of the intubated patient confers physiologic benefits and should be included in the plan for airway control. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. An official ATS clinical practice guideline: interpretation of exhaled nitric oxide levels (FENO) for clinical applications.

    PubMed

    Dweik, Raed A; Boggs, Peter B; Erzurum, Serpil C; Irvin, Charles G; Leigh, Margaret W; Lundberg, Jon O; Olin, Anna-Carin; Plummer, Alan L; Taylor, D Robin

    2011-09-01

    Measurement of fractional nitric oxide (NO) concentration in exhaled breath (Fe(NO)) is a quantitative, noninvasive, simple, and safe method of measuring airway inflammation that provides a complementary tool to other ways of assessing airways disease, including asthma. While Fe(NO) measurement has been standardized, there is currently no reference guideline for practicing health care providers to guide them in the appropriate use and interpretation of Fe(NO) in clinical practice. To develop evidence-based guidelines for the interpretation of Fe(NO) measurements that incorporate evidence that has accumulated over the past decade. We created a multidisciplinary committee with expertise in the clinical care, clinical science, or basic science of airway disease and/or NO. The committee identified important clinical questions, synthesized the evidence, and formulated recommendations. Recommendations were developed using pragmatic systematic reviews of the literature and the GRADE approach. The evidence related to the use of Fe(NO) measurements is reviewed and clinical practice recommendations are provided. In the setting of chronic inflammatory airway disease including asthma, conventional tests such as FEV(1) reversibility or provocation tests are only indirectly associated with airway inflammation. Fe(NO) offers added advantages for patient care including, but not limited to (1) detecting of eosinophilic airway inflammation, (2) determining the likelihood of corticosteroid responsiveness, (3) monitoring of airway inflammation to determine the potential need for corticosteroid, and (4) unmasking of otherwise unsuspected nonadherence to corticosteroid therapy.

  17. [Fractures of the distal radius].

    PubMed

    Rueger, J M; Hartel, M J; Ruecker, A H; Hoffmann, M

    2014-11-01

    The most prevalent fractures managed by trauma surgeons are those involving the distal radius. The injury occurs in two peaks of prevalence: the first peak around the age of 10 years and the second peak around the age of 60 years. Distal radius fracture management requires sensitive diagnostics and classification. The objectives of treatment are the reconstruction of a pain-free unlimited durable functioning of the wrist and avoidance of typical fracture complications. Non-operative conservative management is generally employed for stable non-displaced fractures of the distal radius with the expectation of a good functional outcome. Unstable comminuted fractures with intra-articular and extra-articular fragment zones are initially set in a closed operation and finally by osteosynthesis. An armament of surgical implants is available for instable fractures requiring fixation. Palmar locked plate osteosynthesis has been established in recent years as the gold standard for operative management of distal radius fractures. Complex Working Group on Osteosynthesis (AO) classification type 3 fractures require extensive preoperative diagnostics to identify and treat typical associated injuries around the wrist.

  18. Application of nitric oxide measurements in clinical conditions beyond asthma

    PubMed Central

    Malinovschi, Andrei; Ludviksdottir, Dora; Tufvesson, Ellen; Rolla, Giovanni; Bjermer, Leif; Alving, Kjell; Diamant, Zuzana

    2015-01-01

    Fractional exhaled nitric oxide (FeNO) is a convenient, non-invasive method for the assessment of active, mainly Th2-driven, airway inflammation, which is sensitive to treatment with standard anti-inflammatory therapy. Consequently, FeNO serves as a valued tool to aid diagnosis and monitoring in several asthma phenotypes. More recently, FeNO has been evaluated in several other respiratory, infectious, and/or immunological conditions. In this short review, we provide an overview of several clinical studies and discuss the status of potential applications of NO measurements in clinical conditions beyond asthma. PMID:26672962

  19. Fractional exhaled nitric oxide-measuring devices: technology update

    PubMed Central

    Maniscalco, Mauro; Vitale, Carolina; Vatrella, Alessandro; Molino, Antonio; Bianco, Andrea; Mazzarella, Gennaro

    2016-01-01

    The measurement of exhaled nitric oxide (NO) has been employed in the diagnosis of specific types of airway inflammation, guiding treatment monitoring by predicting and assessing response to anti-inflammatory therapy and monitoring for compliance and detecting relapse. Various techniques are currently used to analyze exhaled NO concentrations under a range of conditions for both health and disease. These include chemiluminescence and electrochemical sensor devices. The cost effectiveness and ability to achieve adequate flexibility in sensitivity and selectivity of NO measurement for these methods are evaluated alongside the potential for use of laser-based technology. This review explores the technologies involved in the measurement of exhaled NO. PMID:27382340

  20. Mucoactive agents for airway mucus hypersecretory diseases.

    PubMed

    Rogers, Duncan F

    2007-09-01

    Airway mucus hypersecretion is a feature of a number of severe respiratory diseases, including asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF). However, each disease has a different airway inflammatory response, with consequent, and presumably linked, mucus hypersecretory phenotype. Thus, it is possible that optimal treatment of the mucus hypersecretory element of each disease should be disease-specific. Nevertheless, mucoactive drugs are a longstanding and popular therapeutic option, and numerous compounds (eg, N-acetylcysteine, erdosteine, and ambroxol) are available for clinical use worldwide. However, rational recommendation of these drugs in guidelines for management of asthma, COPD, or CF has been hampered by lack of information from well-designed clinical trials. In addition, the mechanism of action of most of these drugs is unknown. Consequently, although it is possible to categorize them according to putative mechanisms of action, as expectorants (aid and/or induce cough), mucolytics (thin mucus), mucokinetics (facilitate cough transportability), and mucoregulators (suppress mechanisms underlying chronic mucus hypersecretion, such as glucocorticosteroids), it is likely that any beneficial effects are due to activities other than, or in addition to, effects on mucus. It is also noteworthy that the mucus factors that favor mucociliary transport (eg, thin mucus gel layer, "ideal" sol depth, and elasticity greater than viscosity) are opposite to those that favor cough effectiveness (thick mucus layer, excessive sol height, and viscosity greater than elasticity), which indicates that different mucoactive drugs would be required for treatment of mucus obstruction in proximal versus distal airways, or in patients with an impaired cough reflex. With the exception of mucoregulatory agents, whose primary action is unlikely to be directed against mucus, well-designed clinical trials are required to unequivocally determine the

  1. [Airway management in obstetrics].

    PubMed

    Boutonnet, M; Faitot, V; Keïta, H

    2011-09-01

    Reviewing problems related to the airway management in obstetrics, taking into account the recent evolutions of the anaesthetic practices in obstetrics. A review of the literature in English and French was performed in the Pumed database in April 2010. The first research used the following MeshTerms: "Anesthesia, Obstetrical" [Mesh] AND "Intubation, Intratracheal" [Mesh]. Complementary research used alone or in combination the following keywords: difficult tracheal intubation; failed tracheal intubation; airway; prediction of difficult tracheal intubation; maternal mortality; maternal morbidity; liability; aspiration pneumonia and obstetrical anesthesia. All the publications were retained excluding the correspondence. Data analysis for the airway management in obstetrics, the prediction of difficult intubation, the prevention of pulmonary inhalation of gastric fluid, but also on maternal morbi-mortality in link with general anesthesia in obstetrics. Airway management in obstetrics remains a true challenge for various reasons. The physiological and anatomical modifications related to pregnancy are responsible for a faster hypoxemia, a reduction of the diameter of the pharyngolaryngal tract, as well as an increase of the risk of inhalation of gastric contents after 16 weeks of amenorrhea. The emergency or extreme emergency context and the presence of diseases like obesity or preeclampsia raise the risks of difficulties with airway management. The logical evolution of the practices, with the considerable rise of the regional anesthesia/analgesia limits the training and the maintenance of competences for intratracheal intubation in obstetrics. The training per simulation appears particularly interesting on the subject and this approach needs to be developed. The literature indicates that the incidence of difficult intubation is of one per 30. The impossible intubation is one per 280 in obstetrics, eight times greater than in the general population. No criterion of

  2. 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.

  3. Extraglottic airway devices: technology update

    PubMed Central

    Sharma, Bimla; Sahai, Chand; Sood, Jayashree

    2017-01-01

    Extraglottic airway devices (EADs) have revolutionized the field of airway management. The invention of the laryngeal mask airway was a game changer, and since then, there have been several innovations to improve the EADs in design, functionality, safety and construction material. These have ranged from changes in the shape of the mask, number of cuffs and material used, like rubber, polyvinylchloride and latex. Phthalates, which were added to the construction material in order to increase device flexibility, were later omitted when this chemical was found to have serious adverse reproductive outcomes. The various designs brought out by numerous companies manufacturing EADs resulted in the addition of several devices to the airway market. These airway devices were put to use, many of them with inadequate or no evidence base regarding their efficacy and safety. To reduce the possibility of compromising the safety of the patient, the Difficult Airway Society (DAS) formed the Airway Device Evaluation Project Team (ADEPT) to strengthen the evidence base for airway equipment and vet the new extraglottic devices. A preuse careful analysis of the design and structure may help in better understanding of the functionality of a particular device. In the meantime, the search for the ideal EAD continues. PMID:28860875

  4. Recurrent airway obstruction: a review.

    PubMed

    Pirie, R S

    2014-05-01

    Recurrent airway obstruction is a widely recognised airway disorder, characterised by hypersensitivity-mediated neutrophilic airway inflammation and lower airway obstruction in a subpopulation of horses when exposed to suboptimal environments high in airborne organic dust. Over the past decade, numerous studies have further advanced our understanding of different aspects of the disease. These include clarification of the important inhaled airborne agents responsible for disease induction, improving our understanding of the underlying genetic basis of disease susceptibility and unveiling the fundamental immunological mechanisms leading to establishment of the classic disease phenotype. This review, as well as giving a clinical overview of recurrent airway obstruction, summarises much of the work in these areas that have culminated in a more thorough understanding of this debilitating disease.

  5. 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

  6. Global airway disease beyond allergy.

    PubMed

    Hellings, Peter W; Prokopakis, Emmanuel P

    2010-03-01

    Besides the anatomic continuity of the upper and lower airways, inflammation in one part of the airway influences the homeostasis of the other. The mechanisms underlying this interaction have been studied primarily in allergic disease, showing systemic immune activation, induction of inflammation at a distance, and a negative impact of nasal inflammation on bronchial homeostasis. In addition to allergy, other inflammatory conditions of the upper airways are associated with lower airway disease. Rhinosinusitis is frequently associated with asthma and chronic obstructive pulmonary disease. The impairment of purification, humidification, and warming up of the inspired air by the nose in rhinosinusitis may be responsible in part for bronchial pathology. The resolution of sinonasal inflammation via medical and/or surgical treatment is responsible for the beneficial effect of the treatment on bronchial disease. This article provides a comprehensive overview of the current knowledge of upper and lower airway communication beyond allergic disease.

  7. The airway microbiome and disease.

    PubMed

    Marsland, Benjamin J; Yadava, Koshika; Nicod, Laurent P

    2013-08-01

    Although traditionally thought to be sterile, accumulating evidence now supports the concept that our airways harbor a microbiome. Thus far, studies have focused upon characterizing the bacterial constituents of the airway microbiome in both healthy and diseased lungs, but what perhaps provides the greatest impetus for the exploration of the airway microbiome is that different bacterial phyla appear to dominate diseased as compared with healthy lungs. As yet, there is very limited evidence supporting a functional role for the airway microbiome, but continued research in this direction is likely to provide such evidence, particularly considering the progress that has been made in understanding host-microbe mutualism in the intestinal tract. In this review, we highlight the major advances that have been made discovering and describing the airway microbiome, discuss the experimental evidence that supports a functional role for the microbiome in health and disease, and propose how this emerging field is going to impact clinical practice.

  8. Arginase activity and nitric oxide levels in patients with obstructive sleep apnea syndrome.

    PubMed

    Yüksel, Meral; Okur, Hacer Kuzu; Pelin, Zerrin; Öğünç, Ayliz Velioğlu; Öztürk, Levent

    2014-01-01

    Obstructive sleep apnea syndrome is characterized by repetitive obstruction of the upper airways, and it is a risk factor for cardiovascular diseases. There have been several studies demonstrating low levels of nitric oxide in patients with obstructive sleep apnea syndrome compared with healthy controls. In this study, we hypothesized that reduced nitric oxide levels would result in high arginase activity. Arginase reacts with L-arginine and produces urea and L-ornithine, whereas L-arginine is a substrate for nitric oxide synthase, which produces nitric oxide. The study group consisted of 51 obstructive sleep apnea syndrome patients (M/F: 43/8; mean age 49±10 years of age) and 15 healthy control subjects (M/F: 13/3; mean age 46±14 years of age). Obstructive sleep apnea syndrome patients were divided into two subgroups based on the presence or absence of cardiovascular disease. Nitric oxide levels and arginase activity were measured via an enzyme-linked immunosorbent assay of serum samples. Serum nitric oxide levels in the control subjects were higher than in the obstructive sleep apnea patients with and without cardiovascular diseases (p<0.05). Arginase activity was significantly higher (p<0.01) in obstructive sleep apnea syndrome patients without cardiovascular diseases compared with the control group. Obstructive sleep apnea syndrome patients with cardiovascular diseases had higher arginase activity than the controls (p<0.001) and the obstructive sleep apnea syndrome patients without cardiovascular diseases (p<0.05). Low nitric oxide levels are associated with high arginase activity. The mechanism of nitric oxide depletion in sleep apnea patients suggests that increased arginase activity might reduce the substrate availability of nitric oxide synthase and thus could reduce nitric oxide levels.

  9. Aerosol bolus dispersion in acinar airways--influence of gravity and airway asymmetry.

    PubMed

    Ma, Baoshun; Darquenne, Chantal

    2012-08-01

    The aerosol bolus technique can be used to estimate the degree of convective mixing in the lung; however, contributions of different lung compartments to measured dispersion cannot be differentiated unambiguously. To estimate dispersion in the distal lung, we studied the effect of gravity and airway asymmetry on the dispersion of 1 μm-diameter particle boluses in three-dimensional computational models of the lung periphery, ranging from a single alveolar sac to four-generation (g4) structures of bifurcating airways that deformed homogeneously during breathing. Boluses were introduced at the beginning of a 2-s inhalation, immediately followed by a 3-s exhalation. Dispersion was estimated by the half-width of the exhaled bolus. Dispersion was significantly affected by the spatial orientation of the models in normal gravity and was less in zero gravity than in normal gravity. Dispersion was strongly correlated with model volume in both normal and zero gravity. Predicted pulmonary dispersion based on a symmetric g4 acinar model was 391 ml and 238 ml under normal and zero gravity, respectively. These results accounted for a significant amount of dispersion measured experimentally. In zero gravity, predicted dispersion in a highly asymmetric model accounted for ∼20% of that obtained in a symmetric model with comparable volume and number of alveolated branches, whereas normal gravity dispersions were comparable in both models. These results suggest that gravitational sedimentation and not geometrical asymmetry is the dominant factor in aerosol dispersion in the lung periphery.

  10. Distal clavicle fractures in children☆

    PubMed Central

    Labronici, Pedro José; da Silva, Ricardo Rodrigues; Franco, Marcos Vinícius Viana; Labronici, Gustavo José; Pires, Robinson Esteves Santos; Franco, José Sergio

    2015-01-01

    Objective To analyze fractures of the distal clavicle region in pediatric patients. Methods Ten patients between the ages of five to eleven years (mean of 7.3 years) were observed. Nine patients were treated conservatively and one surgically. All the fractures were classified using the Nenopoulos classification system. Results All the fractures consolidated without complications. Conservative treatment was used for nine patients, of whom three were in group IIIB, three IIb, two IIa and one IV. The only patient who was treated surgically was a female patient of eleven years of age with a group IV fracture. Conclusion The treatment indication for distal fractures of the clavicle in children should be based on the patient's age and the displacement of the fragments. PMID:26962489

  11. [Distal radius fractures in children].

    PubMed

    Otayek, S; Ramanoudjame, M; Fitoussi, F

    2016-12-01

    Metaphyseal and physeal fractures of the distal radius are common in children. Most cases are best treated with closed reduction and cast immobilization. Long-term outcomes of these injuries are excellent when specific treatment principles of reduction and casting are followed. Surgical indications are limited and include open fractures, intra-articular fractures, non-reducible fractures, unstable fractures, and the presence of associated nerve injury. Closed reduction and percutaneous pin fixation is the most commonly used surgical option. The clinician should be aware of delayed complications such as growth disturbance of the distal radius, and understand how to manage these problems to ensure successful long-term outcomes. Epiphysiodesis is uncommon but growth plate injuries need to be followed for one year.

  12. Airway management during cardiopulmonary resuscitation.

    PubMed

    Bernhard, Michael; Benger, Jonathan R

    2015-06-01

    This article evaluates the latest scientific evidence regarding airway management during in-hospital and out-of-hospital cardiopulmonary resuscitation (CPR). In the in-hospital setting, observational research suggested that the quality of CPR using 'no flow ratio' as a surrogate marker was improved when advanced airway techniques were used. A registry study demonstrated that an initial failed intubation attempt was associated with an average delay of 3 min in time to return of spontaneous circulation. A prospective observational study showed that the Glide Scope videolaryngoscope was associated with a first-pass success rate of 93%, with no differences between less and more experienced physicians. In the out-of-hospital setting, a registry study suggested that intubation leads to a better outcome compared with supraglottic airway devices. However, no advanced airway devices showed a better outcome than basic airway techniques. An observational study reported that the i-gel supraglottic airway device offers a first-pass insertion success rate of 90%, and was easier to establish than the Portex Soft Seal laryngeal mask airway. Other out-of-hospital observational studies showed that the laryngeal tube offers a lower first-pass insertion success rate than expected, and complications of this device may influence later definitive airway management and the outcome as a whole. Recent studies of airway management during CPR rely mostly on registry and observational designs. Prospective randomized trials are needed to determine the optimal approach to airway management during cardiac arrest, but have not yet been completed.

  13. Endoscopic Distal Tibiofibular Syndesmosis Arthrodesis.

    PubMed

    Lui, Tun Hing

    2016-04-01

    Chronic distal tibiofibular syndesmosis disruption can be managed by endoscopic arthrodesis of the syndesmosis. This is performed through the proximal anterolateral and posterolateral portals. The scar tissue and bone block are resected to facilitate the subsequent reduction of the syndesmosis. The reduction of the syndesmosis can be guided either arthroscopically or endoscopically. The tibial and fibular surfaces of the tibiofibular overlap can be microfractured to facilitate subsequent fusion.

  14. Distal anterior cerebral artery aneurysms.

    PubMed

    Lehecka, Martin; Dashti, Reza; Lehto, Hanna; Kivisaari, Riku; Niemelä, Mika; Hernesniemi, Juha

    2010-01-01

    Distal anterior cerebral artery (DACA) aneurysms, also known as pericallosal artery aneurysms, represent about 6% of all intracranial aneurysms. They are located on the A2-A5 segments of the anterior cerebral artery and on its distal branches. This paper summarizes present knowledge on radiological features, treatment options, treatment results, and long-term follow-up of DACA aneurysms. Typical features of DACA aneurysms are small size, broad base, and branches originating from the base. When ruptured, they cause intracerebral hematoma in nearly half of the cases. DACA aneurysms are nowadays more often treated with microsurgical clipping than endovascular coiling due to their distal location and morphologic features. With clipping the results are same or slightly better than for aneurysms at other locations, coiling is often associated with more complications than in other aneurysms. Clipping is a long-lasting treatment with very small recurrence rate, there is no long-term data available on efficacy of coiling yet. For ruptured DACA aneurysms the most important factors affecting outcome is the severity of initial bleeding and patient's age.

  15. The effect of disease and respiration on airway shape in patients with moderate persistent asthma.

    PubMed

    Montesantos, Spyridon; Katz, Ira; Venegas, Jose; Pichelin, Marine; Caillibotte, Georges

    2017-01-01

    Computational models of gas transport and aerosol deposition frequently utilize idealized models of bronchial tree structure, where airways are considered a network of bifurcating cylinders. However, changes in the shape of the lung during respiration affect the geometry of the airways, especially in disease conditions. In this study, the internal airway geometry was examined, concentrating on comparisons between mean lung volume (MLV) and total lung capacity (TLC). A set of High Resolution CT images were acquired during breath hold on a group of moderate persistent asthmatics at MLV and TLC after challenge with a broncho-constrictor (methacholine) and the airway trees were segmented and measured. The airway hydraulic diameter (Dh) was calculated through the use of average lumen area (Ai) and average internal perimeter (Pi) at both lung volumes and was found to be systematically higher at TLC by 13.5±9% on average, with the lower lobes displaying higher percent change in comparison to the lower lobes. The average internal diameter (Din) was evaluated to be 12.4±6.8% (MLV) and 10.8±6.3% (TLC) lower than the Dh, for all the examined bronchi, a result displaying statistical significance. Finally, the airway distensibility per bronchial segment and per generation was calculated to have an average value of 0.45±0.28, exhibiting high variability both between and within lung regions and generations. Mixed constriction/dilation patterns were recorded between the lung volumes, where a number of airways either failed to dilate or even constricted when observed at TLC. We conclude that the Dh is higher than Din, a fact that may have considerable effects on bronchial resistance or airway loss at proximal regions. Differences in caliber changes between lung regions are indicative of asthma-expression variability in the lung. However, airway distensibility at generation 3 seems to predict distensibility more distally.

  16. 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

  17. 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

  18. Airway epithelial-derived factor relaxes pulmonary vascular smooth muscle.

    PubMed

    Farah, Omar R; Li, Dongge; McIntyre, Brendan A S; Pan, Jingyi; Belik, Jaques

    2009-01-01

    The factors controlling the pulmonary vascular resistance under physiological conditions are poorly understood. We have previously reported on an apparent cross talk between the airway and adjacent pulmonary arterial bed where a factor likely derived from the bronchial epithelial cells reduced the magnitude of agonist-stimulated force in the vascular smooth muscle. The main purpose of this investigation was to evaluate whether bronchial epithelial cells release a pulmonary arterial smooth muscle relaxant factor. Conditioned media from SPOC-1 or BEAS-2B, a rat- and a human-derived bronchial epithelial cell line, respectively, were utilized. This media significantly relaxed precontracted adult but not fetal pulmonary arterial muscle in an oxygen tension-dependent manner. This response was mediated via soluble guanylate cyclase, involving AKT/PI3-kinase and neuronal nitric oxide synthase. Airway epithelial cell-conditioned media increased AKT phosphorylation in pulmonary smooth muscle cells (SMC) and reduced intracellular calcium change following ATP stimulation to a significantly greater extent than observed for bronchial SMC. The present data strongly support the evidence for bronchial epithelial cells releasing a stable and soluble factor capable of inducing pulmonary arterial SMC relaxation. We speculate that under physiological conditions, the maintenance of a low pulmonary vascular resistance, postnatally, is in part modulated by the airway epithelium.

  19. Airway inflammation in probiotic-treated children at 5 years.

    PubMed

    Kukkonen, Anna K; Kuitunen, Mikael; Savilahti, Erkki; Pelkonen, Anna; Malmberg, Pekka; Mäkelä, Mika

    2011-03-01

    Early treatment of new-born high-risk children with certain probiotic strains has reduced the risk of atopic eczema. Whether probiotics reduce risk for airway inflammation in long term is not known. We aimed at studying the effect of probiotic treatment during the six first months of life on airway inflammation at age 5 yr. In a randomized double-blind allergy prevention trial between 2000 and 2007 in Helsinki, Finland, we gave a probiotic combination, plus pre-biotics, or placebo, to 1018 children during 6 months from birth. At age 5, we measured exhaled nitric oxide (FE(NO) ) in a randomized sub-population of 160 children. Allergic diseases and IgE-sensitization were assessed in all infants. FE(NO) did not differ between probiotic and placebo groups, median (interquartile range, IQR) 5.45 (4.3-7.3) vs. 5.70 (3.9-6.8) ppb, p = 0.22. FE(NO) was elevated among those suffering from asthma during the first 5 yr than in healthy non-sensitized children (p = 0.009). FE(NO) correlated positively with serum total and allergen-specific IgE concentrations. Early intervention with probiotics and pre-biotics does not affect airway inflammation later in childhood. © 2011 John Wiley & Sons A/S.

  20. Exhaled NO: Determinants and Clinical Application in Children With Allergic Airway Disease

    PubMed Central

    Kim, Hyo-Bin; Eckel, Sandrah P.

    2016-01-01

    Nitric oxide (NO) is endogenously released in the airways, and the fractional concentration of NO in exhaled breath (FeNO) is now recognized as a surrogate marker of eosinophilic airway inflammation that can be measured using a noninvasive technique suitable for young children. Although FeNO levels are affected by several factors, the most important clinical determinants of increased FeNO levels are atopy, asthma, and allergic rhinitis. In addition, air pollution is an environmental determinant of FeNO that may contribute to the high prevalence of allergic disease. In this review, we discuss the mechanism for airway NO production, methods for measuring FeNO, and determinants of FeNO in children, including host and environmental factors such as air pollution. We also discuss the clinical utility of FeNO in children with asthma and allergic rhinitis and further useful directions using FeNO measurement. PMID:26540497

  1. Telemedicine in British Airways.

    PubMed

    Bagshaw, M

    1996-01-01

    In the year ending March 1994, British Airways (BA) carried in excess of 30 million passengers worldwide. There was a total of 2078 reported in-flight medical incidents, with 18 unscheduled diversions for medical reasons. The commonest reported conditions were faints, diarrhoea and vomiting. The BA aircraft medical kit content exceeds the statutory minimum requirement and all cabin crew undergo training in first aid and life support. There is a BA doctor on 24 h call with whom an aircraft captain may communicate via a high-frequency radio link. This link has limitations and immediate contact is not always possible. BA is installing satellite communication facilities in new aircraft and the application of telemedicine utilizing this facility is being explored.

  2. Human airway organoid engineering as a step toward lung regeneration and disease modeling.

    PubMed

    Tan, Qi; Choi, Kyoung Moo; Sicard, Delphine; Tschumperlin, Daniel J

    2017-01-01

    Organoids represent both a potentially powerful tool for the study cell-cell interactions within tissue-like environments, and a platform for tissue regenerative approaches. The development of lung tissue-like organoids from human adult-derived cells has not previously been reported. Here we combined human adult primary bronchial epithelial cells, lung fibroblasts, and lung microvascular endothelial cells in supportive 3D culture conditions to generate airway organoids. We demonstrate that randomly-seeded mixed cell populations undergo rapid condensation and self-organization into discrete epithelial and endothelial structures that are mechanically robust and stable during long term culture. After condensation airway organoids generate invasive multicellular tubular structures that recapitulate limited aspects of branching morphogenesis, and require actomyosin-mediated force generation and YAP/TAZ activation. Despite the proximal source of primary epithelium used in the airway organoids, discrete areas of both proximal and distal epithelial markers were observed over time in culture, demonstrating remarkable epithelial plasticity within the context of organoid cultures. Airway organoids also exhibited complex multicellular responses to a prototypical fibrogenic stimulus (TGF-β1) in culture, and limited capacity to undergo continued maturation and engraftment after ectopic implantation under the murine kidney capsule. These results demonstrate that the airway organoid system developed here represents a novel tool for the study of disease-relevant cell-cell interactions, and establishes this platform as a first step toward cell-based therapy for chronic lung diseases based on de novo engineering of implantable airway tissues.

  3. Gene Delivery to the Airway

    PubMed Central

    Keiser, Nicholas W.; Engelhardt, John F.

    2013-01-01

    This unit describes generation of and gene transfer to several commonly used airway models. Isolation and transduction of primary airway epithelial cells are first described. Next, the preparation of polarized airway epithelial monolayers is outlined. Transduction of these polarized cells is also described. Methods are presented for generation of tracheal xenografts as well as both ex vivo and in vivo gene transfer to these xenografts. Finally, a method for in vivo gene delivery to the lungs of rodents is included. Methods for evaluating transgene expression are given in the support protocols. PMID:23853081

  4. Airway complications after lung transplantation.

    PubMed

    Machuzak, Michael; Santacruz, Jose F; Gildea, Thomas; Murthy, Sudish C

    2015-01-01

    Airway complications after lung transplantation present a formidable challenge to the lung transplant team, ranging from mere unusual images to fatal events. The exact incidence of complications is wide-ranging depending on the type of event, and there is still evolution of a universal characterization of the airway findings. Management is also wide-ranging. Simple observation or simple balloon bronchoplasty is sufficient in many cases, but vigilance following more severe necrosis is required for late development of both anastomotic and nonanastomotic airway strictures. Furthermore, the impact of coexisting infection, rejection, and medical disease associated with high-level immunosuppression further complicates care.

  5. Pulmonary Vascular Congestion: A Mechanism for Distal Lung Unit Dysfunction in Obesity

    PubMed Central

    Oppenheimer, Beno W.; Berger, Kenneth I.; Ali, Saleem; Segal, Leopoldo N.; Donnino, Robert; Katz, Stuart; Parikh, Manish; Goldring, Roberta M.

    2016-01-01

    Rationale Obesity is characterized by increased systemic and pulmonary blood volumes (pulmonary vascular congestion). Concomitant abnormal alveolar membrane diffusion suggests subclinical interstitial edema. In this setting, functional abnormalities should encompass the entire distal lung including the airways. Objectives We hypothesize that in obesity: 1) pulmonary vascular congestion will affect the distal lung unit with concordant alveolar membrane and distal airway abnormalities; and 2) the degree of pulmonary congestion and membrane dysfunction will relate to the cardiac response. Methods 54 non-smoking obese subjects underwent spirometry, impulse oscillometry (IOS), diffusion capacity (DLCO) with partition into membrane diffusion (DM) and capillary blood volume (VC), and cardiac MRI (n = 24). Alveolar-capillary membrane efficiency was assessed by calculation of DM/VC. Measurements and Main Results Mean age was 45±12 years; mean BMI was 44.8±7 kg/m2. Vital capacity was 88±13% predicted with reduction in functional residual capacity (58±12% predicted). Despite normal DLCO (98±18% predicted), VC was elevated (135±31% predicted) while DM averaged 94±22% predicted. DM/VC varied from 0.4 to 1.4 with high values reflecting recruitment of alveolar membrane and low values indicating alveolar membrane dysfunction. The most abnormal IOS (R5 and X5) occurred in subjects with lowest DM/VC (r2 = 0.31, p<0.001; r2 = 0.34, p<0.001). Cardiac output and index (cardiac output / body surface area) were directly related to DM/VC (r2 = 0.41, p<0.001; r2 = 0.19, p = 0.03). Subjects with lower DM/VC demonstrated a cardiac output that remained in the normal range despite presence of obesity. Conclusions Global dysfunction of the distal lung (alveolar membrane and distal airway) is associated with pulmonary vascular congestion and failure to achieve the high output state of obesity. Pulmonary vascular congestion and consequent fluid transudation and/or alterations in the

  6. Airway surface mycosis in chronic TH2-associated airway disease.

    PubMed

    Porter, Paul C; 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

    2014-08-01

    Environmental fungi have been linked to TH2 cell-related airway inflammation and the TH2-associated chronic airway diseases asthma, chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP), and allergic fungal rhinosinusitis (AFRS), but whether these organisms participate directly or indirectly in disease pathology remains unknown. To determine the frequency of fungus isolation and fungus-specific immunity in patients with TH2-associated and non-TH2-associated airway disease. Sinus lavage fluid and blood were collected from sinus surgery patients (n = 118) including patients with CRSwNP, patients with CRS without nasal polyps, patients with AFRS, and non-CRS/nonasthmatic control patients. Asthma status was determined from medical history. Sinus lavage fluids were cultured and directly examined for evidence of viable fungi. PBMCs were restimulated with fungal antigens in an enzyme-linked immunocell spot assay to determine total memory fungus-specific IL-4-secreting cells. These data were compared with fungus-specific IgE levels measured from plasma by ELISA. Filamentous fungi were significantly more commonly cultured in patients with TH2-associated airway disease (asthma, CRSwNP, or AFRS: n = 68) than in control patients with non-TH2-associated disease (n = 31): 74% vs 16%, respectively (P < .001). Both fungus-specific IL-4 enzyme-linked immunocell spot (n = 48) and specific IgE (n = 70) data correlated with TH2-associated diseases (sensitivity 73% and specificity 100% vs 50% and 77%, respectively). 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. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  7. NITRIC ACID PICKLING PROCESS

    DOEpatents

    Boller, E.R.; Eubank, L.D.

    1958-08-19

    An improved process is described for the treatment of metallic uranium surfaces preparatory to being given hot dip coatings. The process consists in first pickling the uraniunn surInce with aqueous 50% to 70% nitric acid, at 60 to 70 deg C, for about 5 minutes, rinsing the acid solution from the uranium article, promptly drying and then passing it through a molten alkali-metal halide flux consisting of 42% LiCl, 53% KCla and 5% NaCl into a molten metal bath consisting of 85 parts by weight of zinc and 15 parts by weight of aluminum

  8. Bilateral distal biceps tendon ruptures.

    PubMed

    Green, Jennifer B; Skaife, Tyler L; Leslie, Bruce M

    2012-01-01

    To determine the incidence of bilateral distal biceps tendon ruptures. A retrospective review of 321 patients who underwent operative repair of a distal biceps tendon rupture between 1988 and 2010 identified 26 patients with bilateral ruptures. We recorded patient age, mechanism of injury, time between symptom onset before the first surgery and subsequent contralateral symptoms, and time between surgeries. Twenty-two bilateral ruptures were confirmed intra-operatively, 3 by MRI, and 1 was lost to follow up. A total of 23 bilateral ruptures (92%) occurred in men. The average age at the initial rupture was 44 years (range, 29-74 y). The average age at subsequent rupture was 48 years (range, 36-79 y). Excluding the 2 women (age 72 and 79 y), the average age at the initial rupture was 42 years and the average age at subsequent rupture was 46 years. The average interval between ruptures was 4.1 years (range, 0.8-13.9 y). The initial rupture occurred in the dominant extremity in 12 cases (50%) and in the nondominant extremity in 10 cases (42%); in 3 patients (8%) the dominance was not documented or ambidextrous. Thirty-three percent were heavy laborers, 3 patients had a smoking history, and 1 patient reported a history of steroid use. Twenty-two patients (88%) had the second side repaired, where we noted that 12 (55%) of the second tendon ruptures were partial tears. The 8% cumulative incidence of bilateral biceps tendon ruptures in a consecutive series of biceps tendon repairs may be higher because not all patients were contacted, which introduced a sampling bias. This 8% rate is markedly higher than the reported rate of 1.2 per 100,000 for an isolated distal biceps tendon rupture. This implies that patients with a distal biceps tendon rupture are at risk for a rupture on the contralateral side. Prognostic III. Copyright © 2012 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

  9. Exhaled Nitric Oxide in Systemic Sclerosis Lung Disease

    PubMed Central

    Kozij, Natalie K.; Silkoff, Philip E.; Thenganatt, John; Chakravorty, Shobha

    2017-01-01

    Background. Exhaled nitric oxide (eNO) is a potential biomarker to distinguish systemic sclerosis (SSc) associated pulmonary arterial hypertension (PAH) and interstitial lung disease (ILD). We evaluated the discriminative validity, feasibility, methods of eNO measurement, and magnitude of differences across lung diseases, disease-subsets (SSc, systemic lupus erythematosus), and healthy-controls. Methods. Consecutive subjects in the UHN Pulmonary Hypertension Programme were recruited. Exhaled nitric oxide was measured at 50 mL/s intervals using chemiluminescent detection. Alveolar and conducting airway NO were partitioned using a two-compartment model of axial diffusion (CMAD) and the trumpet model of axial diffusion (TMAD). Results. Sixty subjects were evaluated. Using the CMAD model, control subjects had lower median (IQR) alveolar NO than all PAH subjects (2.0 (1.5, 2.5) versus 3.14 ppb (2.3, 4.0), p = 0.008). SSc-ILD had significantly lower median conducting airway NO compared to controls (1009.5 versus 1342.1 ml⁎ppb/s, p = 0.04). SSc-PAH had increased median (IQR) alveolar NO compared to controls (3.3 (3.0, 5.7) versus 2.0 ppb (1.5, 2.5), p = 0.01). SSc-PAH conducting airway NO inversely correlated with DLCO (r −0.88 (95% CI −0.99, −0.26)). Conclusion. We have demonstrated feasibility, identified that CMAD modeling is preferred in SSc, and reported the magnitude of differences across cases and controls. Our data supports discriminative validity of eNO in SSc lung disease. PMID:28293128

  10. 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

  11. 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

  12. 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

  13. Interaction between nitric oxide and prostanoids in the respiratory system.

    PubMed

    Strapkova, A; Antosova, M; Nosalova, G

    2006-01-01

    Prostaglandins and nitric oxide are important mediators of different physiological and pathophysiological processes. So far, is not characterized clearly their relationship in the conditions of airways hyperreactivity. We tried to detect the relationship of interaction NOS-COX in conditions of exogenous irritant-induced experimental bronchial hyperreactivity. Male guinea pigs were used in the experiment. Animals received agent that inhibits COX activity--diclofenac in a dose of 10 mg/kg i.m. or direct NO donor--molsidomine in a dose of 2 mg/kg i.p. Agents were administered singly (10 days) or in combination (last 3 days). Then animals were exposed to the toluene vapours for two hours over each of three consecutive days to provoke hyperreactivity. Then we recorded the reactivity changes to cumulative doses of histamine or acetylcholine (10(-8)-10(-3) mol/I). The administration of NO donor (10 days) and consecutive COX inhibition (3 days) increased the reactivity of both observed preparations in comparison to agents administered single. COX inhibition during 10 days and consecutive treatment with NO donor (3 days) evoked different changes of tracheal smooth muscle and lung tissue smooth muscle response but had more beneficial effect on the airways reactivity on the whole. It is possible to suppose some participation of both followed enzymatic systems and theirs interaction in our experimental conditions since airways reactivity was affected the by used agents (Fig. 7, Ref. 32).

  14. Detection of nitric oxide pollution

    NASA Technical Reports Server (NTRS)

    Chackerian, C., Jr.; Weisbach, M. F.

    1973-01-01

    Studies of absorption spectra enhancement of certain atomic and molecular species inserter in dye-laser cavities have indicated that nitric oxide can be determined at low concentrations. Absorption coefficient of small amounts of nitric oxide in intra-laser-cavity absorption cell containing helium is enhanced by more than two orders of magnitude.

  15. Bacterial nitric oxide synthases.

    PubMed

    Crane, Brian R; Sudhamsu, Jawahar; Patel, Bhumit A

    2010-01-01

    Nitric oxide synthases (NOSs) are multidomain metalloproteins first identified in mammals as being responsible for the synthesis of the wide-spread signaling and protective agent nitric oxide (NO). Over the past 10 years, prokaryotic proteins that are homologous to animal NOSs have been identified and characterized, both in terms of enzymology and biological function. Despite some interesting differences in cofactor utilization and redox partners, the bacterial enzymes are in many ways similar to their mammalian NOS (mNOS) counterparts and, as such, have provided insight into the structural and catalytic properties of the NOS family. In particular, spectroscopic studies of thermostable bacterial NOSs have revealed key oxyheme intermediates involved in the oxidation of substrate L-arginine (Arg) to product NO. The biological functions of some bacterial NOSs have only more recently come to light. These studies disclose new roles for NO in biology, such as taking part in toxin biosynthesis, protection against oxidative stress, and regulation of recovery from radiation damage.

  16. Nitric oxide neurotoxicity.

    PubMed

    Dawson, V L; Dawson, T M

    1996-06-01

    Derangements in glutamate neurotransmission have been implicated in several neurodegenerative disorders including, stroke, epilepsy, Huntington's disease, Alzheimer's disease, and amyotrophic lateral sclerosis (ALS). Activation of the N-methyl-D-aspartate (NMDA) receptor subtype of glutamate receptors results in the influx of calcium which binds calmodulin and activates neuronal nitric oxide synthase (nNOS), to convent L-arginine to citrulline and nitric oxide (NO). NO has many roles in the central nervous system as a messenger molecule, however, when generated in excess NO can be neurotoxic. Excess NO is in part responsible for glutamate neurotoxicity in primary neuronal cell culture and in animal models of stroke. It is likely that most of the neurotoxic actions of NO are mediated by peroxynitrite (ONOO-), the reaction product from NO and superoxide anion. In pathologic conditions, peroxynitrite and oxygen free radicals can be generated in excess of a cell antioxidant capacity resulting in severe damage to cellular constituents including proteins, DNA and lipids. The inherent biochemical and physiological characteristics of the brain, including high lipid concentrations and energy requirements, make it particularly susceptible to free radical and oxidant mediated insult. Increasing evidence indicates that many neurologic disorders may have components of free radical and oxidative stress induced injury.

  17. Development and Analysis of Patient-Based Complete Conducting Airways Models

    PubMed Central

    Bordas, Rafel; Lefevre, Christophe; Veeckmans, Bart; Pitt-Francis, Joe; Fetita, Catalin; Brightling, Christopher E.; Kay, David; Siddiqui, Salman; Burrowes, Kelly S.

    2015-01-01

    The analysis of high-resolution computed tomography (CT) images of the lung is dependent on inter-subject differences in airway geometry. The application of computational models in understanding the significance of these differences has previously been shown to be a useful tool in biomedical research. Studies using image-based geometries alone are limited to the analysis of the central airways, down to generation 6–10, as other airways are not visible on high-resolution CT. However, airways distal to this, often termed the small airways, are known to play a crucial role in common airway diseases such as asthma and chronic obstructive pulmonary disease (COPD). Other studies have incorporated an algorithmic approach to extrapolate CT segmented airways in order to obtain a complete conducting airway tree down to the level of the acinus. These models have typically been used for mechanistic studies, but also have the potential to be used in a patient-specific setting. In the current study, an image analysis and modelling pipeline was developed and applied to a number of healthy (n = 11) and asthmatic (n = 24) CT patient scans to produce complete patient-based airway models to the acinar level (mean terminal generation 15.8 ± 0.47). The resulting models are analysed in terms of morphometric properties and seen to be consistent with previous work. A number of global clinical lung function measures are compared to resistance predictions in the models to assess their suitability for use in a patient-specific setting. We show a significant difference (p < 0.01) in airways resistance at all tested flow rates in complete airway trees built using CT data from severe asthmatics (GINA 3–5) versus healthy subjects. Further, model predictions of airways resistance at all flow rates are shown to correlate with patient forced expiratory volume in one second (FEV1) (Spearman ρ = −0.65, p < 0.001) and, at low flow rates (0.00017 L/s), FEV1 over forced vital capacity (FEV1/FVC

  18. A new removable airway stent

    PubMed Central

    Amundsen, Tore; Sørhaug, Sveinung; Leira, Håkon Olav; Tyvold, Stig Sverre; Langø, Thomas; Hammer, Tommy; Manstad-Hulaas, Frode; Mattsson, Erney

    2016-01-01

    Background Malignant airway obstruction is a feared complication and will most probably occur more frequently in the future because of increasing cancer incidence and increased life expectancy in cancer patients. Minimal invasive treatment using airway stents represents a meaningful and life-saving palliation. We present a new removable airway stent for improved individualised treatment. Methods To our knowledge, the new airway stent is the world's first knitted and uncovered self-expanding metal stent, which can unravel and be completely removed. In an in vivo model using two anaesthetised and spontaneously breathing pigs, we deployed and subsequently removed the stents by unravelling the device. The procedures were executed by flexible bronchoscopy in an acute and a chronic setting – a ‘proof-of-principle’ study. Results The new stent was easily and accurately deployed in the central airways, and it remained fixed in its original position. It was easy to unravel and completely remove from the airways without clinically significant complications. During the presence of the stent in the chronic study, granulation tissue was induced. This tissue disappeared spontaneously with the removal. Conclusions The new removable stent functioned according to its purpose and unravelled easily, and it was completely removed without significant technical or medical complications. Induced granulation tissue disappeared spontaneously. Further studies on animals and humans are needed to define its optimal indications and future use. PMID:27608269

  19. Interleukin-1beta causes pulmonary inflammation, emphysema, and airway remodeling in the adult murine lung.

    PubMed

    Lappalainen, Urpo; Whitsett, Jeffrey A; Wert, Susan E; Tichelaar, Jay W; Bry, Kristina

    2005-04-01

    The production of the inflammatory cytokine interleukin (IL)-1 is increased in lungs of patients with chronic obstructive pulmonary disease (COPD) or asthma. To characterize the in vivo actions of IL-1 in the lung, transgenic mice were generated in which human IL-1beta was expressed in the lung epithelium with a doxycycline-inducible system controlled by the rat Clara cell secretory protein (CCSP) promoter. Induction of IL-1beta expression in the lungs of adult mice caused pulmonary inflammation characterized by neutrophil and macrophage infiltrates. IL-1beta caused distal airspace enlargement, consistent with emphysema. IL-1beta caused disruption of elastin fibers in alveolar septa and fibrosis in airway walls and in the pleura. IL-1beta increased the thickness of conducting airways, enhanced mucin production, and caused lymphocytic aggregates in the airways. Decreased immunostaining for the winged helix transcription factor FOXA2 was associated with goblet cell hyperplasia in IL-1beta-expressing mice. The production of the neutrophil attractant CXC chemokines KC (CXCL1) and MIP-2 (CXCL2), and of matrix metalloproteases MMP-9 and MMP-12, was increased by IL-1beta. Chronic production of IL-1beta in respiratory epithelial cells of adult mice causes lung inflammation, enlargement of distal airspaces, mucus metaplasia, and airway fibrosis in the adult mouse.

  20. Nitric Oxide as a Mediator of Oxidant Lung Injury Due to Paraquat

    NASA Astrophysics Data System (ADS)

    Berisha, Hasan I.; Pakbaz, Hedayatollah; Absood, Afaf; Said, Sami I.

    1994-08-01

    At low concentrations, nitric oxide is a physiological transmitter, but in excessive concentrations it may cause cell and tissue injury. We report that in acute oxidant injury induced by the herbicide paraquat in isolated guinea pig lungs, nitric oxide synthesis was markedly stimulated, as evidenced by increased levels of cyclic GMP in lung perfusate and of nitrite and L-citrulline production in lung tissue. All signs of injury, including increased airway and perfusion pressures, pulmonary edema, and protein leakage into the airspaces, were dose-dependently attenuated or totally prevented by either N^G-nitro-L-arginine methyl ester or N^ω-nitro-L-arginine, selective and competitive inhibitors of nitric oxide synthase. Protection was reversed by excess L-arginine but not by its enantiomer D-arginine. When blood was added to the lung perfusate, the paraquat injury was moderated or delayed as it was when paraquat was given to anesthetized guinea pigs. The rapid onset of injury and its failure to occur in the absence of Ca2+ suggest that constitutive rather than inducible nitric oxide synthase was responsible for the stimulated nitric oxide synthesis. The findings indicate that nitric oxide plays a critical role in the production of lung tissue injury due to paraquat, and it may be a pathogenetic factor in other forms of oxidant tissue injury.

  1. Nasal nitric oxide in children with adenoidal hypertrophy: a preliminary study.

    PubMed

    Torretta, S; Bossi, A; Capaccio, P; Marchisio, P; Esposito, S; Brevi, A; Pignataro, L

    2010-06-01

    Nasal nitric oxide, a mediator involved in upper airway inflammation, is impaired in children with allergic rhinitis and rhinosinusitis. Normal values are 200-450 parts per billion, but no data are available concerning its levels in children with adenoidal obstruction, predisposing to chronic nasosinusal inflammation. This study aimed to: (1) measure nasal nitric oxide levels in non-allergic children with adenoidal hypertrophy and (2) assess its possible relationship with the degree of adenoidal hypertrophy and other variable (gender, age, body max index, passive smoking exposure, recurrent acute otitis media, recurrent respiratory infections, and hypertrophy of nasal turbinates). Eighty-one children with suspected adenoidal hypertrophy underwent nasal fibroendoscopy to assess the degree of adenoidal hypertrophy, and nasal nitric oxide on-line measurements by means of a dedicated chemiluminescence analyser. Nasal nitric oxide was successfully measured in 35 patients, most of whom had levels >450 parts per billion; the values were significantly higher (p=0.031) in children with non-obstructive adenoids. There was no significant correlation with any other variable. Preliminary data show above-normal nasal nitric oxide levels in children with adenoidal hypertrophy, especially those with non-obstructive adenoids. This suggests nitric oxide involvement in recurrent nasopharyngeal inflammation due to adenoidal hypertrophy. Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.

  2. Effects of nitric oxide in mucociliary transport.

    PubMed

    Blanco, Eleonora Elisia Abra; Pinge, Marli Cardoso Martins; Andrade Neto, Otavio André; Pessoa, Nathália Gardin

    2009-01-01

    The airways are made up of ciliated epithelium which secretes mucous, protecting the respiratory tract from particles inhaled during breathing. Its is paramount to understand the physiology and the mechanisms involved in mucociliary activity. Literature suggests that Nitric oxide (NO), especially the one produced by iNOS expression, maintains the mucociliary function and the immune defense of the nasal cavity. to assess NO participation and the enzymatic pathways in the production of NO and mucociliary transport, using constructive and inductive NO synthetase inhibitors, L-NAME and aminoguanidine, respectively. frog palates were prepared and immersed in ringer (control), L-NAME or aminoguanidine solutions. The palates were immersed in these solutions for four periods of 15 minutes. Mucociliary transport measures were carried out before and after each exposure. control palates maintained stable their transportation speed. L-NAME increased, while aminoguanidine reduced mucous transportation velocity. unspecific cNOS block with L-NAME and relatively specific iNOS block with aminoguanidine results leads us to propose that depending on the pathway, the NO can increase or reduce mucociliary transport in frog palates.

  3. Airway Hydration and COPD

    PubMed Central

    Ghosh, Arunava; Boucher, R.C.; Tarran, Robert

    2015-01-01

    Chronic obstructive pulmonary disease (COPD) is one of the prevalent causes of worldwide mortality and encompasses two major clinical phenotypes, i.e., chronic bronchitis (CB) and emphysema. The most common cause of COPD is chronic tobacco inhalation. Research focused on the chronic bronchitic phenotype of COPD has identified several pathological processes that drive disease initiation and progression. For example, the lung’s mucociliary clearance (MCC) system performs the critical task of clearing inhaled pathogens and toxic materials from the lung. MCC efficiency is dependent on: (i) the ability of apical plasma membrane ion channels such as the cystic fibrosis transmembrane conductance regulator (CFTR) and the epithelial Na+ channel (ENaC) to maintain airway hydration; (ii) ciliary beating; and, (iii) appropriate rates of mucin secretion. Each of these components is impaired in CB and likely contributes to the mucus stasis/accumulation seen in CB patients. This review highlights the cellular components responsible for maintaining MCC and how this process is disrupted following tobacco exposure and with CB. We shall also discuss existing therapeutic strategies for the treatment of chronic bronchitis and how components of the MCC can be used as biomarkers for the evaluation of tobacco or tobacco-like-product exposure. PMID:26068443

  4. Upper airway resistance syndrome.

    PubMed

    Montserrat, J M; Badia, J R

    1999-03-01

    This article reviews the clinical picture, diagnosis and management of the upper airway resistance syndrome (UARS). Presently, there is not enough data on key points like the frequency of UARS and the morbidity associated with this condition. Furthermore, the existence of LIARS as an independent sleep disorder and its relation with snoring and obstructive events is in debate. The diagnosis of UARS is still a controversial issue. The technical limitations of the classic approach to monitor airflow with thermistors and inductance plethysmography, as well as the lack of a precise definition of hypopnea, may have led to a misinterpretation of UARS as an independent diagnosis from the sleep apnea/hypopnea syndrome. The diagnosis of this syndrome can be missed using a conventional polysomnographic setting unless appropriate techniques are applied. The use of an esophageal balloon to monitor inspiratory effort is currently the gold standard. However, other sensitive methods such as the use of a pneumotachograph and, more recently, nasal cannula/pressure transducer systems or on-line monitoring of respiratory impedance with the forced oscillation technique may provide other interesting possibilities. Recognition and characterization of this subgroup of patients within sleep breathing disorders is important because they are symptomatic and may benefit from treatment. Management options to treat UARS comprise all those currently available for sleep apnea/hypopnea syndrome (SAHS). However, the subset of patients classically identified as LIARS that exhibit skeletal craneo-facial abnormalities might possibly obtain further benefit from maxillofacial surgery.

  5. 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

  6. Efficacy of Surgical Airway Plasty for Benign Airway Stenosis

    PubMed Central

    Takahama, Makoto; Nakajima, Ryu; Kimura, Michitaka; Inoue, Hidetoshi; Yamamoto, Ryoji

    2015-01-01

    Background: Long-term patency is required during treatment for benign airway stenosis. This study investigated the effectiveness of surgical airway plasty for benign airway stenosis. Methods: Clinical courses of 20 patients, who were treated with surgical plasty for their benign airway stenosis, were retrospectively investigated. Results: Causes of stenosis were tracheobronchial tuberculosis in 12 patients, post-intubation stenosis in five patients, malacia in two patients, and others in one patient. 28 interventional pulmonology procedures and 20 surgical plasty were performed. Five patients with post-intubation stenosis and four patients with tuberculous stenosis were treated with tracheoplasty. Eight patients with tuberculous stenosis were treated with bronchoplasty, and two patients with malacia were treated with stabilization of the membranous portion. Anastomotic stenosis was observed in four patients, and one to four additional treatments were required. Performance status, Hugh–Jones classification, and ventilatory functions were improved after surgical plasty. Outcomes were fair in patients with tuberculous stenosis and malacia. However, efficacy of surgical plasty for post-intubation stenosis was not observed. Conclusion: Surgical airway plasty may be an acceptable treatment for tuberculous stenosis. Patients with malacia recover well after surgical plasty. There may be untreated patients with malacia who have the potential to benefit from surgical plasty. PMID:26567879

  7. Efficacy of Surgical Airway Plasty for Benign Airway Stenosis.

    PubMed

    Tsukioka, Takuma; Takahama, Makoto; Nakajima, Ryu; Kimura, Michitaka; Inoue, Hidetoshi; Yamamoto, Ryoji

    2016-01-01

    Long-term patency is required during treatment for benign airway stenosis. This study investigated the effectiveness of surgical airway plasty for benign airway stenosis. Clinical courses of 20 patients, who were treated with surgical plasty for their benign airway stenosis, were retrospectively investigated. Causes of stenosis were tracheobronchial tuberculosis in 12 patients, post-intubation stenosis in five patients, malacia in two patients, and others in one patient. 28 interventional pulmonology procedures and 20 surgical plasty were performed. Five patients with post-intubation stenosis and four patients with tuberculous stenosis were treated with tracheoplasty. Eight patients with tuberculous stenosis were treated with bronchoplasty, and two patients with malacia were treated with stabilization of the membranous portion. Anastomotic stenosis was observed in four patients, and one to four additional treatments were required. Performance status, Hugh-Jones classification, and ventilatory functions were improved after surgical plasty. Outcomes were fair in patients with tuberculous stenosis and malacia. However, efficacy of surgical plasty for post-intubation stenosis was not observed. Surgical airway plasty may be an acceptable treatment for tuberculous stenosis. Patients with malacia recover well after surgical plasty. There may be untreated patients with malacia who have the potential to benefit from surgical plasty.

  8. An Official ATS Clinical Practice Guideline: Interpretation of Exhaled Nitric Oxide Levels (FeNO) for Clinical Applications

    PubMed Central

    Dweik, Raed A.; Boggs, Peter B.; Erzurum, Serpil C.; Irvin, Charles G.; Leigh, Margaret W.; Lundberg, Jon O.; Olin, Anna-Carin; Plummer, Alan L.; Taylor, D. Robin

    2011-01-01

    Background: Measurement of fractional nitric oxide (NO) concentration in exhaled breath (FeNO) is a quantitative, noninvasive, simple, and safe method of measuring airway inflammation that provides a complementary tool to other ways of assessing airways disease, including asthma. While FeNO measurement has been standardized, there is currently no reference guideline for practicing health care providers to guide them in the appropriate use and interpretation of FeNO in clinical practice. Purpose: To develop evidence-based guidelines for the interpretation of FeNO measurements that incorporate evidence that has accumulated over the past decade. Methods: We created a multidisciplinary committee with expertise in the clinical care, clinical science, or basic science of airway disease and/or NO. The committee identified important clinical questions, synthesized the evidence, and formulated recommendations. Recommendations were developed using pragmatic systematic reviews of the literature and the GRADE approach. Results: The evidence related to the use of FeNO measurements is reviewed and clinical practice recommendations are provided. Conclusions: In the setting of chronic inflammatory airway disease including asthma, conventional tests such as FEV1 reversibility or provocation tests are only indirectly associated with airway inflammation. FeNO offers added advantages for patient care including, but not limited to (1) detecting of eosinophilic airway inflammation, (2) determining the likelihood of corticosteroid responsiveness, (3) monitoring of airway inflammation to determine the potential need for corticosteroid, and (4) unmasking of otherwise unsuspected nonadherence to corticosteroid therapy. PMID:21885636

  9. Demystified … Nitric oxide

    PubMed Central

    Stuart-Smith, K

    2002-01-01

    The discovery of nitric oxide (NO) demonstrated that cells could communicate via the manufacture and local diffusion of an unstable lipid soluble molecule. Since the original demonstration of the vascular relaxant properties of endothelium derived NO, this fascinating molecule has been shown to have multiple, complex roles within many biological systems. This review cannot hope to cover all of the recent advances in NO biology, but seeks to place the discovery of NO in its historical context, and show how far our understanding has come in the past 20 years. The role of NO in mitochondrial respiration, and consequently in oxidative stress, is described in detail because these processes probably underline the importance of NO in the development of disease. PMID:12456772

  10. Nitric oxide enhancement strategies.

    PubMed

    Bryan, Nathan S

    2015-08-01

    It is becoming increasingly clear that many diseases are characterized or associated with perturbations in nitric oxide (NO) production/signaling. Therapeutics or strategies designed to restore normal NO homeostasis will likely have broad application and utility. This highly complex and multistep pathway for NO production and subsequent target activation provides many steps in the endogenous pathway that may be useful targets for drug development for cardiovascular disease, antimicrobial, cancer, wound healing, etc. This article will summarize known strategies that are currently available or in development for enhancing NO production or availability in the human body. Each strategy will be discussed including exogenous sources of NO, use of precursors to promote NO production and downstream pathways affected by NO production with advantages and disadvantages highlighted for each. Development of NO-based therapeutics is and will continue to be a major focus of biotech, academia as well as pharmaceutical companies. Application of safe and effective strategies will certainly transform health and disease.

  11. Bronchoscopic management of malignant airway obstruction.

    PubMed

    Mitchell, Patrick D; Kennedy, Marcus P

    2014-05-01

    Approximately one-third of patients with lung cancer will develop airway obstruction and many cancers lead to airway obstruction through meta stases. The treatment of malignant airway obstruction is often a multimodality approach and is usually performed for palliation of symptoms in advanced lung cancer. Removal of airway obstruction is associated with improvement in symptoms, quality of life, and lung function. Patient selection should exclude patients with short life expectancy, limited symptoms, and an inability to visualize beyond the obstruction. This review outlines both the immediate and delayed bronchoscopic effect options for the removal of airway obstruction and preservation of airway patency with endobronchial stenting.

  12. Mitochondrial Dysfunction in Airway Disease.

    PubMed

    Prakash, Y S; Pabelick, Christina M; Sieck, Gary C

    2017-09-01

    There is increasing appreciation that mitochondria serve cellular functions beyond oxygen sensing and energy production. Accordingly, it has become important to explore noncanonical roles of mitochondria in normal and pathophysiological processes that influence airway structure and function in the context of diseases such as asthma and COPD. Mitochondria can sense upstream processes such as inflammation, infection, tobacco smoke, and environmental insults important in these diseases and in turn can respond to such stimuli through altered mitochondrial protein expression, structure, and resultant dysfunction. Conversely, mitochondrial dysfunction has downstream influences on cytosolic and mitochondrial calcium regulation, airway contractility, gene and protein housekeeping, responses to oxidative stress, proliferation, apoptosis, fibrosis, and certainly metabolism, which are all key aspects of airway disease pathophysiology. Indeed, mitochondrial dysfunction is thought to play a role even in normal processes such as aging and senescence and in conditions such as obesity, which impact airway diseases. Thus, understanding how mitochondrial structure and function play central roles in airway disease may be critical for the development of novel therapeutic avenues targeting dysfunctional mitochondria. In this case, it is likely that mitochondria of airway epithelium, smooth muscle, and fibroblasts play differential roles, consistent with their contributions to disease biology, underlining the challenge of targeting a ubiquitous cellular element of existential importance. This translational review summarizes the current state of understanding of mitochondrial processes that play a role in airway disease pathophysiology and identifying areas of unmet research need and opportunities for novel therapeutic strategies. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  13. Airway management in emergency situations.

    PubMed

    Dörges, Volker

    2005-12-01

    Securing and monitoring the airway are among the key requirements of appropriate therapy in emergency patients. Failures to secure the airways can drastically increase morbidity and mortality of patients within a very short time. Therefore, the entire range of measures needed to secure the airway in an emergency, without intermediate ventilation and oxygenation, is limited to 30-40 seconds. Endotracheal intubation is often called the 'gold standard' for airway management in an emergency, but multiple failed intubation attempts do not result in maintaining oxygenation; instead, they endanger the patient by prolonging hypoxia and causing additional trauma to the upper airways. Thus, knowledge and availability of alternative procedures are also essential in every emergency setting. Given the great variety of techniques available, it is important to establish a well-planned, methodical protocol within the framework of an algorithm. This not only facilitates the preparation of equipment and the training of personnel, it also ensures efficient decision-making under time pressure. Most anaesthesia-related deaths are due to hypoxaemia when difficulty in securing the airway is encountered, especially in obstetrics during induction of anaesthesia for caesarean delivery. The most commonly occurring adverse respiratory events are failure to intubate, failure to recognize oesophageal intubation, and failure to ventilate. Thus, it is essential that every anaesthesiologist working on the labour and delivery ward is comfortable with the algorithm for the management of failed intubation. The algorithm for emergency airway management describing the sequence of various procedures has to be adapted to internal standards and to techniques that are available.

  14. Distal realignment (tibial tuberosity transfer).

    PubMed

    Feller, Julian Ashley

    2012-09-01

    Although tibial tuberosity (TT) transfer has for many years been the basis of many protocols for the management of patellar instability, the role of pure medial transfer in particular appears to be declining. In contrast, the greater recognition of the importance of patella alta as a predisposing factor to recurrent patellar dislocation has resulted in a resurgence in the popularity of distal TT transfer. When TT transfer is performed, the direction and amount of transfer is based on the patellar height and the lateralization of the TT relative to the trochlear groove. Patellar height is best assessed on a lateral radiograph with the knee in flexion using a ratio that uses the articular surface of the patella in relation to the height above the tibia. Assessment of lateralization of the TT relative to the trochlear groove can be made using either computed tomography or magnetic resonance imaging scans.

  15. Expression of nitric oxide synthases in leukocytes in nasal polyps.

    PubMed

    Yoshimura, Tsuyoshi; Moon, Tae Chul; St Laurent, Chris D; Puttagunta, Lakshmi; Chung, Kerri; Wright, Erin; Yoshikawa, Mamoru; Moriyama, Hiroshi; Befus, A Dean

    2012-03-01

    Nitric oxide (NO) has various roles in airway physiology and pathophysiology. Monitoring exhaled NO levels is increasingly common to measure airways inflammation and inhaled NO studied for its therapeutic value in premature infants and adult respiratory distress syndrome. NO is produced by 3 isoforms of NO synthase (NOS1, 2, 3), and each can play distinct and perhaps overlapping roles in the airways. However, the distribution, regulation, and functions of NOS in various cells in the upper airways, particularly in leukocytes, are incompletely understood. To characterize the expression of NOS isoforms in leukocytes in normal middle turbinate tissues (MT) and in inflammatory nasal tissue (nasal polyps, NP). Normal MT tissue was collected from surgical specimens that were to be discarded. The NP samples were from surgical tissue archives of 15 patients with chronic rhinosinusitis. Isoforms of NOS in cells were identified by double immunostaining using NOS isoform-specific and leukocyte-specific (mast cell, eosinophil, macrophage, neutrophil, or T cell) antibodies. The proportion of total cells below the epithelium that were positive for each isoform of NOS was higher in NP than in MT. Each isoform of NOS was found in all leukocyte populations studied, and there were significant differences in the percentage of leukocytes expressing NOS isoforms between MT and NP. All isoforms of NOS are expressed in leukocytes in MT and NP, and their expression varies among leukocyte types. Our data provide a basis to investigate the regulation, cell distribution, and distinct functions of NOS isoforms in normal and inflamed nasal tissues. Copyright © 2012 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  16. Nitric oxide signaling in plants.

    PubMed

    Shapiro, Allan D

    2005-01-01

    Plants have four nitric oxide synthase (NOS) enzymes. NOS1 appears mitochondrial, and inducible nitric oxide synthase (iNOS) chloroplastic. Distinct peroxisomal and apoplastic NOS enzymes are predicted. Nitrite-dependent NO synthesis is catalyzed by cytoplasmic nitrate reductase or a root plasma membrane enzyme, or occurs nonenzymatically. Nitric oxide undergoes both catalyzed and uncatalyzed oxidation. However, there is no evidence of reaction with superoxide, and S-nitrosylation reactions are unlikely except during hypoxia. The only proven direct targets of NO in plants are metalloenzymes and one metal complex. Nitric oxide inhibits apoplastic catalases/ascorbate peroxidases in some species but may stimulate these enzymes in others. Plants also have the NO response pathway involving cGMP, cADPR, and release of calcium from internal stores. Other known targets include chloroplast and mitochondrial electron transport. Nitric oxide suppresses Fenton chemistry by interacting with ferryl ion, preventing generation of hydroxyl radicals. Functions of NO in plant development, response to biotic and abiotic stressors, iron homeostasis, and regulation of respiration and photosynthesis may all be ascribed to interaction with one of these targets. Nitric oxide function in drought/abscisic acid (ABA)-induction of stomatal closure requires nitrate reductase and NOS1. Nitric oxide synthasel likely functions to produce sufficient NO to inhibit photosynthetic electron transport, allowing nitrite accumulation. Nitric oxide is produced during the hypersensitive response outside cells undergoing programmed cell death immediately prior to loss of plasma membrane integrity. A plasma membrane lipid-derived signal likely activates apoplastic NOS. Nitric oxide diffuses within the apoplast and signals neighboring cells via hydrogen peroxide (H2O2)-dependent induction of salicylic acid biosynthesis. Response to wounding appears to involve the same NOS and direct targets.

  17. Exogenous irritant-induced airway hyperreactivity and inhibition of soluble guanylyl cyclase.

    PubMed

    Antosová, Martina; Strapková, Anna; Turcan, Tomás

    2008-10-01

    The majority of nitric oxide (NO) effects in the respiratory system are caused by stimulation of soluble guanylyl cyclase (sGC) with subsequent increase of cyclic guanosine monophosphate (cGMP) production. The importance of this mechanism of NO action in airway hyperreactivity (AHR) pathogenesis is unknown. Therefore, the aim of our experiment was to examine the changes of airway reactivity enhanced by toluene vapor exposure in the presence or inhibition of sGC activity in guinea pigs. Animals were treated with a nonspecific sGC inhibitor, methylene blue, in a dose of 50 or 100 mg/kg body weight, administered by intraperitoneal injection 30 min before or after exposure to toluene vapors. The toluene exposure lasted 2 hr in each of 3 consecutive days under in vivo conditions. Thereafter, the tracheal and lung tissue smooth muscle response to cumulative doses of mediators (histamine or acetylcholine) was recorded under in vitro conditions. The exposure to toluene vapors significantly increased the airway reactivity to both mediators in comparison with the healthy animal group. The administration of methylene blue decreased the amplitude of airway smooth muscle contraction in toluene-induced hyperreactivity. The decreases were dependent on the inhibitor doses, on a regimen of administration (before or after toluene inhalation), the level of the respiratory system (trachea, lung), and the bronchoconstrictor mediators. Our results suggest that the interaction between NO and sGC may be important for airway reactivity changes, but other mechanisms of NO action are important in AHR pathogenesis, too.

  18. Nitric oxide and cardiovascular system.

    PubMed

    Cengel, Atiye; Sahinarslan, Asife

    2006-12-01

    Endothelium has many important functions including the control of blood-tissue permeability and vascular tonus, regulation of vascular surface properties for homeostasis and inflammation. Nitric oxide is the chief molecule in regulation of endothelial functions. Nitric oxide deficiency, which is also known as endothelial dysfunction, is the first step for the occurrence of many disease states in cardiovascular system including heart failure, hypertension, dyslipidemia, insulin resistance, diabetes mellitus, hyperhomocysteinemia and smoking. This review deals with the importance of nitric oxide for cardiovascular system. It also includes the latest improvements in the diagnosis and treatment of endothelial dysfunction.

  19. 49 CFR 173.337 - Nitric oxide.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 2 2013-10-01 2013-10-01 false Nitric oxide. 173.337 Section 173.337... SHIPMENTS AND PACKAGINGS Gases; Preparation and Packaging § 173.337 Nitric oxide. (a) Nitric oxide must be... valve and valve seat that will not deteriorate in contact with nitric oxide. Cylinders or valves may...

  20. 49 CFR 173.337 - Nitric oxide.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 2 2014-10-01 2014-10-01 false Nitric oxide. 173.337 Section 173.337... SHIPMENTS AND PACKAGINGS Gases; Preparation and Packaging § 173.337 Nitric oxide. (a) Nitric oxide must be... valve and valve seat that will not deteriorate in contact with nitric oxide. Cylinders or valves may...

  1. 49 CFR 173.337 - Nitric oxide.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 2 2011-10-01 2011-10-01 false Nitric oxide. 173.337 Section 173.337... SHIPMENTS AND PACKAGINGS Gases; Preparation and Packaging § 173.337 Nitric oxide. (a) Nitric oxide must be... valve and valve seat that will not deteriorate in contact with nitric oxide. Cylinders or valves may...

  2. 49 CFR 173.337 - Nitric oxide.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 2 2012-10-01 2012-10-01 false Nitric oxide. 173.337 Section 173.337... SHIPMENTS AND PACKAGINGS Gases; Preparation and Packaging § 173.337 Nitric oxide. (a) Nitric oxide must be... valve and valve seat that will not deteriorate in contact with nitric oxide. Cylinders or valves may...

  3. 49 CFR 173.158 - Nitric acid.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 2 2012-10-01 2012-10-01 false Nitric acid. 173.158 Section 173.158... Nitric acid. (a) Nitric acid exceeding 40 percent concentration may not be packaged with any other material. (b) Nitric acid in any concentration which does not contain sulfuric acid or hydrochloric acid as...

  4. 49 CFR 173.158 - Nitric acid.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 2 2010-10-01 2010-10-01 false Nitric acid. 173.158 Section 173.158... Nitric acid. (a) Nitric acid exceeding 40 percent concentration may not be packaged with any other material. (b) Nitric acid in any concentration which does not contain sulfuric acid or hydrochloric acid as...

  5. 49 CFR 173.158 - Nitric acid.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 2 2014-10-01 2014-10-01 false Nitric acid. 173.158 Section 173.158... Nitric acid. (a) Nitric acid exceeding 40 percent concentration may not be packaged with any other material. (b) Nitric acid in any concentration which does not contain sulfuric acid or hydrochloric acid as...

  6. 49 CFR 173.158 - Nitric acid.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 2 2013-10-01 2013-10-01 false Nitric acid. 173.158 Section 173.158... Nitric acid. (a) Nitric acid exceeding 40 percent concentration may not be packaged with any other material. (b) Nitric acid in any concentration which does not contain sulfuric acid or hydrochloric acid as...

  7. 49 CFR 173.158 - Nitric acid.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 2 2011-10-01 2011-10-01 false Nitric acid. 173.158 Section 173.158... Nitric acid. (a) Nitric acid exceeding 40 percent concentration may not be packaged with any other material. (b) Nitric acid in any concentration which does not contain sulfuric acid or hydrochloric acid as...

  8. 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

  9. Deterioration of epithelium mediated mechanisms in diabetic-antigen sensitized airways of guinea pigs.

    PubMed

    Bano, Saidullah; Swati, Omanwar; Kambadur, Muralidhar; Mohammad, Fahim

    2016-01-01

    The onset of diabetes causes disruption of respiratory epithelial mediators. The present study investigates whether diabetes modifies the epithelium mediated bronchial responses in hyper-reactive airway smooth muscle (ASM) primarily through nitric oxide (NO), cyclooxygenase (COX), and epithelium derived hyperpolarizing factor (EpDHF) pathways. Experimental model of guinea pigs having hyper-reactive airways with or without diabetes were developed. The responses of tracheal rings to cumulative concentrations of acetylcholine (ACh) and isoproterenol (IP) in the presence and absence of epithelium and before and after incubation with NO, K(+)ATP and COX inhibitors, N-(ω)-Nitro-L-arginine methyl ester (L-NAME; 100 μM), glybenclamide (10 μM) and indomethacin (100 μM) were assessed. In diabetic guinea pigs with hyper-reactive airways, a decrease in ACh induced bronchoconstriction was observed after epithelium removal and after incubation with L-NAME/indomethacin, suggesting damage to NO/COX pathways. Hyper-reactivity did not alter the response of trachea to ACh but affected the response to IP which was further reduced in hyper-reactive animals with diabetes. The ASM response to IP after glybenclamide treatment did not alter in hyper-reactive guinea pigs and diabetic guinea pigs with hyper-reactive airways, suggesting damage to the EpDHF pathway. Treatment with indomethacin reduced IP response in the hyper-reactive model, and did not produce any change in diabetic model with hyper-reactive airways, indicating further disruption of the COX pathway. EpDHF pathway is damaged in hyper-reactive guinea pigs and in diabetic guinea pigs with hyper-reactive airways. Diabetes further aggravates the NO and COX mediated pathways in diabetic guinea pigs with hyper-reactive airways.

  10. Lung sound analysis helps localize airway inflammation in patients with bronchial asthma

    PubMed Central

    Shimoda, Terufumi; Obase, Yasushi; Nagasaka, Yukio; Nakano, Hiroshi; Ishimatsu, Akiko; Kishikawa, Reiko; Iwanaga, Tomoaki

    2017-01-01

    Purpose Airway inflammation can be detected by lung sound analysis (LSA) at a single point in the posterior lower lung field. We performed LSA at 7 points to examine whether the technique could identify the location of airway inflammation in patients with asthma. Patients and methods Breath sounds were recorded at 7 points on the body surface of 22 asthmatic subjects. Inspiration sound pressure level (ISPL), expiration sound pressure level (ESPL), and the expiration-to-inspiration sound pressure ratio (E/I) were calculated in 6 frequency bands. The data were analyzed for potential correlation with spirometry, airway hyperresponsiveness (PC20), and fractional exhaled nitric oxide (FeNO). Results The E/I data in the frequency range of 100–400 Hz (E/I low frequency [LF], E/I mid frequency [MF]) were better correlated with the spirometry, PC20, and FeNO values than were the ISPL or ESPL data. The left anterior chest and left posterior lower recording positions were associated with the best correlations (forced expiratory volume in 1 second/forced vital capacity: r=−0.55 and r=−0.58; logPC20: r=−0.46 and r=−0.45; and FeNO: r=0.42 and r=0.46, respectively). The majority of asthmatic subjects with FeNO ≥70 ppb exhibited high E/I MF levels in all lung fields (excluding the trachea) and V50%pred <80%, suggesting inflammation throughout the airway. Asthmatic subjects with FeNO <70 ppb showed high or low E/I MF levels depending on the recording position, indicating uneven airway inflammation. Conclusion E/I LF and E/I MF are more useful LSA parameters for evaluating airway inflammation in bronchial asthma; 7-point lung sound recordings could be used to identify sites of local airway inflammation. PMID:28392708

  11. Cystic Fibrosis Transmembrane Conductance Regulator in Sarcoplasmic Reticulum of Airway Smooth Muscle. Implications for Airway Contractility

    PubMed Central

    Cook, Daniel P.; Rector, Michael V.; Bouzek, Drake C.; Michalski, Andrew S.; Gansemer, Nicholas D.; Reznikov, Leah R.; Li, Xiaopeng; Stroik, Mallory R.; Ostedgaard, Lynda S.; Abou Alaiwa, Mahmoud H.; Thompson, Michael A.; Prakash, Y. S.; Krishnan, Ramaswamy; Meyerholz, David K.; Seow, Chun Y.

    2016-01-01

    Rationale: An asthma-like airway phenotype has been described in people with cystic fibrosis (CF). Whether these findings are directly caused by loss of CF transmembrane conductance regulator (CFTR) function or secondary to chronic airway infection and/or inflammation has been difficult to determine. Objectives: Airway contractility is primarily determined by airway smooth muscle. We tested the hypothesis that CFTR is expressed in airway smooth muscle and directly affects airway smooth muscle contractility. Methods: Newborn pigs, both wild type and with CF (before the onset of airway infection and inflammation), were used in this study. High-resolution immunofluorescence was used to identify the subcellular localization of CFTR in airway smooth muscle. Airway smooth muscle function was determined with tissue myography, intracellular calcium measurements, and regulatory myosin light chain phosphorylation status. Precision-cut lung slices were used to investigate the therapeutic potential of CFTR modulation on airway reactivity. Measurements and Main Results: We found that CFTR localizes to the sarcoplasmic reticulum compartment of airway smooth muscle and regulates airway smooth muscle tone. Loss of CFTR function led to delayed calcium reuptake following cholinergic stimulation and increased myosin light chain phosphorylation. CFTR potentiation with ivacaftor decreased airway reactivity in precision-cut lung slices following cholinergic stimulation. Conclusions: Loss of CFTR alters porcine airway smooth muscle function and may contribute to the airflow obstruction phenotype observed in human CF. Airway smooth muscle CFTR may represent a therapeutic target in CF and other diseases of airway narrowing. PMID:26488271

  12. DOES BRACHIAL ARTERY FMD PROVIDE A BIOASSAY FOR NITRIC OXIDE?

    PubMed Central

    Wray, D. Walter; Witman, Melissa A. H.; Ives, Stephen J.; McDaniel, John; Trinity, Joel D.; Conklin, Jamie D.; Supiano, Mark A.; Richardson, Russell S.

    2013-01-01

    This study sought to better define the role of nitric oxide (NO) in brachial artery flow-mediated vasodilation (FMD) in young, healthy humans. Brachial artery blood velocity and diameter were determined (ultrasound Doppler) in eight volunteers (26 ± 1 yrs) before and after 5-min forearm circulatory occlusion with and without intra-arterial infusion of the endothelial nitric oxide synthase (eNOS) inhibitor L-NMMA (0.48 mg/dl/min). Control (CON) and L-NMMA trials were performed with the occlusion cuff placed in the traditional distal position, as well as proximal to the measurement site. FMD was significantly reduced, but not abolished, by L-NMMA in the distal cuff trial (8.9 ± 1.3 to 6.0 ± 0.7%, CON vs. L-NMMA, P = 0.02), with no effect of L-NMMA on FMD with proximal cuff placement (10.6 ± 1.2 to 12.4 ± 1.7%, CON vs. L-NMMA, P = 0.39). When the reduction in shear stimulus following L-NMMA was taken into account, no drug difference was observed for either distal (0.26 ± 0.02 to 0.23 ± 0.03, CON vs. L-NMMA, P = 0.40) or proximal (0.23 ± 0.08 to 0.23 ± 0.03, CON vs. L-NMMA, P = 0.89) FMD trials. These findings challenge the assertion that NO is obligatory for brachial artery FMD, and call into question the sensitivity of this procedure for non-invasive determination of NO bioavailability in young, healthy humans. PMID:23774225

  13. 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

  14. The Id2+ distal tip lung epithelium contains individual multipotent embryonic progenitor cells.

    PubMed

    Rawlins, Emma L; Clark, Cheryl P; Xue, Yan; Hogan, Brigid L M

    2009-11-01

    The conducting airways (bronchi and bronchioles) and peripheral gas exchange (alveolar) regions of the mammalian lung are generated by a process of branching morphogenesis. Evidence suggests that during embryonic development, the undifferentiated epithelial progenitors are located at the distal tips of the branching epithelium. To test this hypothesis, we used an Id2-CreER(T2) knock-in mouse strain to lineage trace the distal epithelial tip cells during either the pseudoglandular or canalicular phases of development. During the pseudoglandular stage, the tip cells both self-renew and contribute descendents to all epithelial cell lineages, including neuroendocrine cells. In addition, individual Id2(+) tip cells can self-renew and contribute descendents to both the bronchiolar and alveolar compartments. By contrast, during the later canalicular stage, the distal epithelial tip cells only contribute descendents to the alveoli. Taken together, this evidence supports a model in which the distal tip of the developing lung contains a multipotent epithelial population, the fate of which changes during development.

  15. [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.

  16. Robotic distal pancreatectomy: a valid option?

    PubMed

    Jung, M K; Buchs, N C; Azagury, D E; Hagen, M E; Morel, P

    2013-10-01

    Although reported in the literature, conventional laparoscopic approach for distal pancreatectomy is still lacking widespread acceptance. This might be due to two-dimensional vision and decreased range of motion to reach and safely dissect this highly vascularized retroperitoneal organ by laparoscopy. However, interest in minimally invasive access is growing ever since and the robotic system could certainly help overcome limitations of the laparoscopic approach in the challenging domain of pancreatic resection, notably in distal pancreatectomy. Robotic distal pancreatectomy with and without spleen preservation has been reported with encouraging outcomes for benign and borderline malignant disease. As a result of upgraded endowristed manipulation and three-dimensional visualization, improved outcome might be expected with the launch of the robotic system in the procedure of distal pancreatectomy. Our aim was thus to extensively review the current literature of robot-assisted surgery for distal pancreatectomy and to evaluate advantages and possible limitations of the robotic approach.

  17. Airway and ventilation management during repair of a large acquired tracheoesophageal fistula: the novel use of a readily available tool.

    PubMed

    Malik, Asif M; Ahmed, Zulfiqar; Durgham, Nasser; Stockmann, Paul T; Belenky, Walter M; Zestos, Maria

    2012-03-01

    Acquired tracheoesophageal fistula (TEF) is a life-threatening disorder of the airway that requires early diagnosis and treatment. The case of an infant who had delayed development of a TEF following endoscopic removal of a disc battery lodged in the midesophagus is reported. A repeat bronchoscopy, performed for respiratory distress 4 days later, showed a large defect in the posterior wall of the distal trachea, including the carina. A Foley catheter was used for airway management in the repair of the acquired TEF.

  18. Nitric oxide transport in an axisymmetric stenosis.

    PubMed

    Liu, Xiao; Fan, Yubo; Xu, X Yun; Deng, Xiaoyan

    2012-10-07

    To test the hypothesis that disturbed flow can impede the transport of nitric oxide (NO) in the artery and hence induce atherogenesis, we used a lumen-wall model of an idealized arterial stenosis with NO produced at the blood vessel-wall interface to study the transport of NO in the stenosis. Blood flows in the lumen and through the arterial wall were simulated by Navier-Stokes equations and Darcy's Law, respectively. Meanwhile, the transport of NO in the lumen and the transport of NO within the arterial wall were modelled by advection-diffusion reaction equations. Coupling of fluid dynamics at the endothelium was achieved by the Kedem-Katchalsky equations. The results showed that both the hydraulic conductivity of the endothelium and the non-Newtonian viscous behaviour of blood had little effect on the distribution of NO. However, the blood flow rate, stenosis severity, red blood cells (RBCs), RBC-free layer and NO production rate at the blood vessel-wall interface could significantly affect the transport of NO. The theoretical study revealed that the transport of NO was significantly hindered in the disturbed flow region distal to the stenosis. The reduced NO concentration in the disturbed flow region might play an important role in the localized genesis and development of atherosclerosis.

  19. Nitric oxide transport in an axisymmetric stenosis

    PubMed Central

    Liu, Xiao; Fan, Yubo; Xu, X. Yun; Deng, Xiaoyan

    2012-01-01

    To test the hypothesis that disturbed flow can impede the transport of nitric oxide (NO) in the artery and hence induce atherogenesis, we used a lumen–wall model of an idealized arterial stenosis with NO produced at the blood vessel–wall interface to study the transport of NO in the stenosis. Blood flows in the lumen and through the arterial wall were simulated by Navier–Stokes equations and Darcy's Law, respectively. Meanwhile, the transport of NO in the lumen and the transport of NO within the arterial wall were modelled by advection–diffusion reaction equations. Coupling of fluid dynamics at the endothelium was achieved by the Kedem–Katchalsky equations. The results showed that both the hydraulic conductivity of the endothelium and the non-Newtonian viscous behaviour of blood had little effect on the distribution of NO. However, the blood flow rate, stenosis severity, red blood cells (RBCs), RBC-free layer and NO production rate at the blood vessel–wall interface could significantly affect the transport of NO. The theoretical study revealed that the transport of NO was significantly hindered in the disturbed flow region distal to the stenosis. The reduced NO concentration in the disturbed flow region might play an important role in the localized genesis and development of atherosclerosis. PMID:22593099

  20. Airway management in the hospital environment.

    PubMed

    Higginson, Ray; Parry, Andy; Williams, Meirion

    In the hospital environment, patients can deteriorate rapidly and for many different reasons. Maintaining a patient's breathing is the main priority in any emergency situation, although achieving airway control can be difficult. All health professionals need to be able to undertake airway management safely. The key is a thorough assessment to ensure first of all whether the airway is patent (open and clear) or not. This article will discuss airway management, both acute and chronic, as well as associated nursing care.

  1. Mechanotransduction, asthma, and airway smooth muscle

    PubMed Central

    Fabry, Ben; Fredberg, Jeffrey J.

    2008-01-01

    Excessive force generation by airway smooth muscle is the main culprit in excessive airway narrowing during an asthma attack. The maximum force the airway smooth muscle can generate is exquisitely sensitive to muscle length fluctuations during breathing, and is governed by complex mechanotransduction events that can best be studied by a hybrid approach in which the airway wall is modeled in silico so as to set a dynamic muscle load comparable to that experienced in vivo. PMID:18836522

  2. Evaluation of nitrogen dioxide scavengers during delivery of inhaled nitric oxide.

    PubMed

    Lindberg, L; Rydgren, G

    1998-09-01

    We have analysed the ability of three nitrogen dioxide absorbing materials (soda lime, noXon and zeolite) to act as nitrogen dioxide scavengers during delivery of inhaled nitric oxide. Different mixtures of gas were produced in a ventilator (Servo Ventilator 300) and passed through an inspiratory tube. Concentrations of nitrogen dioxide and nitric oxide were measured in the distal part of the tube, with and without the gas having passed through a canister containing the different filter materials. Our findings indicated that nitrogen dioxide was absorbed effectively by all filter materials but that there was re-formation of nitrogen dioxide from nitric oxide and oxygen in or immediately after the canister. This initial production of nitrogen dioxide was very rapid and could not be prevented by the use of scavengers. Thus soda lime and zeolite had no practical effect as scavengers in this delivery system, and the effect of noXon was very slight.

  3. Debris buster is a Drosophila scavenger receptor essential for airway physiology.

    PubMed

    Wingen, Almut; Carrera, Pilar; Ekaterini Psathaki, Olympia; Voelzmann, André; Paululat, Achim; Hoch, Michael

    2017-10-01

    Scavenger receptors class B (SR-B) are multifunctional transmembrane proteins, which in vertebrates participate in lipid transport, pathogen clearance, lysosomal delivery and intracellular sorting. Drosophila has 14 SR-B members whose functions are still largely unknown. Here, we reveal a novel role for the SR-B family member Debris buster (Dsb) in Drosophila airway physiology. Larvae lacking dsb show yeast avoidance behavior, hypoxia, and severe growth defects associated with impaired elongation and integrity along the airways. Furthermore, in dsb mutant embryos, the barrier function of the posterior spiracles, which are critical for gas exchange, is not properly established and liquid clearance is locally impaired at the spiracular lumen. We found that Dsb is specifically expressed in a group of distal epithelial cells of the posterior spiracle organ and not throughout the entire airways. Furthermore, tissue-specific knockdown and rescue experiments demonstrate that Dsb function in the airways is only required in the posterior spiracles. Dsb localizes in intracellular vesicles, and a subset of these associate with lysosomes. However, we found that depletion of proteins involved in vesicular transport to the apical membrane, but not in lysosomal function, causes dsb-like airway elongation defects. We propose a model in which Dsb sorts components of the apical extracellular matrix which are essential for airway physiology. Since SR-B LIMP2-deficient mice show reduced expression of several apical plasma membrane proteins, sorting of proteins to the apical membrane is likely an evolutionary conserved function of Dsb and LIMP2. Our data provide insights into a spatially confined function of the SR-B Dsb in intracellular trafficking critical for the physiology of the whole tubular airway network. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. 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.

  5. Comments to Role of upper airway ultrasound in airway management.

    PubMed

    Lien, Wan-Ching

    2017-01-01

    Tracheal ultrasound can be an alternative diagnostic tool in airway management, besides traditional confirmatory methods such as capnography and auscultation. The standard image is a hyperechoic air-mucosa (A-M) interface with a reverberation artifact posteriorly (comet-tail artifact). If the second A-M interface appears, which we call a "double-tract sign," esophageal intubation is considered.

  6. Nitric oxide and cancer

    PubMed Central

    Muntané, Jordi; la Mata, Manuel De

    2010-01-01

    Nitric oxide (NO) is a lipophilic, highly diffusible and short-lived physiological messenger which regulates a variety of important physiological responses including vasodilation, respiration, cell migration, immune response and apoptosis. NO is synthesized by three differentially gene-encoded NO synthase (NOS) in mammals: neuronal NOS (nNOS or NOS-1), inducible NOS (iNOS or NOS-2) and endothelial NOS (eNOS or NOS-3). All isoforms of NOS catalyze the reaction of L-arginine, NADPH and oxygen to NO, L-citrulline and NADP. NO may exert its cellular action by cGMP-dependent as well as by cGMP-independent pathways including postranslational modifications in cysteine (S-nitrosylation or S-nitrosation) and tyrosine (nitration) residues, mixed disulfide formation (S-nitrosoglutathione or GSNO) or promoting further oxidation protein stages which have been related to altered protein function and gene transcription, genotoxic lesions, alteration of cell-cycle check points, apoptosis and DNA repair. NO sensitizes tumor cells to chemotherapeutic compounds. The expression of NOS-2 and NOS-3 has been found to be increased in a variety of human cancers. The multiple actions of NO in the tumor environment is related to heterogeneous cell responses with particular attention in the regulation of the stress response mediated by the hypoxia inducible factor-1 and p53 generally leading to growth arrest, apoptosis or adaptation. PMID:21161018

  7. Nitric oxide in shock.

    PubMed

    Cauwels, A

    2007-09-01

    Refractory hypotension with end-organ hypoperfusion and failure is an ominous feature of shock. Distributive shock is caused by severe infections (septic shock) or severe systemic allergic reactions (anaphylactic shock). In 1986, it was concluded that nitric oxide (NO) is the endothelium-derived relaxing factor that had been discovered 6 years earlier. Since then, NO has been shown to be important for the physiological and pathological control of vascular tone. Nevertheless, although inhibition of NO synthesis restores blood pressure, NO synthase (NOS) inhibition cannot improve outcome, on the contrary. This implies that NO acts as a double-edged sword during septic shock. Consequently, the focus has shifted towards selective inducible NOS (iNOS) inhibitors. The contribution of NO to anaphylactic shock seems to be more straightforward, as NOS inhibition abrogates shock in conscious mice. Surprisingly, however, this shock-inducing NO is not produced by the inducible iNOS, but by the so-called constitutive enzyme endothelial NOS. This review summarizes the contribution of NO to septic and anaphylactic shock. Although NOS inhibition may be promising for the treatment of anaphylactic shock, the failure of a phase III trial indicates that other approaches are required for the successful treatment of septic shock. Amongst these, high hopes are set for selective iNOS inhibitors. But it might also be necessary to shift gears and focus on downstream cardiovascular targets of NO or on other vasodilating phenomena.

  8. Chemiluminescence of nitric oxide

    NASA Technical Reports Server (NTRS)

    Sharp, W. E.; Rusch, D. W.

    1981-01-01

    Measurements of the intensities of the delta and gamma bands of nitric oxide in the nighttime terrestrial thermosphere are presented and used to infer the rate coefficient for the transition from the C 2 Pi to the A 2 Sigma + states. The nightglow spectrum was observed between 1900 and 2300 A at a resolution of 15 A by a rocket-borne scanning 1/4-m spectrometer pointing north at an apogee of 150 km. Progressions of the delta, gamma and epsilon bands are identified on the spectra by the construction of synthetic spectra, and the contributions of resonance fluorescence to the total band intensities are calculated. Finally, the ratio of the sum of the gamma bands for v-prime = 0 to the sum of the delta bands for v-prime = 0 is used to derive a branching ratio of 0.21 + or - 0.04 to the A 2 Sigma + state, which yields a probability for the C-A transition of 5.6 + or - 1.5 x to the 6th/sec.

  9. Nitric oxide enhancement strategies

    PubMed Central

    Bryan, Nathan S

    2015-01-01

    It is becoming increasingly clear that many diseases are characterized or associated with perturbations in nitric oxide (NO) production/signaling. Therapeutics or strategies designed to restore normal NO homeostasis will likely have broad application and utility. This highly complex and multistep pathway for NO production and subsequent target activation provides many steps in the endogenous pathway that may be useful targets for drug development for cardiovascular disease, antimicrobial, cancer, wound healing, etc. This article will summarize known strategies that are currently available or in development for enhancing NO production or availability in the human body. Each strategy will be discussed including exogenous sources of NO, use of precursors to promote NO production and downstream pathways affected by NO production with advantages and disadvantages highlighted for each. Development of NO-based therapeutics is and will continue to be a major focus of biotech, academia as well as pharmaceutical companies. Application of safe and effective strategies will certainly transform health and disease. PMID:28031863

  10. Nitric Oxide Synthase Promotes Distension-Induced Tracheal Venular Leukocyte Adherence

    PubMed Central

    Moldobaeva, Aigul; Rentsendorj, Otgonchimeg; Jenkins, John; Wagner, Elizabeth M.

    2014-01-01

    The process of leukocyte recruitment to the airways in real time has not been extensively studied, yet airway inflammation persists as a major contributor to lung pathology. We showed previously in vivo, that neutrophils are recruited acutely to the large airways after periods of airway distension imposed by the application of positive end-expiratory pressure (PEEP). Given extensive literature implicating products of nitric oxide synthase (NOS) in lung injury after ventilatory over-distension, we questioned whether similar mechanisms exist in airway post-capillary venules. Yet, endothelial nitric oxide has been shown to be largely anti-inflammatory in other systemic venules. Using intravital microscopy to visualize post-capillary tracheal venules in anesthetized, ventilated mice, the number of adherent leukocytes was significantly decreased in eNOS-/- mice under baseline conditions (2±1 cell/60 min observation) vs wild type (WT) C57BL/6 mice (7±2 cells). After exposure to PEEP (8 cmH2O for 1 min; 5 times), adherent cells increased significantly (29±5 cells) in WT mice while eNOS-/- mice demonstrated a significantly decreased number of adherent cells (11±4 cells) after PEEP. A similar response was seen when thrombin was used as the pro-inflammatory stimulus. In addition, mouse tracheal venular endothelial cells studied in vitro after exposure to cyclic stretch (18% elongation) or thrombin both demonstrated increased p-selectin expression that was significantly attenuated by NG-nitro-L-arginine methyl ester, N-acetylcysteine amide (NACA) and excess BH4. In vivo treatment with the ROS inhibitor NACA or co-factor BH4 abolished completely the PEEP-induced leukocyte adherence. These results suggest that pro-inflammatory stimuli cause leukocyte recruitment to tracheal endothelium in part due to eNOS uncoupling. PMID:25181540

  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. Copyright © 2016 the American Physiological Society.

  12. Social support as a predictor exhaled nitric oxide in healthy individuals across time.

    PubMed

    Trueba, Ana F; Rosenfield, David; Smith, Noelle Bassi; Gorena, Tabitha L; Ritz, Thomas

    2014-09-01

    Psychosocial factors such as social support and depression have long been associated with health outcomes. Elevated depressive symptoms are usually associated with worse health outcomes, whereas social support has been related to improvements in health. Nitric oxide levels are an important marker of both cardiovascular health and immune function. Research suggests that exhaled nitric oxide is affected by stress, negative affect, and depression; however, the effect of social support has not been previously explored. Thus, we sought to examine the association of social support, negative affect, and depression with exhaled nitric oxide in a group of 35 healthy individuals (10 males and 25 females) with a mean age of 20.5years across five weekly assessments. Results showed that changes in social support within individuals were positively associated with levels of exhaled nitric oxide independent of other psychosocial factors. Further exploration of the health implications of this positive relationship between airway nitric oxide and social support is necessary. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Nasal and oral contribution to inhaled and exhaled nitric oxide: a study in tracheotomized patients.

    PubMed

    Törnberg, D C F; Marteus, H; Schedin, U; Alving, K; Lundberg, J O N; Weitzberg, E

    2002-05-01

    Nitric oxide (NO) is produced at different sites in the human airways and may have several physiological effects. Orally-produced NO seems to contribute to the levels found in exhaled air. Autoinhalation of nasal NO increases oxygenation and reduces pulmonary artery pressure in humans. The aim of this study was to measure the concentration and output of NO during nasal, oral and tracheal controlled exhalation and inhalation. Ten tracheotomized patients and seven healthy subjects were studied. The mean+/-SEM fraction of exhaled NO from the nose, mouth and trachea was 56+/-8, 14+/-4 and 6+/-1 parts per billion (ppb), respectively. During single-breath nasal, oral and tracheal inhalation the fraction of inhaled NO was 64+/-14, 11+/-3 and 4+/-1, respectively. There was a marked flow dependency on nasal NO output in the healthy subjects, which was four-fold greater at the higher flow rates, during inhalation when compared to exhalation. There is a substantial contribution of nasal and oral nitric oxide during both inhalation and exhalation. Nasal nitric oxide output is markedly higher during inhalation, reaching levels similar to those that are found to have clinical effects in the trachea. These findings have implications for the measurement of nitric oxide in exhaled air and the physiological effects of autoinhaled endogenous nitric oxide.

  14. The human airway epithelial basal cell transcriptome.

    PubMed

    Hackett, Neil R; Shaykhiev, Renat; Walters, Matthew S; Wang, Rui; Zwick, Rachel K; Ferris, Barbara; Witover, Bradley; Salit, Jacqueline; Crystal, Ronald G

    2011-05-04

    The human airway epithelium consists of 4 major cell types: ciliated, secretory, columnar and basal cells. During natural turnover and in response to injury, the airway basal cells function as stem/progenitor cells for the other airway cell types. The objective of this study is to better understand human airway epithelial basal cell biology by defining the gene expression signature of this cell population. Bronchial brushing was used to obtain airway epithelium from healthy nonsmokers. Microarrays were used to assess the transcriptome of basal cells purified from the airway epithelium in comparison to the transcriptome of the differentiated airway epithelium. This analysis identified the "human airway basal cell signature" as 1,161 unique genes with >5-fold higher expression level in basal cells compared to differentiated epithelium. The basal cell signature was suppressed when the basal cells differentiated into a ciliated airway epithelium in vitro. The basal cell signature displayed overlap with genes expressed in basal-like cells from other human tissues and with that of murine airway basal cells. Consistent with self-modulation as well as signaling to other airway cell types, the human airway basal cell signature was characterized by genes encoding extracellular matrix components, growth factors and growth factor receptors, including genes related to the EGF and VEGF pathways. Interestingly, while the basal cell signature overlaps that of basal-like cells of other organs, the human airway basal cell signature has features not previously associated with this cell type, including a unique pattern of genes encoding extracellular matrix components, G protein-coupled receptors, neuroactive ligands and receptors, and ion channels. The human airway epithelial basal cell signature identified in the present study provides novel insights into the molecular phenotype and biology of the stem/progenitor cells of the human airway epithelium.

  15. The Human Airway Epithelial Basal Cell Transcriptome

    PubMed Central

    Wang, Rui; Zwick, Rachel K.; Ferris, Barbara; Witover, Bradley; Salit, Jacqueline; Crystal, Ronald G.

    2011-01-01

    Background The human airway epithelium consists of 4 major cell types: ciliated, secretory, columnar and basal cells. During natural turnover and in response to injury, the airway basal cells function as stem/progenitor cells for the other airway cell types. The objective of this study is to better understand human airway epithelial basal cell biology by defining the gene expression signature of this cell population. Methodology/Principal Findings Bronchial brushing was used to obtain airway epithelium from healthy nonsmokers. Microarrays were used to assess the transcriptome of basal cells purified from the airway epithelium in comparison to the transcriptome of the differentiated airway epithelium. This analysis identified the “human airway basal cell signature” as 1,161 unique genes with >5-fold higher expression level in basal cells compared to differentiated epithelium. The basal cell signature was suppressed when the basal cells differentiated into a ciliated airway epithelium in vitro. The basal cell signature displayed overlap with genes expressed in basal-like cells from other human tissues and with that of murine airway basal cells. Consistent with self-modulation as well as signaling to other airway cell types, the human airway basal cell signature was characterized by genes encoding extracellular matrix components, growth factors and growth factor receptors, including genes related to the EGF and VEGF pathways. Interestingly, while the basal cell signature overlaps that of basal-like cells of other organs, the human airway basal cell signature has features not previously associated with this cell type, including a unique pattern of genes encoding extracellular matrix components, G protein-coupled receptors, neuroactive ligands and receptors, and ion channels. Conclusion/Significance The human airway epithelial basal cell signature identified in the present study provides novel insights into the molecular phenotype and biology of the stem

  16. Distal appendicitis: CT appearance and diagnosis.

    PubMed

    Rao, P M; Rhea, J T; Novelline, R A

    1997-09-01

    To determine the appearance of appendicitis in the distal part of the organ (distal appendicitis) on computed tomographic (CT) scans and to evaluate the accuracy of diagnosis based on CT findings. CT scans and medical records in 180 consecutive patients with proved appendicitis were reviewed. Fourteen had distal appendicitis with at least a 3-cm length of normal proximal appendix. Appendiceal CT scans and initial reports were reviewed retrospectively. The proximal appendix was collapsed (n = 6) or was filled with contrast material (n = 6) or air (n = 2). Inflamed distal appendices averaged 13.2 mm in diameter and were associated with periappendiceal fat stranding (n = 14), adenopathy (n = 6), appendolith(s) (n = 4), or fluid (n = 2). Transition points consisted of a progressively narrowed appendiceal lumen and thickened wall (n = 5) or appendiceal diameter enlargement (n = 9). No cecal apical changes were seen. Scans in all 14 patients were prospectively interpreted as indicative of appendicitis, including 12 (86%) interpreted as indicative of distal appendicitis. CT findings are useful for the accurate diagnosis of distal appendicitis. Visualization of the proximal appendix alone is insufficient to exclude distal appendicitis.

  17. Updates of operative techniques for upper airway stimulation.

    PubMed

    Heiser, Clemens; Thaler, Erica; Boon, Maurits; Soose, Ryan J; Woodson, B Tucker

    2016-09-01

    Selective upper airway stimulation has been established as an additional treatment for obstructive sleep apnea (OSA). Essential for the treatment is the precise placement of the cuff electrode for select branches of the hypoglossal nerve, which innervate the protrusors and stiffeners of the tongue. A direct approach to the distal hypoglossal nerve has been established to achieve this goal. For surgeons, detailed knowledge of this anatomy is vital. Another decisive step is the placement of the sensing lead between the intercostal muscles. Also, the complexity of follow-up care postoperatively should be kept in mind. The aim of this article is to provide the latest knowledge on the neuroanatomy of the hypoglossal nerve and to give surgeons a step-by-step guide on the current operative technique. Laryngoscope, 126:S12-S16, 2016. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

  18. Airway nerves: in vitro electrophysiology.

    PubMed

    Fox, Alyson

    2002-06-01

    Recording the activity of single airway sensory fibres or neuronal cell bodies in vitro has allowed detailed characterisation of fibre types and membrane properties. Fibre types can be identified by their conduction velocities and further studied by the application of drugs to their receptive field. C-fibres are sensitive to mechanical stimuli and a range of irritant chemicals (bradykinin, capsaicin, low pH, platelet-activating factor), whereas Adelta-fibres are relatively insensitive to chemical stimuli and appear to correlate to the rapidly adapting receptors identified in airways in vivo. Their site of origin also differs: upper airway C-fibres arise predominantly from the jugular ganglion and Adelta-fibres from the jugular and nodose ganglia. Intracellular recording from cell bodies in the ganglia has revealed a calcium-dependent potassium current common to many putative C-fibre cell bodies. This slow after hyperpolarisation current may be inhibited by stimuli that excite and sensitise C-fibres - this could be an important mechanism underlying the sensitisation of C-fibres in airway irritability.

  19. 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.

  20. Inflammatory bowel disease and airway diseases.

    PubMed

    Vutcovici, Maria; Brassard, Paul; Bitton, Alain

    2016-09-14

    Airway diseases are the most commonly described lung manifestations of inflammatory bowel disease (IBD). However, the similarities in disease pathogenesis and the sharing of important environmental risk factors and genetic susceptibility suggest that there is a complex interplay between IBD and airway diseases. Recent evidence of IBD occurrence among patients with airway diseases and the higher than estimated prevalence of subclinical airway injuries among IBD patients support the hypothesis of a two-way association. Future research efforts should be directed toward further exploration of this association, as airway diseases are highly prevalent conditions with a substantial public health impact.

  1. The Lung Microbiome and Airway Disease.

    PubMed

    Lynch, Susan V

    2016-12-01

    A growing body of literature has demonstrated relationships between the composition of the airway microbiota (mixed-species communities of microbes that exist in the respiratory tract) and critical features of immune response and pulmonary function. These studies provide evidence that airway inflammatory status and capacity for repair are coassociated with specific taxonomic features of the airway microbiome. Although directionality has yet to be established, the fact that microbes are known drivers of inflammation and tissue damage suggests that in the context of chronic inflammatory airway disease, the composition and, more importantly, the function, of the pulmonary microbiome represent critical factors in defining airway disease outcomes.

  2. Genetics Home Reference: distal hereditary motor neuropathy, type II

    MedlinePlus

    ... Conditions distal hereditary motor neuropathy, type II distal hereditary motor neuropathy, type II Printable PDF Open All ... to view the expand/collapse boxes. Description Distal hereditary motor neuropathy, type II is a progressive disorder ...

  3. Elbow dislocation with ipsilateral distal radius fracture

    PubMed Central

    Meena, Sanjay; Trikha, Vivek; Kumar, Rakesh; Saini, Pramod; Sambharia, Abhishek Kumar

    2013-01-01

    Elbow dislocation associated with ipsilateral distal radius fracture is a rare pattern of injury, although it is common for elbow dislocation and forearm fractures to occur separately. We report a rare case of a 20-year-old male who had a posterior elbow dislocation and ipsilateral distal radius fracture. Elbow dislocation was first reduced in extension and distal radius fracture was then reduced in flexion. Both the injuries were conservatively managed. At 6 months follow-up, the patient had no pain in his elbow and minimal pain in his wrist on heavy lifting and had resumed his work as a laborer. PMID:24082758

  4. Elbow dislocation with ipsilateral distal radius fracture.

    PubMed

    Meena, Sanjay; Trikha, Vivek; Kumar, Rakesh; Saini, Pramod; Sambharia, Abhishek Kumar

    2013-07-01

    Elbow dislocation associated with ipsilateral distal radius fracture is a rare pattern of injury, although it is common for elbow dislocation and forearm fractures to occur separately. We report a rare case of a 20-year-old male who had a posterior elbow dislocation and ipsilateral distal radius fracture. Elbow dislocation was first reduced in extension and distal radius fracture was then reduced in flexion. Both the injuries were conservatively managed. At 6 months follow-up, the patient had no pain in his elbow and minimal pain in his wrist on heavy lifting and had resumed his work as a laborer.

  5. Unilateral Molar Distalization: A Nonextraction Therapy

    PubMed Central

    Prasad, M. Bhanu; Sreevalli, S.

    2012-01-01

    In the recent years, nonextraction treatment approaches and noncompliance therapies have become more popular in the correction of space discrepancies. One of the conventional approaches for space gaining in the arches without patient compliance is done by using certain extra oral appliances or intraoral appliance. The greatest advantage of certain appliances like fixed functional and molar distalization appliances is that they minimize the dependence on patient cooperation. Molar distalization appliances like pendulum appliance which distalizes the molar rapidly without the need of head gear can be used in patients as a unilateral space gaining procedure due to buccal segment crowding. PMID:23320203

  6. Semiconstrained Distal Radioulnar Joint Prosthesis

    PubMed Central

    Savvidou, Christiana; Murphy, Erin; Mailhot, Emilie; Jacob, Shushan; Scheker, Luis R.

    2013-01-01

    Distal radioulnar joint (DRUJ) problems can occur as a result of joint instability, abutment, or incongruity. The DRUJ is a weight-bearing joint; the ulnar head is frequently excised either totally or partially, and in some cases it is fused, because of degenerative, rheumatoid, or posttraumatic arthritis. Articles about these procedures report the ability to pronate and supinate, but they rarely discuss grip strength, and even less do they address lifting capacity. We report the long term results of the first 35 patients who underwent total DRUJ arthroplasty with the Aptis DRUJ prosthesis after 5 years follow-up. Surgical indications were all causes of dysfunctional DRUJ (degenerative, posttraumatic, autoimmune, congenital). We recorded data for patient demographics, range of motion (ROM), strength, and lifting capacity of the operated and of the nonoperated extremity. Pain and functional assessments were also recorded. The Aptis DRUJ prosthesis, a bipolar self-stabilizing DRUJ endoprosthesis that restores forearm function, consists of a semiconstained and modular implant designed to replace the function of the ulnar head, the sigmoid notch of the radius, and the triangular fibrocartilage ligaments. The surgical technique is presented in detail. The majority of the patients regained adequate ROM and improved their strength and lifting capacity to the operated side. Pain and activities of daily living were improved. Twelve patients experienced complications, most commonly being extensor carpi ulnaris (ECU) tendinitis, ectopic bone formation, bone resorption with stem loosening, low-grade infection, and need for ball replacement. The Aptis total DRUJ replacement prosthesis is an alternative to salvage procedures that enables a full range of motion as well as the ability to grip and lift weights encountered in daily living activities. PMID:24436788

  7. Airway management in anaplastic thyroid carcinoma.

    PubMed

    Shaha, Ashok R

    2008-07-01

    In patients who present with advanced anaplastic thyroid cancer, airway management is difficult because of bilateral vocal cord paralysis or tracheal invasion by the tumor. Airway management can be extremely complex in these patients. This is the author's 25 year experience with 30 patients who presented with anaplastic thyroid cancer and acute airway problems. The patients' airway issues developed soon after presentation or a few months after treatment. Ten patients presented with initial symptoms of acute airway distress. All of these patients were treated with tracheostomy or cricothyrotomy. The 10 patients who presented with initial symptoms of acute airway distress died within 4 months. Eight of the remaining 20 patients developed bilateral vocal cord paralysis. Airway management for these patients depended on the extent of distant disease and the family's understanding of the advanced nature of the disease and the palliative efforts. The remaining patients had a palliative and supportive approach. Airway management was the most critical issue in patients who presented with anaplastic thyroid cancer and initial airway distress. Cricothyrotomy was helpful in avoiding acute airway catastrophe. It is important to distinguish between poorly differentiated and anaplastic thyroid cancer and lymphoma for appropriate airway management.

  8. Airway malacia in children with achondroplasia.

    PubMed

    Dessoffy, Kimberly E; Modaff, Peggy; Pauli, Richard M

    2014-02-01

    This study was undertaken to assess the frequency of airway malacia in infants and young children with achondroplasia, a population well known to be at risk for a variety of respiratory problems. We also wished to evaluate what, if any, contribution airway malacia makes to the complex respiratory issues that may be present in those with achondroplasia. Retrospective chart review of all infants and young children with achondroplasia who were assessed through the Midwest Regional Bone Dysplasia Clinics from 1985 through 2012 (n = 236) was completed. Records of comprehensive clinical examinations, polysomnographic assessments, and airway visualization were reviewed and abstracted using a data collection form. Analyses were completed comparing the group with and those without evidence for airway malacia. Thirteen of 236 patients (5.5%) were found to have airway malacia. Most of those affected had lower airway involvement (9/13). The presence of airway malacia was correlated with an increased occurrence of obstructive sleep apnea as well as need for oxygen supplementation, airway surgeries and tracheostomy placement. Although estimates of the frequency of airway malacia in the general population are limited, its frequency in children with achondroplasia appears to be much higher than any published general population estimate. The presence of airway malacia appears to confound other breathing abnormalities in this population and results in the need for more invasive airway treatments.

  9. Native Small Airways Secrete Bicarbonate

    PubMed Central

    Quinton, Paul M.

    2014-01-01

    Since the discovery of Cl− impermeability in cystic fibrosis (CF) and the cloning of the responsible channel, CF pathology has been widely attributed to a defect in epithelial Cl− transport. However, loss of bicarbonate (HCO3−) transport also plays a major, possibly more critical role in CF pathogenesis. Even though HCO3− transport is severely affected in the native pancreas, liver, and intestines in CF, we know very little about HCO3− secretion in small airways, the principle site of morbidity in CF. We used a novel, mini-Ussing chamber system to investigate the properties of HCO3− transport in native porcine small airways (∼ 1 mm φ). We assayed HCO3− transport across small airway epithelia as reflected by the transepithelial voltage, conductance, and equivalent short-circuit current with bilateral 25-mM HCO3− plus 125-mM NaGlu Ringer’s solution in the presence of luminal amiloride (10 μM). Under these conditions, because no major transportable anions other than HCO3− were present, we took the equivalent short-circuit current to be a direct measure of active HCO3− secretion. Applying selective agonists and inhibitors, we show constitutive HCO3− secretion in small airways, which can be stimulated significantly by β-adrenergic– (cAMP) and purinergic (Ca2+) -mediated agonists, independently. These results indicate that two separate components for HCO3− secretion, likely via CFTR- and calcium-activated chloride channel–dependent processes, are physiologically regulated for likely roles in mucus clearance and antimicrobial innate defenses of small airways. PMID:24224935

  10. Exposure to hog barn dust alters airway epithelial ciliary beating.

    PubMed

    Wyatt, T A; Sisson, J H; Von Essen, S G; Poole, J A; Romberger, D J

    2008-06-01

    Swine confinement workers are at increased risk of airway diseases, including mucus membrane irritation syndrome, chronic rhinosinusitis and chronic bronchitis. Dust extracts from swine confinement facilities stimulate the production of pro-inflammatory cytokines in bronchial epithelial cells, including interleukin (IL)-8. As IL-8 is capable of blocking beta-agonist-stimulated increases in cilia beating, which impacts on mucociliary clearance, it was hypothesised that hog barn-dust exposure might alter cilia responses to stimulation. To test this hypothesis, ciliated bovine bronchial epithelial cell cultures were exposed to hog barn-dust extract (HDE) and ciliary beat frequency (CBF) was assayed. An elevation in baseline CBF was observed. This effect appeared to be independent of endotoxin but dependent upon nitric oxide. HDE also stimulated nitric oxide production in bronchial epithelial cells; however, stimulation of cilia beating by a beta-agonist did not occur in cells pre-exposed to HDE. These data demonstrate that hog barn dust can alter normal stimulation of cilia, suggesting a mechanism for the abrogation of stimulated increases in mucociliary clearance in response to inhaled dust exposure.

  11. 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.

  12. Exhaled pH, exhaled nitric oxide, and induced sputum cellularity in obese patients with obstructive sleep apnea syndrome.

    PubMed

    Carpagnano, Giovanna E; Spanevello, Antonio; Sabato, Roberto; Depalo, Annarita; Turchiarelli, Viviana; Foschino Barbaro, Maria Pia

    2008-01-01

    Airway inflammation plays an important role in obstructive sleep apnea syndrome as well as in obesity. Increasingly, researchers are studying airway inflammation noninvasively and are studying the new markers of airways inflammation. The aim of this study was to measure pH in the exhaled breath condensate (EBC), the exhaled nitric oxide (NO), and the inflammatory cell profile in the induced sputum of obese patients with and without obstructive sleep apnea syndrome (OSAS). The pH in EBC, the exhaled NO, and the induced sputum cells were measured in 30 obese patients with OSAS (OOs), in 20 obese patients without OSAS (ONOs), and in 10 healthy patients (HPs). Levels of pH in EBC were lower in OOs and in ONOs than in HPs. Furthermore, the concentrations of exhaled NO and the percentages of neutrophils in the induced sputum were greater in OOs and in ONOs than in HPs. No significant differences were found between OO and ONO for other measurements of airway inflammation. This study shows the presence of airway's inflammation in obese patients with and without OSAS and indicates that the "exhaled acidopnea" as well as exhaled NO and sputum neutrophils are good tools to measure airway inflammation in these subjects.

  13. Decreased levels of nitrosothiols in the lower airways of patients with cystic fibrosis and normal pulmonary function.

    PubMed

    Grasemann, H; Gaston, B; Fang, K; Paul, K; Ratjen, F

    1999-12-01

    Airway S-nitrosothiols (SNOs) are naturally occurring bronchodilators. SNOs, nitrate, and nitrite were measured in bronchoalveolar lavage fluid of 23 patients with cystic fibrosis (CF) and mild pulmonary disease (aged 6-16 years) and 13 healthy children (aged 8-15 years). Concentrations of SNOs were decreased in the lower airways of patients with CF and mild pulmonary disease (median, range: 0, 0-320 nmol/L vs 80, 0-970 nmol/L) despite normal levels of the inert nitric oxide metabolites nitrate and nitrite (mean +/- SEM: 3.7 +/- 0.5 micromol/L vs 4.8 +/- 0.9 micromol/L). S-nitrosolation- mediated bioreactivities may be impaired by depletion of the CF airway SNO reservoir.

  14. Increased levels of exhaled nitric oxide during nasal and oral breathing in subjects with seasonal rhinitis.

    PubMed

    Martin, U; Bryden, K; Devoy, M; Howarth, P

    1996-03-01

    Allergic rhinitis is associated with nasal mucosal inflammation. Exhaled nitric oxide may be a useful marker of inflammation and has recently been shown to be increased in patients with asthma. The purpose of this study was to determine whether exhaled levels of nitric oxide are increased with nasal breathing in patients with seasonal allergic rhinitis compared with nonatopic individuals and whether there is an increase with oral breathing consistent with lower respiratory inflammation in the absence of clinical asthma. Nitric oxide levels in exhaled air were measured by chemiluminescence in 18 nonatopic volunteers and 32 patients with seasonal rhinitis. Measurements were made with both nasal and oral exhalation and orally after 10 seconds and 60 seconds of breath-holding. The detection limit was 1 part per billion (ppb). In control subjects nasal levels of nitric oxide in exhaled air (mean +/- SD, 24.7 +/- 9.2 ppb) were higher than those after oral exhalation (11.1 +/- 2.5 ppb, p less than 0.0001). Breath-holding significantly increased levels of nitric oxide in exhaled air in a time-dependent manner. Levels of exhaled nitric oxide were significantly higher for all measurements in patients with seasonal rhinitis, with levels without breath-holding of 35.4 +/- 11.3 ppb (p less than 0.001) in nasally exhaled air and 16.3 +/- 5.9 ppb (p less than 0.001) in orally exhaled air. Nasal levels were significantly higher than oral levels in subjects with rhinitis (p less than 0.0001). The results indicate that exhaled nitric oxide may be a useful marker for nasal inflammation in patients with seasonal rhinitis and suggest that generalized airway inflammation may be present, even without clinical asthma, in such patients.

  15. Degrees of reality: airway anatomy of high-fidelity human patient simulators and airway trainers.

    PubMed

    Schebesta, Karl; Hüpfl, Michael; Rössler, Bernhard; Ringl, Helmut; Müller, Michael P; Kimberger, Oliver

    2012-06-01

    Human patient simulators and airway training manikins are widely used to train airway management skills to medical professionals. Furthermore, these patient simulators are employed as standardized "patients" to evaluate airway devices. However, little is known about how realistic these patient simulators and airway-training manikins really are. This trial aimed to evaluate the upper airway anatomy of four high-fidelity patient simulators and two airway trainers in comparison with actual patients by means of radiographic measurements. The volume of the pharyngeal airspace was the primary outcome parameter. Computed tomography scans of 20 adult trauma patients without head or neck injuries were compared with computed tomography scans of four high-fidelity patient simulators and two airway trainers. By using 14 predefined distances, two cross-sectional areas and three volume parameters of the upper airway, the manikins' similarity to a human patient was assessed. The pharyngeal airspace of all manikins differed significantly from the patients' pharyngeal airspace. The HPS Human Patient Simulator (METI®, Sarasota, FL) was the most realistic high-fidelity patient simulator (6/19 [32%] of all parameters were within the 95% CI of human airway measurements). The airway anatomy of four high-fidelity patient simulators and two airway trainers does not reflect the upper airway anatomy of actual patients. This finding may impact airway training and confound comparative airway device studies.

  16. Airway remodeling in asthma: what really matters.

    PubMed

    Fehrenbach, Heinz; Wagner, Christina; Wegmann, Michael

    2017-03-01

    Airway remodeling is generally quite broadly defined as any change in composition, distribution, thickness, mass or volume and/or number of structural components observed in the airway wall of patients relative to healthy individuals. However, two types of airway remodeling should be distinguished more clearly: (1) physiological airway remodeling, which encompasses structural changes that occur regularly during normal lung development and growth leading to a normal mature airway wall or as an acute and transient response to injury and/or inflammation, which ultimately results in restoration of a normal airway structures; and (2) pathological airway remodeling, which comprises those structural alterations that occur as a result of either disturbed lung development or as a response to chronic injury and/or inflammation leading to persistently altered airway wall structures and function. This review will address a few major aspects: (1) what are reliable quantitative approaches to assess airway remodeling? (2) Are there any indications supporting the notion that airway remodeling can occur as a primary event, i.e., before any inflammatory process was initiated? (3) What is known about airway remodeling being a secondary event to inflammation? And (4), what can we learn from the different animal models ranging from invertebrate to primate models in the study of airway remodeling? Future studies are required addressing particularly pheno-/endotype-specific aspects of airway remodeling using both endotype-specific animal models and "endotyped" human asthmatics. Hopefully, novel in vivo imaging techniques will be further advanced to allow monitoring development, growth and inflammation of the airways already at a very early stage in life.

  17. Does Moderate Intensity Exercise Attenuate the Postprandial Lipemic and Airway Inflammatory Response to a High-Fat Meal?

    PubMed Central

    Kurti, Stephanie P.; Rosenkranz, Sara K.; Levitt, Morton; Cull, Brooke J.; Teeman, Colby S.; Emerson, Sam R.; Harms, Craig A.

    2015-01-01

    We investigated whether an acute bout of moderate intensity exercise in the postprandial period attenuates the triglyceride and airway inflammatory response to a high-fat meal (HFM) compared to remaining inactive in the postprandial period. Seventeen (11 M/6 F) physically active (≥150 min/week of moderate-vigorous physical activity (MVPA)) subjects were randomly assigned to an exercise (EX; 60% VO2peak) or sedentary (CON) condition after a HFM (10 kcal/kg, 63% fat). Blood analytes and airway inflammation via exhaled nitric oxide (eNO) were measured at baseline, and 2 and 4 hours after HFM. Airway inflammation was assessed with induced sputum and cell differentials at baseline and 4 hours after HFM. Triglycerides doubled in the postprandial period (~113 ± 18%, P < 0.05), but the increase did not differ between EX and CON. Percentage of neutrophils was increased 4 hours after HFM (~17%), but the increase did not differ between EX and CON. Exhaled nitric oxide changed nonlinearly from baseline to 2 and 4 hours after HFM (P < 0.05,  η2 = 0.36). Our findings suggest that, in active individuals, an acute bout of moderate intensity exercise does not attenuate the triglyceride or airway inflammatory response to a high-fat meal. PMID:26000301

  18. Air contamination with nitric oxide: effect on exhaled nitric oxide response.

    PubMed

    Therminarias, A; Flore, P; Favre-Juvin, A; Oddou, M F; Delaire, M; Grimbert, F

    1998-03-01

    This study examines the response of exhaled nitric oxide (NO) concentration (ECNO) and quantity of exhaled NO over time (EVNO) in 10 healthy subjects breathing into five polyethylene bags, one in which synthetic air was free of NO and four in which NO was diluted to concentrations of 20 +/- 0.6, 49 +/- 0.8, 98 +/- 2, and 148 +/- 2 ppb, respectively. Each subject was connected to each bag for 10 min at random. Minute ventilation and ECNO were measured continuously, and EVNO was calculated continuously. ECNO and EVNO values were significantly higher for an inhaled NO concentration of 20 ppb than for NO-free air. Above 20 ppb, ECNO and EVNO increased linearly with inhaled NO concentration. It is reasonable to assume that a share of the quantity of inspired NO over time (InspVNO) because of air contamination by pollution is rejected by the ventilatory pathway. Insofar as InspVNO does not affect endogenous production or the metabolic fate of NO in the airway, this share may be estimated as being approximately one third of InspVNO, the remainder being taken by the endogenous pathway. Thus, air contamination by the NO resulting from pollution greatly increases the NO response in exhaled air.

  19. Epithelial Notch signaling regulates lung alveolar morphogenesis and airway epithelial integrity

    PubMed Central

    Tsao, Po-Nien; Matsuoka, Chisa; Wei, Shu-Chen; Sato, Atsuyasu; Sato, Susumu; Hasegawa, Koichi; Chen, Hung-kuan; Ling, Thai-Yen; Mori, Munemasa; Cardoso, Wellington V.; Morimoto, Mitsuru

    2016-01-01

    Abnormal enlargement of the alveolar spaces is a hallmark of conditions such as chronic obstructive pulmonary disease and bronchopulmonary dysplasia. Notch signaling is crucial for differentiation and regeneration and repair of the airway epithelium. However, how Notch influences the alveolar compartment and integrates this process with airway development remains little understood. Here we report a prominent role of Notch signaling in the epithelial–mesenchymal interactions that lead to alveolar formation in the developing lung. We found that alveolar type II cells are major sites of Notch2 activation and show by Notch2-specific epithelial deletion (Notch2cNull) a unique contribution of this receptor to alveologenesis. Epithelial Notch2 was required for type II cell induction of the PDGF-A ligand and subsequent paracrine activation of PDGF receptor-α signaling in alveolar myofibroblast progenitors. Moreover, Notch2 was crucial in maintaining the integrity of the epithelial and smooth muscle layers of the distal conducting airways. Our data suggest that epithelial Notch signaling regulates multiple aspects of postnatal development in the distal lung and may represent a potential target for intervention in pulmonary diseases. PMID:27364009

  20. Specific coronary drug-eluting stents interfere with distal microvascular function after single stent implantation in pigs.

    PubMed

    van den Heuvel, Mieke; Sorop, Oana; Batenburg, Wendy W; Bakker, Charlotte L; de Vries, René; Koopmans, Sietse Jan; van Beusekom, Heleen M M; Duncker, Dirk J; Danser, A H Jan; van der Giessen, Willem J

    2010-07-01

    The aim of this study was to compare the effects of single drug-eluting stents (DES) on porcine coronary function distal to the stent in vivo and in vitro. The mechanism of endothelial dysfunction occurring in human coronary conduit arteries up to 9 months after DES implantation is unknown. A sirolimus-eluting stent (SES), paclitaxel-eluting stent (PES), and a bare-metal stent (BMS) were implanted in the 3 coronary arteries of 11 pigs. After 5 weeks, in vivo responses in distal coronary flow to different doses of bradykinin (BK) and nitrates were measured. In vitro, vasodilation to BK and nitrates, as well as vasoconstriction to endothelin (ET)-1 were assessed in both distal coronary conduit and small arteries. In addition, contributions of nitric oxide (NO) and endothelium-derived hyperpolarizing factors (EDHFs) and cyclic guanosine monophosphate (cGMP) responses to BK-stimulation were determined in vitro. Both DES did not alter in vivo distal vasomotion. In vitro distal conduit and small arterial responses to BK were also unaltered; DES did not alter the BK-induced increase in cGMP. However, after NO synthase blockade, PES showed a reduced BK-response in distal small arteries as compared with BMS and SES (p < 0.05). The ET-1-induced vasoconstriction and vascular smooth muscle cell function were unaltered. In this study of single stenting in healthy porcine coronaries for 5 weeks, SES did not affect distal coronary vascular function, whereas PES altered distal endothelial function of small arteries under conditions of reduced NO bioavailability. Therefore, specifically the EDHF component of microvascular function seems affected by PES. Copyright 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  1. Villous adenoma of the distal appendix.

    PubMed

    Taylor, J V; Thomas, M G; Kelly, S; Sutton, R

    1997-04-01

    Villous adenoma confined to the distal appendix has not been previously reported in conjunction with acute apendicitis. The presence of an adenoma indicates a need for further investigation due to an association with neoplasia elsewhere.

  2. Distal radius fractures in the athlete.

    PubMed

    Beleckas, Casey; Calfee, Ryan

    2017-03-01

    Distal radius fractures are one of the most common upper extremity fractures. Athletes with distal radius fractures are treated according to the same principles as non-athletes but present several unique considerations. At all levels of sport, injured athletes desire to return to play as rapidly as possible. Earlier operative fixation may allow an athlete to return to play more quickly. Volar locking plates are most commonly used for operative treatment of distal radius fractures due to their stability and low incidence of complications. Although the majority of distal radius fractures in athletes are treated non-operatively, operative intervention is offered when required to restore and maintain acceptable skeletal alignment. Return to sport is individualized guided by fracture stability, athlete age, and wrist-specific demands for competition.

  3. Genetics Home Reference: Laing distal myopathy

    MedlinePlus

    ... Laing distal myopathy is a condition that affects skeletal muscles, which are muscles that the body uses for ... in heart (cardiac) muscle and in type I skeletal muscle fibers. Type I fibers, which are also known ...

  4. Functional imaging using computer methods to compare the effect of salbutamol and ipratropium bromide in patient-specific airway models of COPD

    PubMed Central

    De Backer, LA; Vos, WG; Salgado, R; De Backer, JW; Devolder, A; Verhulst, SL; Claes, R; Germonpré, PR; De Backer, WA

    2011-01-01

    Background Salbutamol and ipratropium bromide improve lung function in patients with chronic obstructive pulmonary disease (COPD). However, their bronchodilating effect has not yet been compared in the central and distal airways. Functional imaging using computational fluid dynamics offers the possibility of making such a comparison. The objective of this study was to assess the effects of salbutamol and ipratropium bromide on the geometry and computational fluid dynamics-based resistance of the central and distal airways. Methods Five patients with Global Initiative for Chronic Obstructive Lung Disease Stage III COPD were randomized to a single dose of salbutamol or ipratropium bromide in a crossover manner with a 1-week interval between treatments. Patients underwent lung function testing and a multislice computed tomography scan of the thorax that was used for functional imaging. Two hours after dosing, the patients again underwent lung function tests and repeat computed tomography. Results Lung function parameters, including forced expiratory volume in 1 second, vital capacity, overall airway resistance, and specific airway resistance, changed significantly after administration of each product. On functional imaging, the bronchodilating effect was greater in the distal airways, with a corresponding drop in airway resistance, compared with the central airways. Salbutamol and ipratropium bromide were equally effective at first glance when looking at lung function tests, but when viewed in more detail with functional imaging, hyporesponsiveness could be shown for salbutamol in one patient. Salbutamol was more effective in the other patients. Conclusion This pilot study gives an innovative insight into the modes of action of salbutamol and ipratropium bromide in patients with COPD, using the new techniques of functional imaging and computational fluid dynamics. PMID:22162649

  5. 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

  6. Exhaled nitric oxide in childhood asthma: a review.

    PubMed

    Pijnenburg, M W H; De Jongste, J C

    2008-02-01

    As an 'inflammometer', the fraction of nitric oxide in exhaled air (Fe(NO)) is increasingly used in the management of paediatric asthma. Fe(NO) provides us with valuable, additional information regarding the nature of underlying airway inflammation, and complements lung function testing and measurement of airway hyper-reactivity. This review focuses on clinical applications of Fe(NO) in paediatric asthma. First, Fe(NO) provides us with a practical tool to aid in the diagnosis of asthma and distinguish patients who will benefit from inhaled corticosteroids from those who will not. Second, Fe(NO) is helpful in predicting exacerbations, and predicting successful steroid reduction or withdrawal. In atopic asthmatic children Fe(NO) is beneficial in adjusting steroid doses, discerning those patients who require additional therapy from those whose medication dose could feasibly be reduced. In pre-school children Fe(NO) may be of help in the differential diagnosis of respiratory symptoms, and may potentially allow for better targeting and monitoring of anti-inflammatory treatment.

  7. Nasal nitric oxide in sleep-disordered breathing in children.

    PubMed

    Gut, Guy; Tauman, Riva; Greenfeld, Michal; Armoni-Domany, Keren; Sivan, Yakov

    2016-03-01

    Inflammation plays a role in the pathogenesis and consequences of sleep-disordered breathing (SDB). The nasal mucosa and paranasal sinuses produce high levels of nitric oxide (NO). In asthma, exhaled NO is a marker of airway inflammation. There is only limited information whether nasal NO (nNO) accompanies also chronic upper airway obstruction, specifically, SDB. The objective of this study was to investigate nNO levels in children with SDB in comparison to healthy non-snoring children. Nasal NO was measured in children who underwent overnight polysomnographic studies due to habitual snoring and suspected SDB and in healthy non-snoring controls. One hundred and eleven children participated in the study: 28 with obstructive sleep apnea (OSA), 60 with primary snoring (PS), and 23 controls. Nasal NO levels were significantly higher in children with OSA and PS compared to controls (867.4 ± 371.5, 902.0 ± 330.9, 644.1 ± 166.5 ppb, respectively, p = 0.047). No difference was observed between children with OSA and PS. No correlations were found between nNO levels and any of the PSG variables, nor with age, BMI percentile or tonsils size. Compared to healthy controls, nNO is increased in children with SDB, but it is not correlated with disease severity. This is probably due to the local mechanical processes and snoring.

  8. Effects of an acute bout of moderate-intensity exercise on postprandial lipemia and airway inflammation.

    PubMed

    Johnson, Ariel M; Kurti, Stephanie P; Smith, Joshua R; Rosenkranz, Sara K; Harms, Craig A

    2016-03-01

    A high-fat meal (HFM) induces an increase in blood lipids (postprandial lipemia; PPL), systemic inflammation, and acute airway inflammation. While acute exercise has been shown to have anti-inflammatory and lipid-lowering effects, it is unknown whether exercise prior to an HFM will translate to reduced airway inflammation post-HFM. Our purpose was to determine the effects of an acute bout of exercise on airway inflammation post-HFM and to identify whether any protective effect of exercise on airway inflammation was associated with a reduction in PPL or systemic inflammation. In a randomized cross-over study, 12 healthy, 18- to 29-year-old men (age, 23.0 ± 3.2 years; height, 178.9 ± 5.5 cm; weight, 78.5 ± 11.7 kg) consumed an HFM (1 g fat/1 kg body weight) 12 h following exercise (EX; 60 min at 60% maximal oxygen uptake) or without exercise (CON). Fractional exhaled nitric oxide (FENO; measure of airway inflammation), triglycerides (TG), and inflammatory markers (high-sensitivity C-reactive protein, tumor-necrosis factor-alpha, and interleukin-6) were measured while fasted at 2 h and 4 h post-HFM. FENO increased over time (2 h: CON, p = 0.001; EX, p = 0.002, but not by condition (p = 0.991). TG significantly increased 2 and 4 h post-HFM (p < 0.001), but was not significant between conditions (p = 0.256). Inflammatory markers did not significantly increase by time or condition (p > 0.05). There were no relationships between FENO and TG or systemic inflammatory markers for any time point or condition (p > 0.05). In summary, an acute bout of moderate-intensity exercise performed 12 h prior to an HFM did not change postprandial airway inflammation or lipemia in healthy, 18- to 29-year-old men.

  9. Airway responsiveness to mannitol 24 h after allergen challenge in atopic asthmatics.

    PubMed

    Davis, B E; Amakye, D O; Cockcroft, D W

    2015-06-01

    Airway responsiveness to indirect stimuli correlates positively with airway inflammation. In atopic asthmatics, allergen inhalation is associated with an influx of inflammatory cells and increased responsiveness to the direct-acting stimuli methacholine at 3 and 24 h after exposure. We have shown mannitol responsiveness decreases 3 h after allergen inhalation. The current investigation assessed mannitol responsiveness 24 h after allergen challenge. Eleven mild atopic asthmatics completed allergen challenges on two separate occasions. In random order, methacholine or mannitol challenges were performed 24 h pre- and post-allergen challenge. Levels of fractional exhaled nitric oxide were also measured. Allergen challenge increased airway responsiveness to methacholine 24 h postchallenge; the geometric mean (95% CI) methacholine PC20 decreased from 5.9 mg/ml (1.8-19.4) to 2.2 mg/ml (0.81-5.89); P = 0.01. This coincided with a significant increase (P = 0.02) in FeNO levels. Conversely, allergen challenge decreased airway responsiveness to mannitol; geometric mean (95% CI) dose-response ratio was significantly higher after allergen exposure (57 mg/% FEV1 fall [27-121] to 147 mg/% FEV1 fall [57-379]; P = 0.03), and FeNO levels were not significantly increased (P = 0.054). Allergen-induced changes in airway responsiveness to direct and indirect stimuli are markedly different. The loss in responsiveness to mannitol is likely not explainable by a refractory state. The effect(s) of allergen exposure on airway responsiveness to indirect-acting stimuli require further investigation. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Dissociation constant of nitric acid

    NASA Astrophysics Data System (ADS)

    Levanov, A. V.; Isaikina, O. Ya.; Lunin, V. V.

    2017-07-01

    The composition of nitric acid solutions is investigated by means Raman spectroscopy (RS). The results are compared to critically selected data from other authors. The value of the thermodynamic dissociation constant in an aqueous nitric acid solution at 25°C ( K a = [ {{H^ + }} ]{[ {NO_3^ - } ]_{γ '}}_ ± ^2/[ {HN{O_3}} ]{γ '_{HN{O_3}}} = 35.5 ± 1.5M) is determined by analyzing an extensive set of reliable and consistent literature and original data. Expressions for the dependences of the activity coefficient of undissociated HNO3 molecules ({γ '_{HN{O_3}}} ) and the mean ionic coefficient ({γ '_ ± } = √ {{{γ '}_H} + {{γ '}_{NO_3^ - }}} ) on the stoichiometric concentration of nitric acid in the range of 0-18 M are found.

  11. A Novel Technique for Distal Shunt Revision: Retrospective Analysis of Guidewire-Assisted Distal Catheter Replacement.

    PubMed

    Sribnick, Eric A; Sklar, Frederick H; Wrubel, David M

    2015-09-01

    Ventriculoperitoneal shunt revision is a common procedure. Disconnection and fracture of the distal catheter remain a common cause of ventriculoperitoneal shunt malfunction. To describe a novel procedure for peritoneal replacement of the distal catheter by using a guidewire and a modified Seldinger technique (guidewire-assisted distal catheter replacement) and retrospectively evaluate the results of the surgical procedure. Between September 2005 and December 2013, 68 patients were treated by a single surgeon (DMW) with distal catheter replacement using our technique. In brief, the previously placed distal catheter was exposed at its entry site into the abdomen. A soft guidewire with hydrophilic coating was inserted down the distal catheter into the peritoneum. The distal catheter was then removed over the guidewire, leaving the guidewire in place. A peel-away sheath and dilator were then inserted over the guidewire, and the dilator and guidewire were removed. The new distal catheter was then passed from the valve to the abdomen and was then fed through the peel-away sheath into the peritoneum. Charts were retrospectively reviewed for preoperative presentation, operative technique, and postoperative outcome. Records were specifically examined for any early or late complications. The mean patient age at surgery was 13 years. No immediate acute complications were noted. Of the 68 total patients, 45 patients had more than 6 months of follow-up. Of the 68 patients, 7 patients required another distal revision after guidewire-assisted distal catheter replacement. Distal shunt malfunction due to a mechanical failure is a common reason for shunt revision. We describe a technique for guidewire-assisted distal catheter replacement.

  12. 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).

  13. Methodological aspects of exhaled nitric oxide measurements in infants.

    PubMed

    Gabriele, Carmelo; van der Wiel, Els C; Nieuwhof, Eveline M; Moll, Henriette A; Merkus, Peter J F M; de Jongste, Johan C

    2007-02-01

    Guidelines for the measurement of fractional exhaled nitric oxide (FE(NO)) recommend refraining from lung function tests (LFT) and certain foods and beverages before performing FE(NO) measurements, as they may lead to transiently altered FE(NO) levels. Little is known of such factors in infants. The aim of the present study was to evaluate whether forced expiratory maneuvers, sedation, nasal contamination, and breastfeeding affect FE(NO) values in infants. FE(NO) was measured off-line during tidal breathing by means of a facemask covering nose and mouth. FE(NO) measurements were performed in 45 sedated infants (mean age 12.1 months) who underwent LFT because of airway diseases and in 83 unsedated healthy infants (mean age 4.3 months). In infants with airway diseases, no difference was found in FE(NO) values before and 5 min after LFT (n = 19 infants, p = 0.7) and FE(NO) values before sedation did not differ from FE(NO) values during sedation (n = 10 infants, p = 0.2). Oral FE(NO) values were significantly lower than mixed (nasal + oral) FE(NO) (n = 42 infants, p < 0.001). FE(NO) values before and 5 min after breastfeeding were not different (n = 11 healthy infants, p = 0.57). The short-term reproducibility in healthy infants (n = 54) was satisfactory (intraclass correlation coefficient = 0.94). We conclude that, in infants with airway diseases, LFT prior to FE(NO) measurement did not influence FE(NO) values and FE(NO) values did not change after sedation. Oral FE(NO) values were significantly lower than mixed (oral + nasal) FE(NO), and breastfeeding did not influence FE(NO). Short-term reproducibility in awake healthy infants was good.

  14. Safranal of Crocus sativus L. inhibits inducible nitric oxide synthase and attenuates asthma in a mouse model of asthma.

    PubMed

    Bukhari, Syed Imran; Pattnaik, Bijay; Rayees, Sheikh; Kaul, Sanjana; Dhar, Manoj K

    2015-04-01

    The present study involves evaluation of antioxidant potential of Crocus sativus and its main constituents, safranal (SFN) and crocin (CRO), in bronchial epithelial cells, followed antiinflammatory potential of the active constituent safranal, in a murine model of asthma. To investigate the antioxidizing potential of Crocus sativus and its main constituents in bronchial epithelial cells, the stress was induced in these cells by a combination of different cytokines that resulted in an increase in nitric oxide production (NO), induced nitric oxide synthase (iNOS) levels, peroxynitrite ion generation, and cytochrome c release. Treatment with saffron and its constituents safranal and crocin resulted in a decrease of NO, iNOS levels, peroxynitrite ion generation, and prevented cytochrome c release. However, safranal significantly reduced oxidative stress in bronchial epithelial cells via iNOS reduction besides preventing apoptosis in these cells. In the murine model of asthma study, antiinflammatory role of safranal was characterized by increased airway hyper-responsiveness, airway cellular infiltration, and epithelial cell injury. Safranal pretreatment to these allergically inflamed mice lead to a significant decrease in airway hyper-responsiveness and airway cellular infiltration to the lungs. It also reduced iNOS production, bronchial epithelial cell apoptosis, and Th2 type cytokine production in the lungs.

  15. Expression of inducible nitric oxide in human lung epithelial cells.

    PubMed

    Robbins, R A; Barnes, P J; Springall, D R; Warren, J B; Kwon, O J; Buttery, L D; Wilson, A J; Geller, D A; Polak, J M

    1994-08-30

    Nitric oxide (NO) is increased in the exhaled air of subjects with several airway disorders. To determine if cytokines could stimulate epithelial cells accounting for the increased NO, the capacity of the proinflammatory cytokines (cytomix: tumor necrosis factor-alpha, interleukin-1 beta, and interferon-gamma) to increase inducible nitric oxide synthase (iNOS) was investigated in A549 and primary cultures of human bronchial epithelial cells. Cytomix induced a time-dependent increase in nitrite levels in culture supernatant fluids (p < 0.05). Increased numbers of cells stained for iNOS and increased iNOS mRNA was detected in the cytokine-stimulated cells compared to control (p < 0.05). Dexamethasone diminished the cytokine-induced increase in nitrite, iNOS by immunocytochemistry, and iNOS mRNA. These data demonstrate that cytokines, such as those released by mononuclear cells, can induce lung epithelial iNOS expression and NO release, and that this is attenuated by dexamethasone.

  16. Galangin Abrogates Ovalbumin-Induced Airway Inflammation via Negative Regulation of NF-κB.

    PubMed

    Zha, Wang-Jian; Qian, Yan; Shen, Yi; Du, Qiang; Chen, Fei-Fei; Wu, Zhen-Zhen; Li, Xiao; Huang, Mao

    2013-01-01

    Persistent activation of nuclear factor κB (NF-κB) has been associated with the development of asthma. Galangin, the active pharmacological ingredient from Alpinia galanga, is reported to have a variety of anti-inflammatory properties in vitro via negative regulation of NF-κB. This study aimed to investigate whether galangin can abrogate ovalbumin- (OVA-) induced airway inflammation by negative regulation of NF-κB. BALB/c mice sensitized and challenged with OVA developed airway hyperresponsiveness (AHR) and inflammation. Galangin dose dependently inhibited OVA-induced increases in total cell counts, eosinophil counts, and interleukin-(IL-) 4, IL-5, and IL-13 levels in bronchoalveolar lavage fluid, and reduced serum level of OVA-specific IgE. Galangin also attenuated AHR, reduced eosinophil infiltration and goblet cell hyperplasia, and reduced expression of inducible nitric oxide synthase and vascular cell adhesion protein-1 (VCAM-1) levels in lung tissue. Additionally, galangin blocked inhibitor of κB degradation, phosphorylation of the p65 subunit of NF-κB, and p65 nuclear translocation from lung tissues of OVA-sensitized mice. Similarly, in normal human airway smooth muscle cells, galangin blocked tumor necrosis factor-α induced p65 nuclear translocation and expression of monocyte chemoattractant protein-1, eotaxin, CXCL10, and VCAM-1. These results suggest that galangin can attenuate ovalbumin-induced airway inflammation by inhibiting the NF-κB pathway.

  17. 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

  18. 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

  19. Generation of Pig Airways using Rules Developed from the Measurements of Physical Airways

    PubMed Central

    Azad, Md Khurshidul; Mansy, Hansen A.

    2017-01-01

    Background A method for generating bronchial tree would be helpful when constructing models of the tree for benchtop experiments as well as for numerical modeling of flow or sound propagation in the airways. Early studies documented the geometric details of the human airways that were used to develop methods for generating human airway tree. However, methods for generating animal airway tree are scarcer. Earlier studies suggested that the morphology of animal airways can be significantly different from that of humans. Hence, using algorithms for the human airways may not be accurate in generating models of animal airway geometry. Objective The objective of this study is to develop an algorithm for generating pig airway tree based on the geometric details extracted from the physical measurements. Methods In the current study, measured values of branch diameters, lengths and bifurcation angles and rotation of bifurcating planes were used to develop an algorithm that is capable of generating a realistic pig airway tree. Results The generation relations between parent and daughter branches were found to follow certain trends. The diameters and the length of different branches were dependent on airway generations while the bifurcation angles were primarily dependent on bifurcation plane rotations. These relations were sufficient to develop rules for generating a model of the pig large airways. Conclusion The results suggested that the airway tree generated from the algorithm can provide an approximate geometric model of pig airways for computational and benchtop studies. PMID:28255517

  20. Generation of Pig Airways using Rules Developed from the Measurements of Physical Airways.

    PubMed

    Azad, Md Khurshidul; Mansy, Hansen A

    2016-09-01

    A method for generating bronchial tree would be helpful when constructing models of the tree for benchtop experiments as well as for numerical modeling of flow or sound propagation in the airways. Early studies documented the geometric details of the human airways that were used to develop methods for generating human airway tree. However, methods for generating animal airway tree are scarcer. Earlier studies suggested that the morphology of animal airways can be significantly different from that of humans. Hence, using algorithms for the human airways may not be accurate in generating models of animal airway geometry. The objective of this study is to develop an algorithm for generating pig airway tree based on the geometric details extracted from the physical measurements. In the current study, measured values of branch diameters, lengths and bifurcation angles and rotation of bifurcating planes were used to develop an algorithm that is capable of generating a realistic pig airway tree. The generation relations between parent and daughter branches were found to follow certain trends. The diameters and the length of different branches were dependent on airway generations while the bifurcation angles were primarily dependent on bifurcation plane rotations. These relations were sufficient to develop rules for generating a model of the pig large airways. The results suggested that the airway tree generated from the algorithm can provide an approximate geometric model of pig airways for computational and benchtop studies.

  1. Comparison of fractional exhaled nitric oxide levels in chronic obstructive pulmonary disease, bronchial asthma and healthy subjects of Nepal.

    PubMed

    Shrestha, Sanjeet Krishna; Shrestha, Sanjeev; Sharma, Lucky; Pant, Subash; Neopane, Arpana

    2017-09-13

    Fractional exhaled nitric oxide levels in exhaled breath can indicate ongoing eosinophilic airway inflammation, specifically in asthma. But its utility is being explored for central airway inflammations, including chronic obstructive pulmonary disease. Normal levels of fractional exhaled nitric oxide (FENO50) have been defined in different studies but not in Nepal. This study compares FENO50 levels in normal subjects, asthma and chronic obstructive pulmonary disease. Single breath estimation of FENO50 was measured by a handheld electrochemical sensor-based device in normal non-smoking adults (n = 106), clinically controlled asthma (n = 106) and stable chronic obstructive pulmonary disease (n = 106). The geometric mean for FENO50 was 14 parts per billion (ppb) with a median of 16 ppb, first quartile at 11 ppb and third quartile at 20 ppb in normal non-smoking adults. The values were 31 ppb (geometric mean), 34 ppb (median), 17 ppb (first quartile) and 79 ppb (third quartile) in clinically controlled asthma. Similarly the values were 10 ppb (geometric mean), 11 ppb (median), 6 ppb (first quartile) and 17 ppb (third quartile) in stable chronic obstructive airway disease. The log-transformed data showed significantly higher FENO50 levels in the asthma group compared with the normal (p < 0.001) and chronic obstructive airway disease (p < 0.001). However, levels were similar between healthy and chronic obstructive airway disease groups (p = 0.08). FENO50 levels were higher in bronchial asthma (despite disease control) than in normal non-smoking adults and subjects with stable chronic obstructive pulmonary disease. Levels of FENO50 were similar between the chronic obstructive airway disease and normal groups.

  2. Recent trends in airway management

    PubMed Central

    Karlik, Joelle; Aziz, Michael

    2017-01-01

    Tracheal intubation remains a life-saving procedure that is typically not difficult for experienced providers in routine conditions. Unfortunately, difficult intubation remains challenging to predict and intubation conditions may make the event life threatening. Recent technological advances aim to further improve the ease, speed, safety, and success of intubation but have not been fully investigated. Video laryngoscopy, though proven effective in the difficult airway, may result in different intubation success rates in various settings and in different providers’ hands. The rescue surgical airway remains a rarely used but critical skill, and research continues to investigate optimal techniques. This review highlights some of the new thoughts and research on these important topics. PMID:28299194

  3. Analysis of Notch Signaling-Dependent Gene Expression in Developing Airways Reveals Diversity of Clara Cells

    PubMed Central

    Guha, Arjun; Vasconcelos, Michelle; Zhao, Rui; Gower, Adam C.; Rajagopal, Jayaraj; Cardoso, Wellington V.

    2014-01-01

    Clara cells (CCs) are a morphologically and operationally heterogeneous population of Secretoglobin Scgb1a1-expressing secretory cells that are crucial for airway homeostasis and post-injury repair. Analysis of the extent and origin of CC diversity are limited by knowledge of genes expressed in these cells and their precursors. To identify novel putative markers of CCs and explore the origins of CC diversity, we characterized global changes in gene expression in embryonic lungs in which CCs do not form due to conditional disruption of Notch signaling (RbpjkCNULL). Microarray profiling, Real Time PCR (qRT-PCR), and RNA in situ hybridization (ISH) identified eleven genes downregulated in the E18.5 airways of Rbpjkcnull compared to controls, nearly half not previously known to mark CCs. ISH revealed that several genes had overlapping but distinct domains of expression of in the normal developing lung (E18.5). Notably, Reg3g, Chad, Gabrp and Lrrc26 were enriched in proximal airways, Hp in the distal airways and Upk3a in clusters of cells surrounding Neuroepithelial Bodies (NEBs). Seven of the eleven genes, including Reg3g, Hp, and Upk3a, were expressed in the adult lung in CCs in a pattern similar to that observed in the developing airways. qRT-PCR-based analysis of gene expression of CCs isolated from different airway regions of B1-EGFP reporter mice corroborated the spatial enrichment in gene expression observed by ISH. Our study identifies candidate markers for CC-precursors and CCs and supports the idea that the diversification of the CC phenotype occurs already during embryonic development. PMID:24586412

  4. Daily exhaled nitric oxide measurements and asthma exacerbations in children.

    PubMed

    van der Valk, R J P; Baraldi, E; Stern, G; Frey, U; de Jongste, J C

    2012-02-01

    Fractional exhaled Nitric Oxide (FeNO) is a biomarker for eosinophilic airway inflammation and can be measured at home on a daily basis. A short-term increase in FeNO may indicate a higher risk of future asthma exacerbations. To assess changes in FeNO before and after asthma exacerbations compared to a stable control period. A post hoc analysis was performed on daily FeNO measurements over 30 weeks in children with asthma (n = 77). Moderate exacerbations were defined by an increase in symptom scores and severe exacerbations by prescription of prednisone. Individual mean and maximum FeNO, the variability of FeNO assessed by the coefficient of variation (CV), and slopes of FeNO in time were all quantified in 3-week blocks. Cross-correlation of FeNO with symptoms and autocorrelation of FeNO were assessed in relation to exacerbations and examined as predictors for exacerbations compared to reference periods using logistic regression. Fractional exhaled nitric oxide could be assessed in relation to 25 moderate and 12 severe exacerbations. The CV, slope, cross-correlation, and autocorrelation of daily FeNO increased before moderate exacerbations. Increases in slope were also randomly seen in 19% of 2-week blocks of children without exacerbations. At least 3-5 FeNO measurements in the 3 weeks before an exacerbation were needed to calculate a slope that could predict moderate exacerbations. No specific pattern of FeNO was seen before severe exacerbations. Fractional exhaled nitric oxide monitoring revealed changes in FeNO prior to moderate exacerbations. Whether this can be used to prevent loss of asthma control should be further explored. © 2011 John Wiley & Sons A/S.

  5. Airway inflammation in thunderstorm asthma.

    PubMed

    Wark, P A B; Simpson, J; Hensley, M J; Gibson, P G

    2002-12-01

    Epidemics of acute asthma associated with thunderstorms occur intermittently worldwide, though airway inflammation during these acute episodes has not been characterized. The aim of this study was to characterize airway inflammation in thunderstorm asthma. Cases were recruited after presentation to the emergency room with acute asthma immediately following a thunderstorm (n = 6). They were compared to two control groups: a group of atopic asthmatics that had presented with acute asthma to the emergency room prior to the thunderstorm (n = 12), and a second group of corticosteroid naive asthmatics who presented to the emergency room in the prior 12 months (n = 6). Subjects had spirometry, sputum induction and allergy skin tests acutely and at review 4 weeks later. Thunderstorm (TS) cases were more likely to have a history of hay fever and grass pollen allergy, and less likely to be on inhaled corticosteroids (ICS) prior to presentation. Cases and control groups had a similar degree of moderate to severe acute airway obstruction (P = 1.0). TS cases had elevated sputum eosinophils (14.8% of total cell count) compared to controls (1%, 2.6%, P < 0.01). TS cases had higher sputum eosinophil cationic protein (ECP; 11,686 ng/mL) compared to controls (1,883, 3,300, P = 0.02) acutely. TS cases had more cells positive for IL-5 (30%) compared to controls (1, 1.5%, P = 0.02). When adjusted for ICS use, TS cases had a risk ratio for elevated sputum eosinophils of 2.4 (1.23-4.69). Thunderstorm asthma is characterized by airway inflammation with IL-5-mediated sputum eosinophilia and eosinophil degranulation. These results are consistent with allergen exposure as the cause of the exacerbation, and are consistent with the thunderstorm-induced grass pollen deluge as the cause of epidemic asthma after thunderstorms.

  6. To characterize the incidence of airway misplacement of nasogastric tubes in anesthetized intubated patients by using a manometer technique.

    PubMed

    Hsieh, Shao-Wei; Chen, Hung-Shu; Chen, Yi-Ting; Hung, Kuo-Chuan

    2017-04-01

    This study characterized the incidence of airway misplacement of nasogastric (NG) tubes in surgical patients, and the benefit of using a manometer to discriminate gastric placement from airway placement of NG tubes. Subjects included adult patients scheduled for abdominal surgery. After tracheal intubation, a 16 Fr. NG tube was inserted blindly through the nostril, and its position was assessed using the auscultation (10-ml air insufflation) or manometer (attached to NG tubes) techniques. Briefly, a biphasic pressure change synchronous with airway pressure during mechanical ventilation indicated airway misplacement. The presence of a notable pressure change while compressing the epigastric area indicated a gastric placement. A surgeon made the final confirmation of NG tube placement within the stomach using manual palpation of the tube immediately after laparotomy. The first-attempt success rate was 82.7 % in 104 patients. There were 29 misplacements of 130 attempted insertions (oral cavity, n = 23; trachea, n = 3; distal esophagus, n = 3). The incidence of airway misplacement was 2.9 % (3 of 104 cases). For confirmation of gastric placement, the auscultation technique had a sensitivity of 100.0 % and a specificity of 79.3 %. In contrast, the manometer technique had a sensitivity of 100.0 % and a specificity of 100.0 % in the discrimination of gastric placement from airway placement of NG tubes. Airway misplacement of NG tubes is not uncommon in surgical patients, and the manometer technique may be a reliable and safe method to discriminate gastric placement from airway placement of NG tubes.

  7. Ozone-induced airway epithelial cell death, the neurokinin-1 receptor pathway, and the postnatal developing lung

    PubMed Central

    Murphy, Shannon R.; Oslund, Karen L.; Hyde, Dallas M.; Miller, Lisa A.; Van Winkle, Laura S.

    2014-01-01

    Children are uniquely susceptible to ozone because airway and lung growth continue for an extensive period after birth. Early-life exposure of the rhesus monkey to repeated ozone cycles results in region-specific disrupted airway/lung growth, but the mediators and mechanisms are poorly understood. Substance P (SP), neurokinin-1 receptor (NK-1R); and nuclear receptor Nur77 (NR4A1) are signaling pathway components involved in ozone-induced cell death. We hypothesize that acute ozone (AO) exposure during postnatal airway development disrupts SP/NK-1R/Nur77 pathway expression and that these changes correlate with increased ozone-induced cell death. Our objectives were to 1) spatially define the normal development of the SP/NK-1R/Nur77 pathway in conducting airways; 2) compare how postnatal age modulates responses to AO exposure; and 3) determine how concomitant, episodic ozone exposure modifies age-specific acute responses. Male infant rhesus monkeys were assigned at age 1 mo to two age groups, 2 or 6 mo, and then to one of three exposure subgroups: filtered air (FA), FA+AO (AO: 8 h/day × 2 days), or episodic biweekly ozone exposure cycles (EAO: 8 h/day × 5 days/14-day cycle+AO). O3 = 0.5 ppm. We found that 1) ozone increases SP/NK-1R/Nur77 pathway expression in conducting airways, 2) an ozone exposure cycle (5 days/cycle) delivered early at age 2 mo resulted in an airway that was hypersensitive to AO exposure at the end of 2 mo, and 3) continued episodic exposure (11 cycles) resulted in an airway that was hyposensitive to AO exposure at 6 mo. These observations collectively associate with greater overall inflammation and epithelial cell death, particularly in early postnatal (2 mo), distal airways. PMID:25063800

  8. The effects of short-term fish oil supplementation on pulmonary function and airway inflammation following a high-fat meal.

    PubMed

    Ade, Carl J; Rosenkranz, S K; Harms, C A

    2014-04-01

    Many environmental and dietary influences can cause immune cells to produce biological mediators that increase airway inflammation. A high-fat meal (HFM) is one stimulus that increases airway inflammation in healthy individuals. Supplementation with omega-3 fatty acids can reduce inflammation systemically and may be beneficial to the airways. To determine if omega-3 fatty acid supplementation via fish oil would mitigate the airway inflammatory response induced by a single HFM. Seventeen non-asthmatic men (22 ± 2 years.) were supplemented with 3,000 mg × day(-1) fish oil or a placebo for 3 weeks. Fractional exhaled nitric oxide (FENO; a marker of airway inflammation), impulse oscillometry (a measure of respiratory impedance), pulmonary function, and triglycerides were measured prior to and 2 h following a HFM. Following a HFM, triglycerides increased in both fish oil and placebo groups compared to pre-HFM (~59 and ~49 %, respectively, p < 0.05). The percent increase in FENO was greater in the placebo group compared to the fish oil group (25.7 ± 16.7 vs. -1.99 ± 10.5 %, respectively, p < 0.05). A significant correlation was observed between blood triglycerides and FENO in the placebo group (r = 0.61; p < 0.05), but not the fish oil group (p = 0.21). A single HFM increases airway inflammation and omega-3 fatty acid supplementation via fish oil protects against HFM associated changes in airway health.

  9. Management of distal humeral coronal shear fractures

    PubMed Central

    Yari, Shahram S; Bowers, Nathan L; Craig, Miguel A; Reichel, Lee M

    2015-01-01

    Coronal shear fractures of the distal humerus are rare, complex fractures that can be technically challenging to manage. They usually result from a low-energy fall and direct compression of the distal humerus by the radial head in a hyper-extended or semi-flexed elbow or from spontaneous reduction of a posterolateral subluxation or dislocation. Due to the small number of soft tissue attachments at this site, almost all of these fractures are displaced. The incidence of distal humeral coronal shear fractures is higher among women because of the higher rate of osteoporosis in women and the difference in carrying angle between men and women. Distal humeral coronal shear fractures may occur in isolation, may be part of a complex elbow injury, or may be associated with injuries proximal or distal to the elbow. An associated lateral collateral ligament injury is seen in up to 40% and an associated radial head fracture is seen in up to 30% of these fractures. Given the complex nature of distal humeral coronal shear fractures, there is preference for operative management. Operative fixation leads to stable anatomic reduction, restores articular congruity, and allows initiation of early range-of-motion movements in the majority of cases. Several surgical exposure and fixation techniques are available to reconstruct the articular surface following distal humeral coronal shear fractures. The lateral extensile approach and fixation with countersunk headless compression screws placed in an anterior-to-posterior fashion are commonly used. We have found a two-incision approach (direct anterior and lateral) that results in less soft tissue dissection and better outcomes than the lateral extensile approach in our experience. Stiffness, pain, articular incongruity, arthritis, and ulnohumeral instability may result if reduction is non-anatomic or if fixation fails. PMID:25984515

  10. 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.

  11. Clinical application of exhaled nitric oxide measurement in pediatric lung diseases

    PubMed Central

    2012-01-01

    Summary Fractional exhaled nitric oxide (FeNO) is a non invasive method for assessing the inflammatory status of children with airway disease. Different ways to measure FeNO levels are currently available. The possibility of measuring FeNO levels in an office setting even in young children, and the commercial availability of portable devices, support the routine use of FeNO determination in the daily pediatric practice. Although many confounding factors may affect its measurement, FeNO is now widely used in the management of children with asthma, and seems to provide significantly higher diagnostic accuracy than lung function or bronchial challenge tests. The role of FeNO in airway infection (e.g. viral bronchiolitis and common acquired pneumonia), in bronchiectasis, or in cases with diffuse lung disease is less clear. This review focuses on the most recent advances and the current clinical applications of FeNO measurement in pediatric lung disease. PMID:23273317

  12. Exhaled nasal nitric oxide during humming: potential clinical tool in sinonasal disease?

    PubMed

    Maniscalco, Mauro; Pelaia, Girolamo; Sofia, Matteo

    2013-04-01

    The use of nasal nitric oxide (nNO) in sinonasal disease has recently been advocated as a potential tool to explore upper inflammatory airway disease. However, it is currently hampered by some factors including the wide range of measurement methods, the presence of various confounding factors and the heterogeneity of the study population. The contribution of nasal airway and paranasal sinuses communicating with the nose through the ostia represents the main confounding factor. There is accumulating evidence that nasal humming (which is the production of a tone without opening the lips or forming words) during nNO measurement increases nNO levels due to a rapid gas exchange in the paranasal sinuses. The aim of this review is to discuss the basic concepts and clinical applications of nNO assessment during humming, which represents a simple and noninvasive method to approach sinonasal disease.

  13. 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

  14. Nitric oxide in health and disease from the point of view of the otorhinolaryngologist.

    PubMed

    Selimoglu, Erol

    2005-01-01

    Nitric oxide (NO) plays role in a great range of important functions in the organism, such as vasodilatation, relaxation of muscles, neurotransmission, neuromediation, and host defense reactions. In the upper airways, nasal cavities and paranasal sinuses are the main sources of this biological mediator. Although the exact role of NO in nasal physiology remains poorly understood, the functions are thought to be host defense, ciliary motility and improved ventilation-perfusion ratio in the lungs by auto-inhalation. Low NO concentrations were reported in certain diseases such as primary ciliary dyskinesia, cystic fibrosis, and acute and chronic maxillary sinusitis whereas high concentrations were detected in upper airway infection, allergic rhinitis and nasal polyposis. Additionally this ubiquitous radical is being implicated in the regulation of cochlear blood flow, sensorineural hearing loss, middle ear effusions, and outer hair cell and vestibular functions. Solid tumors is another area where NO appears to have both tumor-promoting and tumor-inhibiting effects. The presence of NO with high levels within the nose and paranasal sinuses makes it reasonable to believe that this pluripotent gas is involved in a variety of physiological as well as pathophysiological events in the airways. Although NO has an ever-increasing role in various areas related to the practice of otolaryngology, further research is required to understand fully the role of NO in the upper airways.

  15. Bronchoconstriction and endogenous nitric oxide in isolated lungs of spontaneously hypertensive rats.

    PubMed

    Kwasniewski, Fábio H; Landgraf, Richardt Gama; Bakhle, Yeshwant S; Jancar, Sonia

    2004-03-19

    Bronchoconstrictor responses were measured in lungs isolated from spontaneously hypertensive (SHR) and normotensive rats, perfused via the airways. Lungs from SHRs were more responsive than lungs from normotensive rats to methacholine, 5-hydroxytryptamine (5-HT), arachidonic acid or prostaglandin H(2). The responses of SHR airways to methacholine or 5-HT were unaffected by pretreatment in vivo with an inhibitor of nitric oxide (NO) synthase, N(omega)-nitro-L-arginine methyl ester hydrochloride (L-NAME, 30 mg kg(-1)), although responses in normotensive airways to methacholine, but not to 5-HT, were enhanced. Antigen challenge of isolated lungs from actively sensitized rats elicited bronchoconstriction, not different between strains. Pretreatment with L-NAME increased the response to antigen challenge only in normotensive lungs. Compound 48/80 induced bronchoconstriction in lungs from either strain, equally. These responses to compound 48/80 were unaffected by L-NAME pretreatment. Thus, SHR airways lack relaxing factors and degranulation of mast cells in SHR lungs was not affected by endogenous NO.

  16. A patient with a de novo distal 22q11.2 microdeletion and anxiety disorder.

    PubMed

    Verhoeven, Willem; Egger, Jos; Brunner, Han; de Leeuw, Nicole

    2011-02-01

    We report on a young female with normal intelligence evaluated for long-term anxiety. Her history includes prematurity, neonatal feeding problems, surgical correction of congenital heart defects, recurrent upper airway and urinary tract infections, and delayed motor and developmental milestones. Physical examination disclosed small stature and minor dysmorphisms. Chromosome analysis, 22q11.2 FISH analysis, and subtelomeric MLPA testing did not detect any abnormalities. Genome wide SNP Array analysis showed a de novo deletion in 22q11.21q11.22, the so-called distal 22q11 microdeletion that involves the MAPK1 gene. A diagnosis of panic disorder was made and the patient was successfully treated with a daily dose of 20 mg citalopram. To our knowledge, this is the first adolescent patient with a long history of complaints about anxiety and a distal 22q11 microdeletion. We speculate that genes from the deleted region, especially MAPK1, increase the neurobiological susceptibility to anxiety disorders that may be a part of the psychopathological phenotype of the distal 22q11.2 microdeletion syndrome. Copyright © 2010 Wiley-Liss, Inc.

  17. Nitric oxide and the paranasal sinuses.

    PubMed

    Lundberg, Jon O

    2008-11-01

    The discovery within the paranasal sinuses for the production of nitric oxide (NO) has altered the traditional explanations of sinus physiology. This review article reports the ongoing investigation of sinus physiology beginning with the discovery of NO gas production in the paranasal sinuses that occurred in 1995, and the impact that finding has had both in the basic science and clinical arenas. It was shown that healthy paranasal sinus epithelium expresses an inducible NO synthase that continuously generates large amounts of NO, a pluripotent gaseous messenger with potent vasodilating, and antimicrobial activity. This NO can be measured noninvasively in nasally exhaled breath. The role of NO in the sinuses is likely to enhance local host defense mechanisms via direct inhibition of pathogen growth and stimulation of mucociliary activity. The NO concentration in a healthy sinus exceeds those that are needed for antibacterial effects in vitro. In patients with primary ciliary dyskinesia (PCD) and in cystic fibrosis, nasal NO is extremely low. This defect NO generation likely contributes to the great susceptibility to chronic sinusitis in these patients. In addition, the low-nasal NO is of diagnostic value especially in PCD, where nasal NO is very low or absent. Intriguingly, NO gas from the nose and sinuses is inhaled with every breath and reaches the lungs in a more diluted form to enhance pulmonary oxygen uptake via local vasodilation. In this sense NO may be regarded as an "aerocrine" hormone that is produced in the nose and sinuses and transported to a distal site of action with every inhalation. Copyright 2008 Wiley-Liss, Inc.

  18. Airway Assessment for Office Sedation/Anesthesia

    PubMed Central

    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

  19. Sextant of Sapphires for Molar Distalization

    PubMed Central

    Palla, Yudistar Venkata; Ganugapanta, Vivek Reddy

    2016-01-01

    Introduction Space analysis quantifies the amount of crowding within the arches estimating the severity of space discrepancy. The space gaining procedures include extraction and non-extraction procedures like expansion, proximal stripping and molar distalization. Aim To identify features seen in molar distalization cases. Materials and Methods The sample size comprised 20 patients in whom molar distalization was decided as the treatment plan. The study models and lateral cephalograms of all the patients were taken. Occlusograms were obtained. Model analysis and cephalometric analysis were performed. Descriptive statistical analysis like mean, standard deviation, standard error and mode were done. Results The parameters in Question gave following results. The Bolton analysis showed anterior mandibular excess with mean value of 1.56mm±1.07. The first order discrepancy between maxillary central and lateral incisors was 5±1.95. The premolar rotation showed mean value of 16.58±5.12. The molar rotation showed the value of 7.66±2.26. The nasolabial angle showed the mean of 101.25±8.7 IMPA of 101.4±5.74. Conclusion The six features studied in molar distalization cases [First order discrepancy between upper central and lateral incisors; Rotation of premolars and molars; Bolton’s discrepancy in anterior dentition; Average to horizontal growth pattern; Proclined lower incisors and Obtuse nasolabial angle] can be taken as patterns seen in molar distalization cases and considered as a valid treatment plan. PMID:27656572

  20. Sextant of Sapphires for Molar Distalization.

    PubMed

    Ponnada, Swaroopa Rani; Palla, Yudistar Venkata; Ganugapanta, Vivek Reddy

    2016-08-01

    Space analysis quantifies the amount of crowding within the arches estimating the severity of space discrepancy. The space gaining procedures include extraction and non-extraction procedures like expansion, proximal stripping and molar distalization. To identify features seen in molar distalization cases. The sample size comprised 20 patients in whom molar distalization was decided as the treatment plan. The study models and lateral cephalograms of all the patients were taken. Occlusograms were obtained. Model analysis and cephalometric analysis were performed. Descriptive statistical analysis like mean, standard deviation, standard error and mode were done. The parameters in Question gave following results. The Bolton analysis showed anterior mandibular excess with mean value of 1.56mm±1.07. The first order discrepancy between maxillary central and lateral incisors was 5±1.95. The premolar rotation showed mean value of 16.58±5.12. The molar rotation showed the value of 7.66±2.26. The nasolabial angle showed the mean of 101.25±8.7 IMPA of 101.4±5.74. The six features studied in molar distalization cases [First order discrepancy between upper central and lateral incisors; Rotation of premolars and molars; Bolton's discrepancy in anterior dentition; Average to horizontal growth pattern; Proclined lower incisors and Obtuse nasolabial angle] can be taken as patterns seen in molar distalization cases and considered as a valid treatment plan.

  1. Dietary Nitrate Acutely and Markedly Increased Exhaled Nitric Oxide in a Cystic Fibrosis Case

    PubMed Central

    Kerley, Conor P.; Kilbride, Emma; Greally, Peter; Elnazir, Basil

    2016-01-01

    Airway nitric oxide (NO) is a ubiquitous signaling molecule with bronchoprotective, anti-inflammatory and anti-infective roles. Cystic fibrosis (CF) is a chronic lung condition associated with deceased exhaled NO. Strategies to increase exhaled NO in CF have yielded inconsistent results. A potential new method of increasing systemic NO involves ingestion of dietary, inorganic nitrate which is reduced to nitrite and NO. We present the case of a 12-year-old, athletic boy with CF who demonstrated acute but marked increases in exhaled NO following dietary nitrate consumption compared to placebo PMID:27630187

  2. Measurement of exhaled nitric oxide concentration in patients with obstructive sleep apnea

    PubMed Central

    Zhang, Dongmei; Luo, Jinmei; Qiao, Yixian; Xiao, Yi; Huang, Rong; Zhong, Xu

    2017-01-01

    Abstract Background: Exhaled nitric oxide (eNO) has been proposed as a noninvasive measure of airway inflammation. However, its value in patients with obstructive sleep apnea (OSA) is still controversial. The authors aim to assess the difference in eNO levels between patients with OSA and controls by a meta-analysis. Methods: A systematic search was performed in the PubMed, EMBASE, the Cochrane Library, and MEDLINE databases to collect relevant studies published from 1996 to 2016. Eligible studies that reported eNO levels in patients with OSA were included. STATA (version 12.0) was used for data analysis. Results: Two hundred eighty-four studies were reviewed for inclusion, with 16 studies pooled for analysis (16 studies for fractional exhaled nitric oxide [FENO], 5 for alveolar nitric oxide [CANO], and 4 for the maximum airway wall flux of nitric oxide [J′awNO]). The FENO levels were significantly higher in patients with OSA compared with that in the control groups (6.32 ppb, 95% confidence interval [CI] 4.46–8.33, P < 0.001). Furthermore, FENO was significantly increased (4.00 ppb, 95% CI 1.74–6.27, P = 0.001) after overnight sleep in patients with OSA, but not in healthy controls. Additionally, long-term continuous positive airway pressure (CPAP) therapy reduced FENO levels (−5.82 ppb, 95% CI −9.6 to −2.01, P < 0.001). However, the CANO (−0.01 ppb, 95% CI −1.66 to 1.64, P = 0.989) and J’awNO levels (220.32 pl/s, 95% CI −49.31 to 489.94, P = 0.109) were not significantly different between the OSA groups and non-OSA groups. Conclusion: The results of the meta-analysis suggest that OSA is significantly associated with airway inflammation and elevated FENO levels can be modified by long-term CPAP therapy. J’awNO and CANO levels were not significantly different between the OSA groups and control groups. PMID:28328850

  3. Automated Lobe-Based Airway Labeling

    PubMed Central

    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

  4. Method for 3D Airway Topology Extraction

    PubMed Central

    Grothausmann, Roman; Kellner, Manuela; Heidrich, Marko; Lorbeer, Raoul-Amadeus; Ripken, Tammo; Meyer, Heiko; Kuehnel, Mark P.; Ochs, Matthias; Rosenhahn, Bodo

    2015-01-01

    In lungs the number of conducting airway generations as well as bifurcation patterns varies across species and shows specific characteristics relating to illnesses or gene variations. A method to characterize the topology of the mouse airway tree using scanning laser optical tomography (SLOT) tomograms is presented in this paper. It is used to test discrimination between two types of mice based on detected differences in their conducting airway pattern. Based on segmentations of the airways in these tomograms, the main spanning tree of the volume skeleton is computed. The resulting graph structure is used to distinguish between wild type and surfactant protein (SP-D) deficient knock-out mice. PMID:25767561

  5. Resolution of cell-mediated airways diseases

    PubMed Central

    2010-01-01

    "Inflammation resolution" has of late become a topical research area. Activation of resolution phase mechanisms, involving select post-transcriptional regulons, transcription factors, 'autacoids', and cell phenotypes, is now considered to resolve inflammatory diseases. Critical to this discourse on resolution is the elimination of inflammatory cells through apoptosis and phagocytosis. For major inflammatory diseases such as asthma and COPD we propose an alternative path to apoptosis for cell elimination. We argue that transepithelial migration of airway wall leukocytes, followed by mucociliary clearance, efficiently and non-injuriously eliminates pro-inflammatory cells from diseased airway tissues. First, it seems clear that numerous infiltrated granulocytes and lymphocytes can be speedily transmitted into the airway lumen without harming the epithelial barrier. Then there are a wide range of 'unexpected' findings demonstrating that clinical improvement of asthma and COPD is not only associated with decreasing numbers of airway wall inflammatory cells but also with increasing numbers of these cells in the airway lumen. Finally, effects of inhibition of transepithelial migration support the present hypothesis. Airway inflammatory processes have thus been much aggravated when transepithelial exit of leukocytes has been inhibited. In conclusion, the present hypothesis highlights risks involved in drug-induced inhibition of transepithelial migration of airway wall leukocytes. It helps interpretation of common airway lumen data, and suggests approaches to treat cell-mediated airway inflammation. PMID:20540713

  6. 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.

  7. Use of a Novel Airway Kit and Simulation in Resident Training on Emergent Pediatric Airways.

    PubMed

    Melzer, Jonathan M; Hamersley, Erin R S; Gallagher, Thomas Q

    2017-06-01

    Objective Development of a novel pediatric airway kit and implementation with simulation to improve resident response to emergencies with the goal of improving patient safety. Methods Prospective study with 9 otolaryngology residents (postgraduate years 1-5) from our tertiary care institution. Nine simulated pediatric emergency airway drills were carried out with the existing system and a novel portable airway kit. Response times and time to successful airway control were noted with both the extant airway system and the new handheld kit. Results were analyzed to ensure parametric data and compared with t tests. A Bonferroni adjustment indicated that an alpha of 0.025 was needed for significance. Results Use of the airway kit significantly reduced the mean time of resident arrival by 47% ( P = .013) and mean time of successful intubation by 50% ( P = .007). Survey data indicated 100% improved resident comfort with emergent airway scenarios with use of the kit. Discussion Times to response and meaningful intervention were significantly reduced with implementation of the handheld airway kit. Use of simulation training to implement the new kit improved residents' comfort and airway skills. This study describes an affordable novel mobile airway kit and demonstrates its ability to improve response times. Implications for Practice The low cost of this airway kit makes it a tenable option even for smaller hospitals. Simulation provides a safe and effective way to familiarize oneself with novel equipment, and, when possible, realistic emergent airway simulations should be used to improve provider performance.

  8. Topographic matching of distal radius and proximal fibula articular surface for distal radius osteoarticular reconstruction.

    PubMed

    Zhang, H; Chen, S; Wang, Z; Guo, Y; Liu, B; Tong, D

    2016-07-01

    During osteoarticular reconstruction of the distal radius with the proximal fibula, congruity between the two articular surfaces is an important factor in determining the quality of the outcome. In this study, a three-dimensional model and a coordinate transformation algorithm were developed on computed tomography scanning. Articular surface matching was performed and parameters for the optimal position were determined quantitatively. The mean radii of best-fit spheres of the articular surfaces of the distal radius and proximal fibula were compared quantitatively. The radial inclination and volar tilt following reconstruction by an ipsilateral fibula graft, rather than the contralateral, best resembles the values of the native distal radius. Additionally, the ipsilateral fibula graft reconstructed a larger proportion of the distal radius articular surface than did the contralateral. The ipsilateral proximal fibula graft provides a better match for the reconstruction of the distal radius articular surface than the contralateral, and the optimal position for graft placement is quantitatively determined.

  9. Parasympathetic Control of Airway Submucosal Glands: Central Reflexes and the Airway Intrinsic Nervous System

    PubMed Central

    Wine, Jeffrey J.

    2007-01-01

    Airway submucosal glands produce the mucus that lines the upper airways to protect them against insults. This review summarizes evidence for two forms of gland secretion, and hypothesizes that each is mediated by different but partially overlapping neural pathways. Airway innate defense comprises low level gland secretion, mucociliary clearance and surveillance by airway-resident phagocytes to keep the airways sterile in spite of nearly continuous inhalation of low levels of pathogens. Gland secretion serving innate defense is hypothesized to be under the control of intrinsic (peripheral) airway neurons and local reflexes, and these may depend disproportionately on non-cholinergic mechanisms, with most secretion being produced by VIP and tachykinins. In the genetic disease cystic fibrosis, airway glands no longer secrete in response to VIP alone and fail to show the synergy between VIP, tachykinins and ACh that is observed in normal glands. The consequent crippling of the submucosal gland contribution to innate defense may be one reason that cystic fibrosis airways are infected by mucus-resident bacteria and fungi that are routinely cleared from normal airways. By contrast, the acute (emergency) airway defense reflex is centrally mediated by vagal pathways, is primarily cholinergic, and stimulates copious volumes of gland mucus in response to acute, intense challenges to the airways, such as those produced by very vigorous exercise or aspiration of foreign material. In cystic fibrosis, the acute airway defense reflex can still stimulate the glands to secrete large amounts of mucus, although its properties are altered. Importantly, treatments that recruit components of the acute reflex, such as inhalation of hypertonic saline, are beneficial in treating cystic fibrosis airway disease. The situation for recipients of lung transplants is the reverse; transplanted airways retain the airway intrinsic nervous system but lose centrally mediated reflexes. The consequences

  10. Fabrication and Evaluation of a Noncompliant Molar Distalizing Appliance: Bonded Molar Distalizer

    PubMed Central

    Sodagar, A.; Ahmad Akhoundi, M. S.; Rafighii, A.; Arab, S.

    2011-01-01

    Objective Attempts to treat class II malocclusions without extraction in non-compliant patients have led to utilization of intraoral molar distalizing appliances. The purpose of this study was to investigate dental and skeletal effects of Bonded Molar Distalizer (BMD) which is a simple molar distalizing appliance. Materials and Methods Sixteen patients (12 girls, four boys) with bilateral half-cusp class II molar relationship, erupted permanent second molars and normal or vertical growth pattern were selected for bilateral distalization of maxillary molars via BMD. The screws were activated every other day, alternately. Lateral cephalograms and study models were obtained before treatment and after 11 weeks activation of the appliance. Results Significant amounts of molar distalization, molar distal tipping and anchorage loss were observed. The mean maxillary first molar distal movement was 1.22±0.936 mm with a distal tipping of 2.97±3.74 degrees in 11 weeks. The rate of distal movement was 0.48 mm per month. Reciprocal mesial movement of the first premolars was 2.26±1.12 mm with a mesial tipping of 4.25±3.12 degrees. Maxillary incisors moved 3.55±1.46 mm and tipped 9.87±5.03 degrees mesially. Lower anterior face height (LAFH) decreased 1.28±1.36 mm. Conclusion BMD is appropriate for distalizing maxillary molars, especially in patients with critical LAFH, although significant amounts of anchorage loss occur using this appliance. PMID:22457837

  11. Osteochondritis of the Distal Tibial Epiphysis

    PubMed Central

    EL Hajj, Firass; Sebaaly, Amer; Kharrat, Khalil; Ghanem, Ismat

    2012-01-01

    Osteochondritis of the distal tibial epiphysis is a very rare entity. 9 cases have been described in 7 articles and 8 other cases have been mentioned in textbooks. This paper describes the 10th case of osteochondritis of the distal tibial epiphysis and summarizes the clinical and radiological presentations of the 9 other cases. The etiology of this entity is well debated in the literature. We believe that it results from a vascular abnormality in the distal tibial epiphysis associated with a mechanical stress (trauma, excessive overload, etc.). Since it is a self-limited disease, the prognosis is good and the younger the patient is the better the prognosis will be. In general, this entity responds well to conservative treatment. PMID:23193412

  12. Physeal arrest of the distal radius.

    PubMed

    Abzug, Joshua M; Little, Kevin; Kozin, Scott H

    2014-06-01

    Fractures of the distal radius are among the most common pediatric fractures. Although most of these fractures heal without complication, some result in partial or complete physeal arrest. The risk of physeal arrest can be reduced by avoiding known risk factors during fracture management, including multiple attempts at fracture reduction. Athletes may place substantial compressive and shear forces across the distal radial physes, making them prone to growth arrest. Timely recognition of physeal arrest can allow for more predictable procedures to be performed, such as distal ulnar epiphysiodesis. In cases of partial arrest, physeal bar excision with interposition grafting can be performed. Once ulnar abutment is present, more invasive procedures may be required, including ulnar shortening osteotomy or radial lengthening.

  13. Operative treatment of distal radius fractures.

    PubMed

    Vasenius, J

    2008-01-01

    The incidence of distal radius fractures is increasing together with the average age of population. Intra-articular incongruity is the most probable cause of unsatisfactory outcome of distal radius fractures in younger and more active patients. Thus, the main goal in the treatment of distal radius fractures should be restoration of articular congruence. A computed tomography (CT) is recommended to help surgeon in preoperative planning in the treatment of comminuted intra-articular fractures. New implants have been designed to provide stable enough fixation for early mobilisation after surgery and to lower rather high complication rates related to conventional fixation methods such as external fixation and dorsal plating. The most common complications related to volar fixed angle plating such as flexor and extensor tendon problems, median nerve neuropathy, and screw diplacement into the radiocarpal joint are surgeon related and are avoidable with proper education. More randomized prospective studies are needed to prove superiority of any fixation method to another.

  14. Treatment of obstructive sleep apnoea leads to enhanced pulmonary vascular nitric oxide release.

    PubMed

    Lattimore, Jo-Dee L; Wilcox, Ian; Adams, Mark R; Kilian, Jens G; Celermajer, David S

    2008-05-23

    Obstructive sleep apnoea (OSA) is associated with pulmonary hypertension, however neither the pathogenesis of pulmonary vascular disease nor the effect of successful treatment of OSA on pulmonary vascular physiology has been characterised. Seven subjects aged 52 (range 36-63) years with moderate to severe obstructive sleep apnoea (apnoea-hypopnoea index>15/h) had detailed pulmonary vascular reactivity studies, before and after 3 months of successful treatment with nasal continuous positive airways pressure (CPAP). On both occasions, we measured pulmonary pressure, flow velocity, flow and resistance, at baseline and in response to acetylcholine (an endothelium-dependent dilator), sodium nitroprusside (an endothelium-independent dilator), l-NMMA (an antagonist of nitric oxide synthesis) and l-Arginine (the substrate of nitric oxide). At baseline, pulmonary flow increased in response to acetylcholine and nitroprusside and fell in response to l-NMMA. Following CPAP treatment, the decrease in flow to l-NMMA was significantly greater (to 62+/-6% of control value vs 85+/-6% of pre-treatment; p=0.01), consistent with enhanced basal release of nitric oxide. The acetylcholine response tended to be greater after treatment (174+/-26% of control vs 147+/-12% of pre-CPAP, p=0.22), however the nitroprusside response was unchanged. Successful treatment of obstructive sleep apnoeic episodes in sleep results in enhanced nitric oxide release by the pulmonary microvascular circulation.

  15. Modeling of the Nitric Oxide Transport in the Human Lungs

    PubMed Central

    Karamaoun, Cyril; Van Muylem, Alain; Haut, Benoît

    2016-01-01

    In the human lungs, nitric oxide (NO) acts as a bronchodilatator, by relaxing the bronchial smooth muscles and is closely linked to the inflammatory status of the lungs, owing to its antimicrobial activity. Furthermore, the molar fraction of NO in the exhaled air has been shown to be higher for asthmatic patients than for healthy patients. Multiple models have been developed in order to characterize the NO dynamics in the lungs, owing to their complex structure. Indeed, direct measurements in the lungs are difficult and, therefore, these models are valuable tools to interpret experimental data. In this work, a new model of the NO transport in the human lungs is proposed. It belongs to the family of the morphological models and is based on the morphometric model of Weibel (1963). When compared to models published previously, its main new features are the layered representation of the wall of the airways and the possibility to simulate the influence of bronchoconstriction (BC) and of the presence of mucus on the NO transport in lungs. The model is based on a geometrical description of the lungs, at rest and during a respiratory cycle, coupled with transport equations, written in the layers composing an airway wall and in the lumen of the airways. First, it is checked that the model is able to reproduce experimental information available in the literature. Second, the model is used to discuss some features of the NO transport in healthy and unhealthy lungs. The simulation results are analyzed, especially when BC has occurred in the lungs. For instance, it is shown that BC can have a significant influence on the NO transport in the tissues composing an airway wall. It is also shown that the relation between BC and the molar fraction of NO in the exhaled air is complex. Indeed, BC might lead to an increase or to a decrease of this molar fraction, depending on the extent of the BC and on the possible presence of mucus. This should be confirmed experimentally and might

  16. Remote sensing of nitric oxide emissions from planes, trains and automobiles

    NASA Astrophysics Data System (ADS)

    Popp, Peter John

    Remote sensing has been proven as an effective method for measuring in-use mobile source emissions. This document describes the development of a remote sensor for mobile source nitric oxide, based on an instrument previously developed at the University of Denver for measuring carbon monoxide and hydrocarbon emissions. The new remote sensor makes use of a high-speed ultraviolet spectrometer to quantify nitric oxide by absorption spectroscopy at 226 nm in the ultraviolet region. The high-speed spectrometer is coupled to an existing FEAT remote sensor, for the simultaneous measurement of CO, CO2 and hydrocarbons by non-dispersive infrared absorption spectroscopy. The utility of the instrument was demonstrated in the measurement of nitric oxide emissions from automobiles, commercial aircraft, and railroad locomotives. The remote sensor was used to measure nitric oxide emissions from motor vehicles in Chicago in 1997 and 1998, as part of a five-year study to characterize motor vehicle emissions and deterioration in that city. Emissions data were collected for over 19,000 vehicles in 1997 and almost 23,000 vehicles in 1998. All of these records contained valid measurements for carbon monoxide and hydrocarbons, in addition to nitric oxide. In September of 1997, a study was conducted with the cooperation of British Airways and the British Airports Authority to demonstrate the capability of the remote sensor in measuring nitric oxide emissions from in-use commercial aircraft. In two days of sampling at London Heathrow Airport, a total of 122 measurements were made of 90 different aircraft, ranging in size from Gulfstream executive jets to Boeing 747-400s. The measured nitric oxide emission indices were not inconsistent with commercial aircraft emission indices published by the International Civil Aviation Organization. The utility of the remote sensor in measuring nitric oxide emissions from railroad locomotives was demonstrated in January of 1999, in a study conducted with

  17. Recent advances in distal tubular potassium handling

    PubMed Central

    Rodan, Aylin R.; Cheng, Chih-Jen

    2011-01-01

    It is well known that sodium reabsorption and aldosterone play important roles in potassium secretion by the aldosterone-sensitive distal nephron. Sodium- and aldosterone-independent mechanisms also exist. This review focuses on some recent studies that provide novel insights into the sodium- and aldosterone-independent potassium secretion by the aldosterone-sensitive distal nephron. In addition, we discuss a study reporting on the regulation of the mammalian potassium kidney channel ROMK by intracellular and extracellular magnesium, which may be important in the pathogenesis of persistent hypokalemia in patients with concomitant potassium and magnesium deficiency. We also discuss outstanding questions and propose working models for future investigation. PMID:21270092

  18. Torsion of wandering spleen and distal pancreas

    SciTech Connect

    Sheflin, J.R.; Lee, C.M.; Kretchmar, K.A.

    1984-01-01

    Wandering spleen is the term applied to the condition in which a long pedicle allows the spleen to lie in an abnormal location. Torsion of a wandering spleen is an unusual cause of an acute abdomen and is rarely diagnosed preoperatively. Associated torsion of the distal pancreas is even more uncommon. The authors describe a patient with torsion of a wandering spleen and distal pancreas, who was correctly diagnosed, and define the merits of the imaging methods used. The initial examination should be /sup 99//sup m/Tc-sulfur colloid liner-spleen scanning.

  19. Distal Humerus Fractures: Open Reduction Internal Fixation.

    PubMed

    Mighell, Mark A; Stephens, Brent; Stone, Geoffrey P; Cottrell, Benjamin J

    2015-11-01

    Distal humerus fractures are challenging injuries for the upper extremity surgeon. However, recent techniques in open reduction internal fixation have been powerful tools in getting positive outcomes. To get such results, the surgeon must be aware of how to properly use these techniques in their respective practices. The method of fixation depends on the fracture, taking the degree of comminution and the restoration of the columns and articular surface into account. This article helps surgeons understand the concepts behind open reduction internal fixation of the distal humerus and makes them aware of pitfalls that may lead to negative results. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Contemporary Management of Primary Distal Urethral Cancer.

    PubMed

    Traboulsi, Samer L; Witjes, Johannes Alfred; Kassouf, Wassim

    2016-11-01

    Primary urethral cancer is one of the rare urologic tumors. Distal urethral tumors are usually less advanced at diagnosis compared with proximal tumors and have a good prognosis if treated appropriately. Low-stage distal tumors can be managed successfully with a surgical approach in men or radiation therapy in women. There are no clear-cut indications for the choice of the most appropriate treatment modality. Organ-preserving modalities have shown effective and should be used whenever they do not compromise the oncological safety to decrease the physical and psychological trauma of dismemberment or loss of sexual/urinary function.

  1. Distal Femur Locking Plate: The Answer to All Distal Femoral Fractures

    PubMed Central

    Garg, Sudhir Kumar; Gupta, Parmanand; Jangira, Vivek; Singh, Jagdeep; Rana, Sudhir

    2016-01-01

    Introduction Good results have been published by researchers with distal femur nail, dynamic condylar screw and even addition of a medial plate to a distal femur locking plate for treating distal femur fractures. By this study, we explore the capability of a distal femur locking plate to counter distal femur fractures of extra- articular, partial or intra- articular nature. Positive results have been published by various groups from all over the world. Aim To study the functional and radiological outcome of distal femoral fractures in skeletally mature patients treated by open reduction and internal fixation with distal femur locking plate. Materials and Methods This was a prospective study conducted from January 2012 to March 2014 at the Government Medical College and Hospital (GMCH) with a 2 year follow-up. Twenty five skeletally mature patients with post-traumatic distal femur fractures were included. Patients with open grade 3B and 3C distal femur fractures, according to the Gustilo- Anderson classification and pathological distal femur fractures were excluded from the study. Patients with any fracture other than the distal femur in the ipsilateral limb were excluded from the study. Follow-up at 3 months, 6 months, 1 year and 2 years was carried out and evaluation was done according to the Neer scoring system. The statistical data analysis was carried out using SPSS version 20 (IBM, Chicago, USA). The p-value <0.05 was considered significant. Results Following all principles of fracture reduction, union was achieved in all patients with mean time to radiological union being 19 weeks. The mean Range of Motion (ROM) was 109 degrees with 20 patients having a Neer score graded as excellent to satisfactory. Our study had nine cases which required additional surgeries. Out of these, all nine cases required bone grafting, three also required antibiotic cement bead insertion initially. Three patients developed complications in the form of infection (two cases) and mal

  2. Reconstruction of the Distal Oblique Bundle of the Interosseous Membrane: A Technique to Restore Distal Radioulnar Joint Stability.

    PubMed

    Riggenbach, Michael D; Wright, Thomas W; Dell, Paul C

    2015-11-01

    The distal radioulnar ligament reconstruction is a technique that may be used for distal radioulnar joint instability without arthritis and failed nonsurgical management; clinical results demonstrate resolved or improved stability. Recent literature has focused on the distal oblique bundle of the interosseous membrane and its contributions to stability. This article describes a technically simple surgical technique to reconstruct the distal oblique bundle and restore distal radioulnar joint stability.

  3. Air pollution and airway disease.

    PubMed

    Kelly, F J; Fussell, J C

    2011-08-01

    Epidemiological and toxicological research continues to support a link between urban air pollution and an increased incidence and/or severity of airway disease. Detrimental effects of ozone (O(3)), nitrogen dioxide (NO(2)) and particulate matter (PM), as well as traffic-related pollution as a whole, on respiratory symptoms and function are well documented. Not only do we have strong epidemiological evidence of a relationship between air pollution and exacerbation of asthma and respiratory morbidity and mortality in patients with chronic obstructive pulmonary disease (COPD), but recent studies, particularly in urban areas, have suggested a role for pollutants in the development of both asthma and COPD. Similarly, while prevalence and severity of atopic conditions appear to be more common in urban compared with rural communities, evidence is emerging that traffic-related pollutants may contribute to the development of allergy. Furthermore, numerous epidemiological and experimental studies suggest an association between exposure to NO(2) , O(3) , PM and combustion products of biomass fuels and an increased susceptibility to and morbidity from respiratory infection. Given the considerable contribution that traffic emissions make to urban air pollution researchers have sought to characterize the relative toxicity of traffic-related PM pollutants. Recent advances in mechanisms implicated in the association of air pollutants and airway disease include epigenetic alteration of genes by combustion-related pollutants and how polymorphisms in genes involved in antioxidant pathways and airway inflammation can modify responses to air pollution exposures. Other interesting epidemiological observations related to increased host susceptibility include a possible link between chronic PM exposure during childhood and vulnerability to COPD in adulthood, and that infants subjected to higher prenatal levels of air pollution may be at greater risk of developing respiratory conditions

  4. Airway management: induced tension pneumoperitoneum

    PubMed Central

    Ahmed, Khedher; Amine, El Ghali Mohamed; Abdelbaki, Azouzi; Jihene, Ayachi; Khaoula, Meddeb; Yamina, Hamdaoui; Mohamed, Boussarsar

    2016-01-01

    Pneumoperitoneum is not always associated with hollow viscus perforation. Such condition is called non-surgical or spontaneous pneumoperitoneum. Intrathoracic causes remain the most frequently reported mechanism inducing this potentially life threatening complication. This clinical condition is associated with therapeutic dilemma. We report a case of a massive isolated pneumoperitoneum causing acute abdominal hypertension syndrome, in a 75 year female, which occurred after difficult airway management and mechanical ventilation. Emergent laparotomy yielded to full recovery. The recognition of such cases for whom surgical management can be avoided is primordial to avoid unnecessary laparotomy and its associated morbidity particularly in the critically ill.

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

    PubMed

    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

    2007-05-01

    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.

  6. Setipiprant, a selective CRTH2 antagonist, reduces allergen-induced airway responses in allergic asthmatics.

    PubMed

    Diamant, Z; Sidharta, P N; Singh, D; O'Connor, B J; Zuiker, R; Leaker, B R; Silkey, M; Dingemanse, J

    2014-08-01

    CRTH2 is a G-protein-coupled receptor on T helper2 cells that mediates pro-inflammatory effects of prostaglandin D2 in allergic responses. To investigate the tolerability and pharmacokinetics of setipiprant (ACT-129968), a selective orally active CRTH2 antagonist, in allergic asthmatics and to assess the protective effects of multiple doses of this drug against allergen-induced airway responses. In this 3-centre, double-blinded, placebo-controlled, cross-over study, 18 allergic asthmatic males were randomized to setipiprant 1000 mg or matching placebo b.i.d. for 5 consecutive days. Study periods were separated by a washout of ≥ 3 weeks. On study day 4, subjects underwent a standardized allergen challenge and airway response was recorded by FEV1 until 10 h post-allergen. Airway responsiveness to methacholine and exhaled nitric oxide (eNO) were measured pre- and post-dosing. The effects of both treatments on the allergen-induced airway responses were compared by a paired Student's t-test. Fifteen subjects completed the study per-protocol and were included in the analysis. Overall, setipiprant was well tolerated and no clinically relevant adverse events occurred. Trough plasma concentrations showed a high inter-subject variability. Compared with placebo, setipiprant significantly reduced the allergen-induced late asthmatic response (LAR), inhibiting the area under the response vs. time curve (AUC(3-10 h) ) by on average 25.6% (P = 0.006) and significantly protected against the allergen-induced airway hyperresponsiveness (AHR) to methacholine (P = 0.0029). There was no difference in the early asthmatic response (EAR) or in allergen-induced changes in eNO between treatments. Setipiprant at multiple oral doses was well tolerated and reduced both the allergen-induced LAR and the associated AHR in allergic asthmatics. Our findings confirm that CRTH2 may be a promising target for the treatment of allergic disorders. © 2014 John Wiley & Sons Ltd.

  7. Mechanisms of inflammation-mediated airway smooth muscle plasticity and airways remodeling in asthma.

    PubMed

    Halayko, Andrew J; Amrani, Yassine

    2003-09-16

    Recent evidence points to progressive structural change in the airway wall, driven by chronic local inflammation, as a fundamental component for development of irreversible airway hyperresponsiveness. Acute and chronic inflammation is orchestrated by cytokines from recruited inflammatory cells, airway myofibroblasts and myocytes. Airway myocytes exhibit functional plasticity in their capacity for contraction, proliferation, and synthesis of matrix protein and cytokines. This confers a principal role in driving different components of the airway remodeling process, and mediating constrictor hyperresponsiveness. Functional plasticity of airway smooth muscle (ASM) is regulated by an array of environmental cues, including cytokines, which mediate their effects through receptors and a number of intracellular signaling pathways. Despite numerous studies of the cellular effects of cytokines on cultured airway myocytes, few have identified how intracellular signaling pathways modulate or induce these cellular responses. This review summarizes current understanding of these concepts and presents a model for the effects of inflammatory mediators on functional plasticity of ASM in asthma.

  8. Comparative evaluation of molar distalization therapy using pendulum and distal screw appliances

    PubMed Central

    Cafagna, Alessandra; Fontana, Mattia; Cozzani, Mauro

    2015-01-01

    Objective To compare dentoalveolar and skeletal changes produced by the pendulum appliance (PA) and the distal screw appliance (DS) in Class II patients. Methods Forty-three patients (19 men, 24 women) with Class II malocclusion were retrospectively selected for the study. Twenty-four patients (mean age, 12.2 ± 1.5 years) were treated with the PA, and 19 patients (mean age, 11.3 ± 1.9 years) were treated with the DS. The mean distalization time was 7 months for the PA group and 9 months for the DS group. Lateral cephalograms were obtained at T1, before treatment, and at T2, the end of distalization. A Mann-Whitney U test was used for statistical comparisons of the two groups between T1 and T2. Results PA and DS were equally effective in distalizing maxillary molars (4.7 mm and 4.2 mm, respectively) between T1 and T2; however, the maxillary first molars showed less distal tipping in the DS group than in the PA group (3.2° vs. 9.0°, respectively). Moreover, significant premolar anchorage loss (2.7 mm) and incisor proclination (5.0°) were noted in the PA group, whereas premolar distal movement (1.9 mm) and no significant changes at the incisor (0.1°) were observed in the DS group. No significant sagittal or vertical skeletal changes were detected between the two groups during the distalization phase. Conclusions PA and DS seem to be equally effective in distalizing maxillary molars; however, greater distal molar tipping and premolar anchorage loss can be expected using PA. PMID:26258063

  9. [Nitric oxide production in plants].

    PubMed

    Małolepsza, Urszula

    2007-01-01

    There are still many controversial observations and opinions on the cellular/subcellular localization and sources of endogenous nitric oxide synthesis in plant cells. NO can be produced in plants by non-enzymatic and enzymatic systems depending on plant species, organ or tissue as well as on physiological state of the plant and changing environmental conditions. The best documented reactions in plant that contribute to NO production are NO production from nitrite as a substrate by cytosolic (cNR) and membrane bound (PM-NR) nitrate reductases (NR), and NO production by several arginine-dependent nitric oxide synthase-like activities (NOS). The latest papers indicate that mitochondria are an important source of arginine- and nitrite-dependent NO production in plants. There are other potential enzymatic sources of NO in plants including xanthine oxidoreductase, peroxidase, cytochrome P450.

  10. Diagnostic tools assessing airway remodelling in asthma.

    PubMed

    Manso, L; Reche, M; Padial, M A; Valbuena, T; Pascual, C

    2012-01-01

    Asthma is an inflammatory disease of the lower airways characterised by the presence of airway inflammation, reversible airflow obstruction and airway hyperresponsiveness and alterations on the normal structure of the airways, known as remodelling. Remodelling is characterised by the presence of metaplasia of mucous glands, thickening of the lamina reticularis, increased angiogenesis, subepithelial fibrosis and smooth muscle hypertrophy/hyperplasia. Several techniques are being optimised at present to achieve a suitable diagnosis for remodelling. Diagnostic tools could be divided into two groups, namely invasive and non-invasive methods. Invasive techniques bring us information about bronchial structural alterations, obtaining this information directly from pathological tissue, and permit measure histological modification placed in bronchi layers as well as inflammatory and fibrotic cell infiltration. Non-invasive techniques were developed to reduce invasive methods disadvantages and measure airway remodelling-related markers such as cytokines, inflammatory mediators and others. An exhaustive review of diagnostic tools used to analyse airway remodelling in asthma, including the most useful and usually employed methods, as well as the principal advantages and disadvantages of each of them, bring us concrete and summarised information about all techniques used to evaluate alterations on the structure of the airways. A deep knowledge of these diagnostic tools will make an early diagnosis of airway remodelling possible and, probably, early diagnosis will play an important role in the near future of asthma. Copyright © 2011 SEICAP. Published by Elsevier Espana. All rights reserved.

  11. 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…

  12. Upper airway resistance: species-related differences.

    PubMed

    Kirschvink, N; Reinhold, P

    2010-07-01

    In veterinary medicine, upper airway resistance deserves a particular attention in equines athletes and brachycephalic dogs. Due to the anatomical peculiarities of the upper airway and/or pathological conditions, significant alterations of performance and/or well being might occur in horses and dogs. Physiological specificities and pathological changes of the lower respiratory tract deserve a major attention in other species.

  13. 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 ...

  14. 21 CFR 868.5110 - Oropharyngeal airway.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 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....

  15. 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....

  16. 21 CFR 868.5110 - Oropharyngeal airway.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 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. (a...

  17. 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. (a...

  18. 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

  19. Nitric oxide reburning with methane

    SciTech Connect

    Kumpaty, S.K.; Subramanian, K.

    1996-12-31

    This paper deals with initial findings from the ongoing, three-year DOE program that began on 02/01/1995. The program involves computer simulation studies to aid in planning and conducting a series of experiments that will extend the knowledge of reburning process. The objective of this work is to find nitric oxide reduction effectiveness for various reburning fuels and identify both homogeneous and heterogeneous reaction mechanisms characterizing NO reduction.

  20. Alternative to Nitric Acid Passivation

    NASA Technical Reports Server (NTRS)

    Kessel, Kurt R.

    2016-01-01

    Corrosion is an extensive problem that affects the National Aeronautics and Space Administration (NASA) and European Space Agency (ESA). The deleterious effects of corrosion result in steep costs, asset downtime affecting mission readiness, and safety risks to personnel. It is vital to reduce corrosion costs and risks in a sustainable manner. The primary objective of this effort is to qualify citric acid as an environmentally-preferable alternative to nitric acid for passivation of stainless steel alloys.

  1. Nitric Oxide Production in Plants

    PubMed Central

    Planchet, Elisabeth

    2006-01-01

    There is now general agreement that nitric oxide (NO) is an important and almost universal signal in plants. Nevertheless, there are still many controversial observations and opinions on the importance and function of NO in plants. Partly, this may be due to the difficulties in detecting and even more in quantifying NO. Here, we summarize major pathways of NO production in plants, and briefly discuss some methodical problems. PMID:19521475

  2. Distally based dorsalis pedis island flap for a distal lateral electric burn of the big toe.

    PubMed

    Governa, M; Barisoni, D

    1996-12-01

    Reconstruction of the small defects in the distal portion of the foot has always represented a difficult problem. A case of a young man with a deep electric burn of the distal lateral side of the big toe successfully treated with a distally based dorsalis pedis island flap based on the first dorsal metatarsal artery (FDMA) is presented. The donor site area of the dorsum of the foot was grafted, and deambulation was reassumed 3 weeks later. Advantages; limits and anatomical consideration regarding the viability of the flap are also discussed.

  3. Double Plating of Distal Fibula Fractures.

    PubMed

    Vance, Danica D; Vosseller, J Turner

    2017-02-01

    Distal fibula fractures are common orthopaedic injuries that often require open reduction internal fixation (ORIF) to anatomically reduce the fracture and minimize the risk of posttraumatic arthritis. In certain clinical situations, stouter fixation may be advantageous to decrease the risk of fixation failure. In this study, the authors report on 12 patients who underwent distal fibula ORIF with 2 one-third tubular plates. Twelve consecutive patients who underwent distal fibula ORIF with 2 one-third tubular plates were retrospectively reviewed. Clinical and radiographic outcomes were reviewed, and functional outcomes were obtained using the Foot and Ankle Outcome Score (FAOS). Institutional review board approval was obtained. All 12 fractures healed clinically and radiographically. One patient was lost to follow-up after healing of the fracture. One patient had removal of fibular hardware at 15 months after surgery. Ten patients had no hardware related pain and good ankle function. FAOS scores were obtained at a mean of 25.6 months after surgery and were as follows: pain (87.6, SD = 9.5), activities of daily living (90.4, SD = 14.5), symptoms (93.3, SD = 9.5), sports (89.5, SD = 18.1), and quality of life (57.4, SD = 21.3). Double plating of distal fibula fractures is a viable technique for problem fractures that potentially provides a readily accessible, low-cost alternative to other means of enhancing fixation. Level IV.

  4. A New Distal Radioulnar Joint Prosthesis

    PubMed Central

    Schuurman, Arnold H.

    2013-01-01

    Pain and instability of the distal radioulnar joint (DRUJ) are common sequelae following a fracture of the distal radius. Many soft tissue procedures have been described, not all of which are successful. Ulnar head replacement prostheses are available but do not always provide stability. We designed a two-part, easy to implant, distal radioulnar prosthesis and implanted it in 19 patients. The first prototype was inserted in 2002 and is still in place. During the study, the design was changed twice, resulting in three groups with four patients in group A, five in group B, and ten in group C. Unfortunately all five prostheses in group B had to be removed because of loosening, while only two prostheses in group C had to be removed, for nonprosthetic reasons. For the 12 patients who retained their prosthesis, forearm function increased while grip strength increased significantly. Pain scores decreased and the Disabilities of the Arm, Shoulder, and Hand (DASH) score improved but remained high. We conclude that the prosthesis offers a new treatment option for ulnar instability following distal ulnar resection. PMID:24436843

  5. Arthroscopic Arthrodesis of the Distal Tibiofibular Syndesmosis.

    PubMed

    Lui, Tun Hing

    2015-01-01

    Chronic syndesmosis disruption can occur if an acute lesion is missed or inadequately managed. This can result in significant functional deficit and development of post-traumatic ankle arthritis. Anatomic reduction of the syndesmosis and maintenance of the reduction by syndesmotic screw fixation alone, ligamentous reconstruction, or fusion of the syndesmosis are recommended. A technique of arthroscopic distal tibiofibular syndesmosis arthrodesis is described.

  6. Difficult airway response team: a novel quality improvement program for managing hospital-wide airway emergencies.

    PubMed

    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

    2015-07-01

    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. 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 3 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. 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 or current tracheostomy. Twenty

  7. 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

  8. The critical airway in adults: The facts

    PubMed Central

    Bonanno, Fabrizio Giuseppe

    2012-01-01

    An algorithm on the indications and timing for a surgical airway in emergency as such cannot be drawn due to the multiplicity of variables and the inapplicability in the context of life-threatening critical emergency, where human brain elaborates decisions better in cluster rather than in binary fashion. In particular, in emergency or urgent scenarios, there is no clear or established consensus as to specifically who should receive a tracheostomy as a life-saving procedure; and more importantly, when. The two classical indications for emergency tracheostomy (laryngeal injury and failure to secure airway with endotracheal intubation or cricothyroidotomy) are too generic and encompass a broad spectrum of possibilities. In literature, specific indications for emergency tracheostomy are scattered and are biased, partially comprehensive, not clearly described or not homogeneously gathered. The review highlights the indications and timing for an emergency surgical airway and gives recommendations on which surgical airway method to use in critical airway. PMID:22787346

  9. Airway fires during surgery: Management and prevention.

    PubMed

    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.

  10. Airway pressure release ventilation: theory and practice.

    PubMed

    Frawley, P M; Habashi, N M

    2001-05-01

    Airway pressure release ventilation (APRV) is a relatively new mode of ventilation, that only became commercially available in the United States in the mid-1990s. Airway pressure release ventilation produces tidal ventilation using a method that differs from any other mode. It uses a release of airway pressure from an elevated baseline to simulate expiration. The elevated baseline facilitates oxygenation, and the timed releases aid in carbon dioxide removal. Advantages of APRV include lower airway pressures, lower minute ventilation, minimal adverse effects on cardio-circulatory function, ability to spontaneously breathe throughout the entire ventilatory cycle, decreased sedation use, and near elimination of neuromuscular blockade. Airway pressure release ventilation is consistent with lung protection strategies that strive to limit lung injury associated with mechanical ventilation. Future research will probably support the use of APRV as the primary mode of choice for patients with acute lung injury.

  11. Barrier function of airway tract epithelium

    PubMed Central

    Ganesan, Shyamala; Comstock, Adam T; Sajjan, Uma S

    2013-01-01

    Airway epithelium contributes significantly to the barrier function of airway tract. Mucociliary escalator, intercellular apical junctional complexes which regulate paracellular permeability and antimicrobial peptides secreted by the airway epithelial cells are the three primary components of barrier function of airway tract. These three components act cooperatively to clear inhaled pathogens, allergens and particulate matter without inducing inflammation and maintain tissue homeostasis. Therefore impairment of one or more of these essential components of barrier function may increase susceptibility to infection and promote exaggerated and prolonged innate immune responses to environmental factors including allergens and pathogens resulting in chronic inflammation. Here we review the regulation of components of barrier function with respect to chronic airways diseases. PMID:24665407

  12. 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. Copyright © 2016. Published by Elsevier Inc.

  13. Toll-like receptors and airway inflammation.

    PubMed

    Gon, Yasuhiro

    2008-03-01

    The respiratory tract opens to the external environment at the oral side edge, and the other edge of the respiratory tract connects to the closed space (alveoli), and so to preserve the sterility in the terminal respiratory tract is critical for protection against pathogens. The recognition machinery for the invasion of microbes is indispensable for the preservation of the sterility in the lungs. Our general understanding of how microbes are recognized by the innate immune system has increased considerably over the past several years, and the contribution of Toll-Like Receptors (TLRs) to innate immunity is now well documented. In the meantime, it has come to understand that many inflammatory processes may depend on TLR signaling, it has been considered to be involved in the pathogenesis of airway inflammatory diseases such as airway infections, bronchial asthma, and occupational airway diseases. In this review, we focus on physiological roles of TLRs in defense mechanisms of the airways, and pathophysiological roles on airway diseases.

  14. IL-1β expression in the distal lung epithelium disrupts lung morphogenesis and epithelial cell differentiation in fetal mice.

    PubMed

    Hogmalm, Anna; Bry, Maija; Strandvik, Birgitta; Bry, Kristina

    2014-01-01

    Perinatal inflammation and the inflammatory cytokine IL-1 can modify lung morphogenesis. To examine the effects of antenatal expression of IL-1β in the distal airway epithelium on fetal lung morphogenesis, we studied lung development and surfactant expression in fetal mice expressing human IL-1β under the control of the surfactant protein (SP)-C promoter. IL-1β-expressing pups suffered respiratory failure and died shortly after birth. IL-1β caused fetal lung inflammation and enhanced the expression of keratinocyte-derived chemokine (KC/CXCL1) and monocyte chemoattractant protein 3 (MCP-3/CCL7), the calgranulins S100A8 and S100A9, the acute-phase protein serum amyloid A3, the chitinase-like proteins Ym1 and Ym2, and pendrin. IL-1β decreased the percentage of the total distal lung area made up of air saccules and the number of air saccules in the lungs of fetal mice. IL-1β inhibited the expression of VEGF-A and its receptors VEGFR-1 and VEGFR-2. The percentage of the cellular area of the distal lung made up of capillaries was decreased in IL-1β-expressing fetal mice. IL-1β suppressed the production of SP-B and pro-SP-C and decreased the amount of phosphatidylcholine and the percentage of palmitic acid in the phosphatidylcholine fraction of lung phospholipids, indicating that IL-1β prevented the differentiation of type II epithelial cells. The production of Clara cell secretory protein in the nonciliated bronchiolar (Clara) cells was likewise suppressed by IL-1β. In conclusion, expression of IL-1β in the epithelium of the distal airways disrupted the development of the airspaces and capillaries in the fetal lung and caused fatal respiratory failure at birth.

  15. Characterization of exhaled nitric oxide: introducing a new reproducible method for nasal nitric oxide measurements.

    PubMed

    Palm, J P; Graf, P; Lundberg, J O; Alving, K

    2000-08-01

    Nitric oxide (NO) is present in the human nasal airways and has been suggested to originate primarily from the paranasal sinuses. The aim of this study was to establish a new and reproducible method for measurement of nasal NO. Through repeated single-breath measurements the intra- and inter-individual variations of NO levels in nasally (into a tightly fitting mask covering the nose) and orally exhaled air were determined in healthy humans. Variations due to the methods used were investigated. The contribution of oral NO to the nasal exhalations by introducing a mouthwash procedure was also studied. This study shows distinct individual values of NO in nasally and orally exhaled air of healthy humans. Some diurnal variability was also found with a rise in NO in nasally and orally exhaled air over the day, but no, or little, day-to-day variability when comparing the results from separate mornings. There was no correlation between NO levels in nasally and orally exhaled air, whereas there was a strong correlation between NO levels in air exhaled through the left and right nostril. The levels of NO in air exhaled at 0.17 L x s(-1) through either nostril separately were higher than in air exhaled at the same flow rate through both nostrils simultaneously. After the introduction of a mouthwash procedure the level of NO in orally, but not nasally exhaled air was reduced. To conclude the method using nasal exhalation into a nose mask is highly reproducible. It is also suggested that subtracting the level of NO in orally exhaled air, after mouthwash, from that in nasally exhaled air, would adequately reflect nasal NO levels.

  16. Eosinophilic airway inflammation is increased in children with asthma and food allergies.

    PubMed

    Kulkarni, Neeta; Ragazzo, Vincenzo; Costella, Silvia; Piacentini, Giorgio; Boner, Attilio; O'Callaghan, Christopher; Fiocchi, Alessandro; Kantar, Ahmad

    2012-02-01

    Asthma is associated with food allergies in a significant number of children, with evidence linking allergies to asthma severity and morbidity. In this study, we tested our hypothesis that the eosinophilic lower airway inflammation is higher in asthmatic children with food allergies. The aims of the study were to compare the eosinophilic inflammatory markers in asthmatic children with and without food allergies. Children with asthma, with (n = 22) and (n = 53) without food allergies were included. All subjects were classified according to the GINA guidelines (2009) and had received at least 3 months of anti-inflammatory therapy prior to testing. Fractional exhaled nitric oxide and sputum differential counts were performed using standard techniques.   Children with asthma and food allergies had significantly higher fractional exhaled nitric oxide median (range) [(22.4 (6.1-86.9) vs. 10.3 (2.7-38.7) (p = 0.01)] and sputum eosinophil percentage [15.5 (5.0-53.0) vs. 2.0 (0-20) (p < 0.001)] compared with asthmatic children without allergies. These results suggest that the children with asthma and food allergies have increased eosinophilic inflammation of the airways. © 2011 John Wiley & Sons A/S.

  17. Targeting Pulmonary Endothelial Hemoglobin α Improves Nitric Oxide Signaling and Reverses Pulmonary Artery Endothelial Dysfunction.

    PubMed

    Alvarez, Roger A; Miller, Megan P; Hahn, Scott A; Galley, Joseph C; Bauer, Eileen; Bachman, Timothy; Hu, Jian; Sembrat, John; Goncharov, Dmitry; Mora, Ana L; Rojas, Mauricio; Goncharova, Elena; Straub, Adam C

    2017-08-11

    Pulmonary hypertension is characterized by pulmonary endothelial dysfunction. Previous work showed that systemic artery endothelial cells express hemoglobin α to control nitric oxide diffusion, but the role of this system in the pulmonary circulation has not been evaluated. We hypothesize that up-regulation of hemoglobin α in pulmonary endothelial cells contributes to nitric oxide depletion and pulmonary vascular dysfunction in pulmonary hypertension. Co-cultures of human pulmonary microvascular endothelial cells and distal pulmonary arterial vascular smooth muscle cells, lung tissue from control and pulmonary hypertensive lungs, and a mouse model of chronic hypoxia-induced pulmonary hypertension were used. Immunohistochemical, immunoblot analyses, spectrophotometry, and blood vessel myography experiments were performed in this study. We find increased expression of hemoglobin α in pulmonary endothelium from humans and mice with pulmonary hypertension compared to controls. In addition, we show up-regulation of hemoglobin α in human pulmonary endothelial cells co-cultured with pulmonary artery smooth muscle cells in hypoxia. We treated pulmonary endothelial cells with a hemoglobin α mimetic peptide that disrupts the association of hemoglobin α with endothelial nitric oxide synthase, and found that cells treated with the peptide exhibited increased nitric oxide signaling compared to a scrambled peptide. Myography experiments using pulmonary arteries from hypoxic mice show that the hemoglobin α mimetic peptide enhanced vasodilation in response to acetylcholine. Our findings reveal that endothelial hemoglobin α functions as an endogenous scavenger of nitric oxide in the pulmonary endothelium. Targeting this pathway may offer a novel therapeutic target to increase endogenous levels of nitric oxide in pulmonary hypertension.

  18. 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

  19. 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.

  20. Formoterol and salbutamol inhibit bradykinin- and histamine-induced airway microvascular leakage in guinea-pig.

    PubMed Central

    Advenier, C.; Qian, Y.; Koune, J. D.; Molimard, M.; Candenas, M. L.; Naline, E.

    1992-01-01

    1. The effects of the beta 2-adrenoceptor agonists, salbutamol and formoterol, on the increase of microvascular permeability induced by histamine or bradykinin in guinea-pig airways have been studied in vivo. Extravasation of intravenously injected Evans blue dye was used as an index of permeability. The effects of salbutamol and formoterol on the increase in pulmonary airway resistance induced by histamine or bradykinin have also been studied. 2. The increase in pulmonary airway resistance induced by histamine or bradykinin was totally inhibited by salbutamol and formoterol. The ED50 of the two mediators were 0.59 +/- 0.21 (n = 5) and 0.20 +/- 0.14 (n = 5) micrograms kg-1 respectively for salbutamol, and 0.13 +/- 0.12 (n = 6) and 0.02 +/- 0.01 (n = 6) micrograms kg-1 respectively for formoterol. 3. Salbutamol (10 and 30 micrograms kg-1) and formoterol (1 and 10 micrograms kg-1) inhibited the increase of microvascular permeability induced by histamine (30 micrograms kg-1) in the guinea-pig airways. The inhibitory effect was predominant in the trachea and the main bronchi, with a maximum inhibition of 20 to 50%. The two drugs had little or no inhibitory effect on the other structures studied, viz. nasal mucosa, larynx, proximal and distal intrapulmonary airways. 4. Salbutamol and formoterol (1 and 10 micrograms kg-1) abolished the increase in microvascular permeability induced by bradykinin (0.3 micrograms kg-1). This inhibitory effect of two beta-adrenoceptor stimulants was predominant in the trachea and the nasal mucosa where it was observed with 1 microgram kg-1 of the beta-adrenoceptor agonists.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1354535

  1. Elevated airway liquid volumes at birth: a potential cause of transient tachypnea of the newborn.

    PubMed

    McGillick, Erin Victoria; Lee, Katie; Yamaoka, Shigeo; Te Pas, Arjan B; Crossley, Kelly J; Wallace, Megan J; Kitchen, Marcus John; Lewis, Robert A; Kerr, Lauren T; DeKoninck, Philip; Dekker, Janneke; Thio, Marta; McDougall, Annie; Hooper, Stuart B

    2017-08-03

    Excessive liquid in airways and/or in distal lung tissue may underpin the respiratory morbidity associated with transient tachypnea of the newborn (TTN). However, its effects on lung aeration and respiratory function following birth are unknown. We investigated the effect of elevated airway liquid volumes on newborn respiratory function. Near term rabbit kittens (30 days gestation; term ~32 days) were delivered, had lung liquid drained and either had no liquid replaced (Control, n=7) or 30 mL/kg of liquid was re-added to the airways (liquid added; LA, n=7). Kittens were mechanically ventilated in a plethysmograph. Measures of chest and lung parameters, uniformity of lung aeration and airway size were analysed using phase contrast X-ray imaging. The maximum peak inflation pressure required to recruit a tidal volume of 8 mL/kg was significantly greater in LA compared to Control kittens (35.0±0.7 vs 26.8±0.4 cmH2O; P<0.001). LA kittens required greater time to achieve lung aeration (106±14 vs. 60±6 inflations; P=0.03) and had expanded chest walls as evidenced by an increased total chest area (32±9%; P<0.0001), lung height (17±6%; P=0.02) and curvature of the diaphragm (19±8%; P=0.04). LA kittens had lower functional residual capacity during step-wise changes in positive end expiratory pressures (PEEP; 5, 3, 0, 5 cmH20). Elevated lung liquid volumes had marked adverse effects on lung structure and function in the immediate neonatal period and reduced the ability of the lung to aerate efficiently. We speculate that elevated airway liquid volumes may underlie the initial morbidity in near term babies with TTN after birth. Copyright © 2017, Journal of Applied Physiology.

  2. Documentation of the nasal nitric oxide response to humming: methods evaluation.

    PubMed

    Shusterman, D J; Jansen, K; Weaver, E M; Koenig, J Q

    2007-09-01

    Nitric oxide (NO) is present at higher concentrations in the nasal cavity than in the lower airway, and at even higher concentrations within the paranasal sinuses proper. When the paranasal sinus ostia are patent, acoustic activity produced by vocalization with closed lips (humming) promotes mixing of sinus with nasal gases, producing a further increase in nasal NO. We wished to evaluate procedures for the documentation of the nasal NO response to humming. We compared two ATS-recommended sampling methods: 1) active exhalation of lower airway gas (parallel technique) and 2) passive aspiration of nasal gas with closed velopharynx (series technique). Variables controlled for included sampling rate, external resistance (parallel method), humming frequency, humming duration, and intertrial interval. Prior to upper airway sampling, exhaled lower airway NO was determined utilizing ATS-standardized technique. Ten volunteers (seven males and three females, aged 21-58) with no history of respiratory allergies or sino-nasal disease were studied in a single session each. The parallel technique documented an increase in nasal NO during the humming manoeuvre in all subjects (mean ratio of humming-to-quiet NO, 4.2), whereas the series technique did so in eight of 10 subjects (mean ratio 2.1). Correcting for admixture from the lower airway, the ratio of humming-to-quiet NO was greater with the parallel than series sampling technique (P < 0.05). Documentation of the response of nasal NO to humming in subjects without sino-nasal disease was consistently achievable by parallel sampling using commercially available equipment. Specific operational procedures are proposed.

  3. Inhibition of guanylyl cyclase in the airways hyperreactivity.

    PubMed

    Antosova, M; Turcan, T; Strapkova, A; Nosalova, G

    2005-01-01

    The majority of nitric oxide (NO) effects in the respiratory system are mediated via the stimulation of soluble guanylyl cyclase with subsequent generation of the second messenger--cyclic guanosine monophosphate (cGMP). We were interested in the effect of non-selective soluble guanylyl cyclase inhibitor--methylene blue on the exogenous irritant-induced bronchial hyperreactivity. Male guinea pigs were used in the experiment. The animals received non-selective soluble guanylyl cyclase inhibitor--methylene blue in a dose of 50 or 100 mg/kg b.w. 30 minutes before inhalation of the exogenous irritant--toluene vapours. The toluene exposition lasted three consecutive days during two hours in in vivo conditions. The monitoring of tracheal and lung tissue strips reactivity changes was carried out in in vitro conditions. The brochoconstrictor mediators histamine and acetylcholine in the cumulative doses (10(-8)-10(-3) mol/l) were used in the experiment. The methylene blue pretreatment induced the decrease of tracheal and lung tissue smooth muscle contraction amplitude increased by exogenous irritant--toluene. We recorded different smooth muscle response depending on the doses of inhibitor. Methylene blue in a dose of 50 mg/kg b.w. affected mainly tracheal smooth muscle, in a dose of 100 mg/kg b.w. mainly the lung tissue. The interaction between nitric oxide and soluble guanylyl cyclase can be important for bronchial reactivity changes. The changes depended on the dose of inhibitor and on the type of respiratory system tissue (trachea, lung). We can summarise that changes of the airways reactivity are not only evoked by NO/cGMP pathway but probably by any other mechanisms (Fig. 5, Ref. 26).

  4. Nitric oxide: a challenge to chiropractic

    PubMed Central

    Morgan, Lon

    2000-01-01

    The 1998 Nobel Prize in Physiology or Medicine recognized the biological significance of nitric oxide. Nitric oxide is derived from the amino acid arginine. It is intimately involved with circulatory vessel dilation where, for example, it protects against heart attacks, and is the basis for new medications such as Sildenafil (Viagra). Nitric oxide acts as a neurotransmitter and can modulate many neurological reactions. The immune system uses nitric oxide to destroy pathogens by interfering with key enzymes. Nitric oxide is responsible for both osteoclastic and osteoblastic responses in bone and is a key player in the degenerative aspects of arthritis. The process of apoptosis employs nitric oxide in the orderly removal of unneeded cells. There is clear evidence that major signaling and control mechanisms exist in the body apart from the nervous system. Chiropractic is thus faced with the challenge of how to incorporate this new knowledge which conflicts with traditional chiropractic concepts.

  5. Nitric oxide in marine photosynthetic organisms.

    PubMed

    Kumar, Amit; Castellano, Immacolata; Patti, Francesco Paolo; Palumbo, Anna; Buia, Maria Cristina

    2015-05-01

    Nitric oxide is a versatile and powerful signaling molecule in plants. However, most of our understanding stems from studies on terrestrial plants and very little is known about marine autotrophs. This review summarizes current knowledge about the source of nitric oxide synthesis in marine photosynthetic organisms and its role in various physiological processes under normal and stress conditions. The interactions of nitric oxide with other stress signals and cross talk among secondary messengers are also highlighted.

  6. NITRIC ACID RECPVERY FROM WASTE COLUTIONS

    DOEpatents

    Wilson, A.S.

    1959-04-14

    The recovery of nitric acid from aqueous nitrate solutions containing fission products as impurities is described. It is desirable to subject such solutions to concentration by evaporation since nitric acid is regenerated thereby. A difficulty, however, is that the highly radioactive fission product ruthenium is volatilized together with the nitric acid. It has been found that by adding nitrous acids ruthenium volatilization is suppressed and reduced to a negligible degree so that the distillate obtained is practically free of rutheniuim.

  7. Nitric acid recovery from waste solutions

    DOEpatents

    Wilson, A. S.

    1959-04-14

    The recovery of nitric acid from aqueous nitrate solutions containing fission products as impurities is described. It is desirable to subject such solutions to concentration by evaporation since nitric acid is regenerated thereby. A difficulty, however, is that the highly radioactive fission product ruthenium is volatilized together with the nitric acid. It has been found that by adding nitrous acid, ruthenium volatilization is suppressed and reduced to a negligible degree so that the distillate obtained is practically free of ruthenium.

  8. The Oxidation of Hydrazine by Nitric Acid

    SciTech Connect

    Karraker, D.G.

    2001-07-02

    Hydrazine nitrate-nitric acid solutions are used in the ion exchange process for separating Pu-238 and Np-237 and have been found to dissolve plutonium metal in a manner advantageous to SRP metal recovery operations. Laboratory tests on the stability of hydrazine in nitric acid solutions were performed to obtain accurate data, and the results of these tests are reported here. These tests provide sufficient information to specify temperature control for hydrazine-nitric acid solutions in plant processes.

  9. Glutathione redox regulates airway hyperresponsiveness and airway inflammation in mice.

    PubMed

    Koike, Yoko; Hisada, Takeshi; Utsugi, Mitsuyoshi; Ishizuka, Tamotsu; Shimizu, Yasuo; Ono, Akihiro; Murata, Yukie; Hamuro, Junji; Mori, Masatomo; Dobashi, Kunio

    2007-09-01

    Glutathione is the major intracellular redox buffer. We have shown that glutathione redox status, which is the balance between intracellular reduced (GSH) and oxidized (GSSG) glutathione, in antigen-presenting cells (APC) regulates the helper T cell type 1 (Th1)/Th2 balance due to the production of IL-12. Bronchial asthma is a typical Th2 disease. Th2 cells and Th2 cytokines are characteristic of asthma and trigger off an inflammation. Accordingly, we studied the effects of the intracellular glutathione redox status on airway hyperresponsiveness (AHR) and allergen-induced airway inflammation in a mouse model of asthma. We used gamma-Glutamylcysteinylethyl ester (gamma-GCE), which is a membrane-permeating GSH precursor, to elevate the intracellular GSH level and GSH/GSSG ratio of mice. In vitro, gamma-GCE pretreatment of human monocytic THP-1 cells elevated the GSH/GSSG ratio and enhanced IL-12(p70) production induced by LPS. In the mouse asthma model, intraperitoneal injection of gamma-GCE elevated the GSH/GSSG ratio of lung tissue and reduced AHR. gamma-GCE reduced levels of IL-4, IL-5, IL-10, and the chemokines eotaxin and RANTES (regulated on activation, normal T cell expressed and secreted) in bronchoalveolar lavage fluid, whereas it enhanced the production of IL-12 and IFN-gamma. Histologically, gamma-GCE suppressed eosinophils infiltration. Interestingly, we also found that gamma-GCE directly inhibited chemokine-induced eosinophil chemotaxis without affecting eotaxin receptor chemokine receptor 3 (CCR3) expressions. Taken together, these findings suggest that changing glutathione redox balance, increase in GSH level, and the GSH/GSSG ratio by gamma-GCE, ameliorate bronchial asthma by altering the Th1/Th2 imbalance through IL-12 production from APC and suppressing chemokine production and eosinophil migration itself.

  10. Airway clearance techniques for bronchiectasis.

    PubMed

    Lee, Annemarie L; Burge, Angela T; Holland, Anne E

    2015-11-23

    People with non-cystic fibrosis bronchiectasis commonly experience chronic cough and sputum production, features that may be associated with progressive decline in clinical and functional status. Airway clearance techniques (ACTs) are often prescribed to facilitate expectoration of sputum from the lungs, but the efficacy of these techniques in a stable clinical state or during an acute exacerbation of bronchiectasis is unclear. Primary: to determine effects of ACTs on rates of acute exacerbation, incidence of hospitalisation and health-related quality of life (HRQoL) in individuals with acute and stable bronchiectasis. Secondary: to determine whether:• ACTs are safe for individuals with acute and stable bronchiectasis; and• ACTs have beneficial effects on physiology and symptoms in individuals with acute and stable bronchiectasis. We searched the Cochrane Airways Group Specialised Register of trials from inception to November 2015 and PEDro in March 2015, and we handsearched relevant journals. Randomised controlled parallel and cross-over trials that compared an ACT versus no treatment, sham ACT or directed coughing in participants with bronchiectasis. We used standard methodological procedures as expected by The Cochrane Collaboration. Seven studies involving 105 participants met the inclusion criteria of this review, six of which were cross-over in design. Six studies included adults with stable bronchiectasis; the other study examined clinically stable children with bronchiectasis. Three studies provided single treatment sessions, two lasted 15 to 21 days and two were longer-term studies. Interventions varied; some control groups received a sham intervention and others were inactive. The methodological quality of these studies was variable, with most studies failing to use concealed allocation for group assignment and with absence of blinding of participants and personnel for outcome measure assessment. Heterogeneity between studies precluded inclusion of

  11. Reaction of nitric oxide with heme proteins and model compounds of hemoglobin

    SciTech Connect

    Sharma, V.S.; Traylor, T.G.; Gardiner, R.; Mizukami, H.

    1987-06-30

    Rates for the reaction of nitric oxide with several ferric heme proteins and model compounds have been measured. The NO combination rates are markedly affected by the presence or absence of distal histidine. Elephant myoglobin in which the E7 distal histidine has been replaced by glutamine reacts with NO 500-1000 times faster than do the native hemoglobins or myoglobins. By contrast, there is not difference in the CO combination rate constants of sperm whale and elephant myoglobins. Studies on ferric model compounds for the R and T states of hemoglobin indicate that their NO combination rate constants are similar to those observed for the combination of CO with the corresponding ferro derivatives. The last observation suggests that the presence of an axial water molecule at the ligand binding site of ferric hemoglobin A prevents it from exhibiting significant cooperativity in its reactions with NO.

  12. Exhaled Nitric Oxide is Decreased by Exposure to the Hyperbaric Oxygen Therapy Environment

    PubMed Central

    Puthucheary, Zudin A.; Liu, Jia; Bennett, Michael; Trytko, Barbara; Chow, Sharron; Thomas, Paul S.

    2006-01-01

    Exhaled nitric oxide (eNO) detects airway inflammation. Hyperbaric oxygen therapy (HBOT) is used for tissue hypoxia, but can cause lung damage. We measured eNO following inhalation of oxygen at different tensions and pressures. Methods. Part 1, eNO was measured before and after HBOT. Part 2, normal subjects breathed 40% oxygen. Results. Baseline eNO levels in patients prior to HBOT exposure were significantly higher than in normal subjects (P < .05). After HBOT, eNO significantly decreased in patients (15.4 ± 2.0 versus 4.4 ± 0.5 ppb, P < .001), but not in normal subjects, after either 100% O2 at increased pressure or 40% oxygen, 1 ATA. In an in vitro study, nitrate/nitrite release decreased after 90 minutes HBOT in airway epithelial (A549) cells. Conclusion. HBO exposure causes a fall in eNO. Inducible nitric oxide synthase (iNOS) may cause elevated eNO in patients secondary to inflammation, and inhibition of iNOS may be the mechanism of the reduction of eNO seen with HBOT. PMID:17392577

  13. Pulmonary expression of nitric oxide synthase isoforms in sheep with smoke inhalation and burn injury.

    PubMed

    Cox, Robert A; Jacob, Sam; Oliveras, Gloria; Murakami, Kazunori; Enkhbaatar, Perenlei; Traber, Lillian; Schmalstieg, Frank C; Herndon, David N; Traber, Daniel L; Hawkins, Hal K

    2009-03-01

    Previous studies have indicated increased plasma levels of inducible nitric oxide synthase in lung. This study further examines the pulmonary expression of nitric oxide synthase (NOS) isoforms in an ovine model of acute lung injury induced by smoke inhalation and burn injury (S+B injury). Female range bred sheep (4 per group) were sacrificed at 4, 8, 12, 24, and 48 hours after injury and immunohistochemistry was performed in tissues for various NOS isoforms. The study indicates that in uninjured sheep lung, endothelial (eNOS) is constitutively expressed in the endothelial cells associated with the airways and parenchyma, and in macrophages. Similarly, neuronal (nNOS) is constitutively present in the mucous cells of the epithelium and in neurons of airway ganglia. In uninjured lung, inducible (iNOS) was present in bronchial secretory cells and macrophages. In tissue after S+B injury, new expression of iNOS was evident in bronchial ciliated cells, basal cells, and mucus gland cells. In the parenchyma, a slight increase in iNOS immunostaining was seen in type I cells at 12 and 24 hours after injury only. Virtually no change in eNOS or nNOS was seen after injury.

  14. Protective effect of soybean oil- or fish oil-rich diets on allergic airway inflammation

    PubMed Central

    Navarro-Xavier, Roberta Araujo; de Barros, Karina Vieira; de Andrade, Iracema Senna; Palomino, Zaira; Casarini, Dulce Elena; Flor Silveira, Vera Lucia

    2016-01-01

    Background The increased prevalence of asthma and allergic diseases in westernized societies has been associated with increased intake of diets rich in n-6 fatty acids (FAs) and poor in n-3 FAs. This study aimed to analyze the prophylactic effects of treatment with a soybean oil-rich diet (rich in n-6) or fish oil (rich in n-3) in an allergic airway inflammation model on lung inflammation score, leukocyte migration, T-helper cell (Th)-2 (interleukin [IL]-4, IL-5) and Th1 (interferon [IFN]-γ, tumor necrosis factor-α) cytokines, lipoxin A4, nitric oxide, bradykinin, and corticosterone levels in bronchoalveolar lavage (BAL) or lungs. Methods Male Wistar rats fed with soybean oil- or fish oil-rich diet or standard rat chow were sensitized twice with ovalbumin–alumen and challenged twice with ovalbumin aerosol. The BAL and lungs were examined 24 hours later. Results Both diets, rich in n-6 or n-3 FAs, impaired the allergic lung inflammation and reduced leukocyte migration, eosinophil and neutrophil percentages, and IL-4/IL-5/bradykinin levels in BAL and/or lungs, as well as increased the nitric oxide levels in BAL. The soybean oil-rich diet additionally increased the levels of lipoxin A4 and corticosterone in the lungs. Conclusion Data presented demonstrated that the n-6 FA-rich diet had protective effect upon allergic airway inflammation and was as anti-inflammatory as the n-3 FA-rich diet, although through different mechanisms, suggesting that both diets could be considered as complementary therapy or a prophylactic alternative for allergic airway inflammation. PMID:27274303

  15. Airway adequacy, head posture, and craniofacial morphology.

    PubMed

    Solow, B; Siersbaek-Nielsen, S; Greve, E

    1984-09-01

    Previous studies of different samples have demonstrated associations between craniocervical angulation and craniofacial morphology, between airway obstruction by adenoids and craniofacial morphology, and between airway obstruction and craniocervical angulation. A hypothesis to account for the different sets of associations was suggested by Solow and Kreiborg in 1977. In the present study, the three sets of associations were examined in a single group of nonpathologic subjects with no history of airway obstruction. Cephalometric radiographs taken in the natural head position and rhinomanometric recordings were obtained from twenty-four children 7 to 9 years of age. Correlations were calculated between twenty-seven morphologic, eight postural, and two airway variables. A large craniocervical angle was, on the average, seen in connection with small mandibular dimensions, mandibular retrognathism, and a large mandibular inclination. Obstructed nasopharyngeal airways (defined as a small pm-ad 2 radiographic distance and a large nasal respiratory resistance, NRR, determined rhinomanometrically) were, on the average, seen in connection with a large craniocervical angle and with small mandibular dimensions, mandibular retrognathism, a large mandibular inclination, and retroclination of the upper incisors. The observed correlations were in agreement with the predicted pattern of associations between craniofacial morphology, craniocervical angulation, and airway resistance, thus suggesting the simultaneous presence of such associations in the sample of nonpathologic subjects with no history of airway obstruction.

  16. Myb permits multilineage airway epithelial cell differentiation

    PubMed Central

    Pan, Jie-hong; Adair-Kirk, Tracy L.; Patel, Anand C.; Huang, Tao; Yozamp, Nicholas S.; Xu, Jian; Reddy, E. Premkumar; Byers, Derek E.; Pierce, Richard A.; Holtzman, Michael J.; Brody, Steven L.

    2014-01-01

    The epithelium of the pulmonary airway is specially differentiated to provide defense against environmental insults, but also subject to dysregulated differentiation that results in lung disease. The current paradigm for airway epithelial differentiation is a one-step program whereby a p63+ basal epithelial progenitor cell generates a ciliated or secretory cell lineage, but the cue for this transition and whether there are intermediate steps is poorly defined. Here we identify transcription factor Myb as a key regulator that permits early multilineage differentiation of airway epithelial cells. Myb+ cells were identified as p63− and therefore distinct from basal progenitor cells, but were still negative for markers of differentiation. Myb RNAi treatment of primary-culture airway epithelial cells and Myb gene deletion in mice resulted in a p63− population with failed maturation of Foxj1+ ciliated cells, as well as Scbg1a1+ and Muc5ac+ secretory cells. Consistent with these findings, analysis of whole genome expression of Myb-deficient cells identified Myb-dependent programs for ciliated and secretory cell differentiation. Myb+ cells were rare in human airways but were increased in regions of ciliated cells and mucous cell hyperplasia in samples from subjects with chronic obstructive pulmonary disease. Together, the results show that a p63− Myb+ population of airway epithelial cells represents a distinct intermediate stage of differentiation that is required under normal conditions and may be heightened in airway disease. PMID:25103188

  17. 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.

  18. INDICATIONS FOR DISTAL RADIOULNAR ARTHROPLASTY: REPORT ON THREE CLINICAL CASES

    PubMed Central

    Santos, Cláudia; Pereira, Alexandre; Sousa, Marco; Trigeuiros, Miguel; Silva, César

    2015-01-01

    Distal radioulnar arthroplasty is an attractive solution for treating various pathological conditions of the distal radioulnar joint because it allows restoration of stability, load transmission and function. The main indications are: radioulnar impingement after partial or complete resection of the distal ulna; and degenerative, inflammatory or post-traumatic arthritis of the distal radioulnar joint. The authors present three clinical cases of distal radioulnar pathological conditions: two patients with post-traumatic sequelae and one case of distal radioulnar impingement after a Sauvé-Kapandji operation. The three cases were treated surgically with a metallic prosthesis to replace the distal ulna (First Choice - Ascension®). The first two were treated with a resurfacing prosthesis and the last one with a modular prosthesis. All of the patients had achieved pain relief and increased movement of the distal radioulnar joint after one year of postoperative follow-up. PMID:27047827

  19. 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…

  20. 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…

  1. Serelaxin Elicits Bronchodilation and Enhances β-Adrenoceptor-Mediated Airway Relaxation

    PubMed Central

    Lam, Maggie; Royce, Simon G.; Donovan, Chantal; Jelinic, Maria; Parry, Laura J.; Samuel, Chrishan S.; Bourke, Jane E.

    2016-01-01

    Treatment with β-adrenoceptor agonists does not fully overcome the symptoms associated with severe asthma. Serelaxin elicits potent uterine and vascular relaxation via its cognate receptor, RXFP1, and nitric oxide (NO) signaling, and is being clinically evaluated for the treatment of acute heart failure. However, its direct bronchodilator efficacy has yet to be explored. Tracheal rings were prepared from male Sprague-Dawley rats (250–350 g) and tricolor guinea pigs, and precision cut lung slices (PCLSs) containing intrapulmonary airways were prepared from rats only. Recombinant human serelaxin (rhRLX) alone and in combination with rosiglitazone (PPARγ agonist; recently described as a novel dilator) or β-adrenoceptor agonists (isoprenaline, salbutamol) were added either to pre-contracted airways, or before contraction with methacholine or endothelin-1. Regulation of rhRLX responses by epithelial removal, indomethacin (cyclooxygenase inhibitor), L-NAME (nitric oxide synthase inhibitor), SQ22536 (adenylate cyclase inhibitor) and ODQ (guanylate cyclase inhibitor) were also evaluated. Immunohistochemistry was used to localize RXFP1 to airway epithelium and smooth muscle. rhRLX elicited relaxation in rat trachea and PCLS, more slowly than rosiglitazone or isoprenaline, but potentiated relaxation to both these dilators. It markedly increased β-adrenoceptor agonist potency in guinea pig trachea. rhRLX, rosiglitazone, and isoprenaline pretreatment also inhibited the development of rat tracheal contraction. Bronchoprotection by rhRLX increased with longer pre-incubation time, and was partially reduced by epithelial removal, indomethacin and/or L-NAME. SQ22536 and ODQ also partially inhibited rhRLX-mediated relaxation in both intact and epithelial-denuded trachea. RXFP1 expression in the airways was at higher levels in epithelium than smooth muscle. In summary, rhRLX elicits large and small airway relaxation via epithelial-dependent and -independent mechanisms, likely

  2. Nitrite Modulates Bacterial Antibiotic Susceptibility and Biofilm Formation in Association with Airway Epithelial Cells

    PubMed Central

    Zemke, Anna C; Shiva, Sruti; Burn, Jane L.; Moskowitz, Samuel M.; Pilewski, Joseph M.; Gladwin, Mark T.; Bomberger, Jennifer M.

    2014-01-01

    Pseudomonas aeruginosa is the major pathogenic bacteria in cystic fibrosis and other forms of bronchiectasis. Growth in antibiotic resistant biofilms contributes to the virulence of this organism. Sodium nitrite has antimicrobial properties and has been tolerated as a nebulized compound at high concentrations in human subjects with pulmonary hypertension; however, its effects have not been evaluated on biotic biofilms or in combination with other clinically useful antibiotics. We grew P. aeruginosa on the apical surface of primary human airway epithelial cells to test the efficacy of sodium nitrite against biotic biofilms. Nitrite alone prevented 99% of biofilm growth. We then identified significant cooperative interactions between nitrite and polymyxins. For P. aeruginosa growing on primary CF airway cells, combining nitrite and colistimethate resulted in an additional log of bacterial inhibition compared to treating with either agent alone. Nitrite and colistimethate additively inhibited oxygen consumption by P. aeruginosa. Surprisingly, while the antimicrobial effects of nitrite in planktonic, aerated cultures are nitric oxide (NO) dependent, antimicrobial effects in other growth conditions are not. The inhibitory effect of nitrite on bacterial oxygen consumption and biofilm growth did not require NO as an intermediate as chemically scavenging NO did not block growth inhibition. These data suggest an NO-radical independent nitrosative or oxidative inhibition of respiration. The combination of nebulized sodium nitrite and colistimethate may provide a novel therapy for chronic P. aeruginosa airway infections, because sodium nitrite, unlike other antibiotic respiratory chain ‘poisons’, can be safely nebulized at high concentration in humans. PMID:25229185

  3. Nasal nitric oxide in infants before and after extubation.

    PubMed

    Chang, Chun-Cheng; Lien, Shao-Hung; Liu, Tao-Yuan; Hua, Yi-Ming; Lee, Chuen-Ming; Yuh, Yeong-Seng

    2008-11-01

    The endogenous production of nitric oxide (NO) in the upper airways is known to be high, but reports of the exact level vary, especially in newborn infants. Currently there is still no standard methodology for nasal NO measurements in neonates. In this study, we compared the levels of NO from the nasal cavity, and from the lower respiratory tracts in intubated infants together with the differences in nasal NO before and after extubation. A total of 35 intubated infants were enrolled in the study. The sampling was conducted with a fast-response chemoluminescence analyzer using the on-line tidal breathing techniques. The levels of NO in the nasal cavity were sampled using two different methods, namely nasal catheterization (Group 1), and nasal occlusion (Group 2). In both groups, the NO levels in the nasal cavity were found to be significantly higher than in the lower airway (P < 0.001). After extubation, the concentration of nasal NO in Group 1 was found to be significantly lower than before extubation (P < 0.05). There was no difference found between the levels of nasal NO in Group 2 before and after extubation (P = 0.95). Generally speaking, the concentrations of nasal NO in Group 2 were significantly higher than in Group 1 after extubation (P < 0.05). For the sample that used nasal occlusion, the nasal NO levels were more stable before and after extubation and the concentration was not affected by the breathing pattern or crying. The infants were more comfortable as well. We therefore conclude that nasal occlusion is a better method for measuring the levels of nasal NO in infants and neonates. (c) 2008 Wiley-Liss, Inc.

  4. Nasal nitric oxide: a comparison of measurement techniques.

    PubMed

    Silkoff, P E; Chatkin, J; Qian, W; Chakravorty, S; Gutierrez, C; Furlott, H; McClean, P; Rai, S; Zamel, N; Haight, J

    1999-01-01

    Nasal nitric oxide measurement may be a surrogate marker of upper airway inflammation. There is, however, no standardized measurement technique; and this led us to examine measurement techniques for acceptability and reproducibility. In five subjects we examined the flow dependence of nasal NO. In 13 healthy volunteers, nasal NO was measured on-line by five methods: 1) Tidal nasal and oral breathing: NO sampling during exclusive nasal followed by exclusive oral tidal breathing; 2) Fixed flow exhalation: NO sampling during exclusive nasal followed by exclusive oral exhalation at 100 mL/second from total lung capacity; 3) Nasal-oral aspiration: air aspirated from the mouth via both nares at 100 mL/second with glottis closure; 4) Aspiration from one nares: air aspirated from one nares at 3.3 mL/second using nitric oxide analyzer sample line with velum closure; 5) Nasal Insufflation: NO sampled at one nares as air insufflated into the other nares at a flow of 100 mL/second with velum closure. Acceptability of all methods was assessed by subjects and technicians. Nasal NO concentration showed a significant inverse correlation with transnasal flow rate. All methods showed excellent reproducibility as assessed by the intraclass correlation coefficient except tidal breathing, which showed highly variable breath-to-breath NO levels, although mean breath values were reproducible. Mean nasal NO concentrations with methods 1, 2, 3, 4, and 5 were 32.1, 50.2, 62.8, 1381, and 60.0 ppb, respectively. Velum closure was not always achieved in methods 4 and 5, whereas methods 1 and 2 required separate nasal and oral procedures. Method 5 had reduced acceptability. NO concentrations were similar with methods that used the same airflow (2, 3, and 5). Nasal NO can be sampled in different ways with excellent reproducibility. In view of the flow dependence of nasal NO, it is vital to use a constant flow rate, and lower airway NO contribution must be excluded or subtracted. The fixed flow

  5. Upper airway collapsibility in anesthetized children.

    PubMed

    Litman, Ronald S; McDonough, Joseph M; Marcus, Carole L; Schwartz, Alan R; Ward, Denham S

    2006-03-01

    We sought to establish the feasibility of measuring upper airway narrowing in spontaneously breathing, anesthetized children using dynamic application of negative airway pressure. A secondary aim was to compare differences in upper airway collapsibility after the administration of sevoflurane or halothane. Subjects were randomized to either drug for inhaled anesthetic induction. Each was adjusted to their 1 MAC value (0.9% for halothane and 2.5% for sevoflurane) and a blinded anesthesia provider held the facemask without performing manual airway opening maneuvers but with inclusion of an oral airway device. Inspiratory flows were measured during partial upper airway obstruction created by an adjustable negative pressure-generating vacuum motor inserted into the anesthesia circuit. Critical closing pressure of the pharynx (Pcrit) was obtained by plotting the peak inspiratory flow of the obstructed breaths against the corresponding negative pressure in the facemask and extrapolating to zero airflow using linear correlation. Fourteen children were enrolled, seven in each anesthetic group. Two children in the halothane group did not develop flow-limited airway obstruction despite negative pressures as low as -9 cm H2O. Pcrit for sevoflurane ranged from -6.7 to -11.6 (mean +/- sd, -9.8 +/- 1.9) cm H2O. Pcrit for halothane ranged from -8.1 to -33 (mean +/- sd, -19.4 +/- 9.3) cm H2O (sevoflurane versus halothane, P = 0.048). We conclude that when using dynamic application of negative airway pressure, halothane appears to cause less upper airway obstruction than sevoflurane at equipotent concentrations.

  6. β-Catenin–SOX2 signaling regulates the fate of developing airway epithelium

    PubMed Central

    Hashimoto, Shuichi; Chen, Huaiyong; Que, Jianwen; Brockway, Brian L.; Drake, Jeffrey A.; Snyder, Joshua C.; Randell, Scott H.; Stripp, Barry R.

    2012-01-01

    Wnt–β-catenin signaling regulates cell fate during organ development and postnatal tissue maintenance, but its contribution to specification of distinct lung epithelial lineages is still unclear. To address this question, we used a Cre recombinase (Cre)-LoxP approach to activate canonical Wnt signaling ectopically in developing lung endoderm. We found that persistent activation of canonical Wnt signaling within distal lung endoderm was permissive for normal development of alveolar epithelium, yet led to the loss of developing bronchiolar epithelium and ectasis of distal conducting airways. Activation of canonical Wnt led to ectopic expression of a lymphoid-enhancing factor and a T-cell factor (LEF and TCF, respectively) and absence of SRY (sex-determining region Y)-box 2 (SOX2) and tumor protein p63 (p63) expression in proximal derivatives. Conditional loss of SOX2 in airways phenocopied epithelial differentiation defects observed with ectopic activation of canonical Wnt. Our data suggest that Wnt negatively regulates a SOX2-dependent signaling program required for developmental progression of the bronchiolar lineage. PMID:22421361

  7. Multipotent versus differentiated cell fate selection in the developing Drosophila airways

    PubMed Central

    Matsuda, Ryo; Hosono, Chie; Samakovlis, Christos; Saigo, Kaoru

    2015-01-01

    Developmental potentials of cells are tightly controlled at multiple levels. The embryonic Drosophila airway tree is roughly subdivided into two types of cells with distinct developmental potentials: a proximally located group of multipotent adult precursor cells (P-fate) and a distally located population of more differentiated cells (D-fate). We show that the GATA-family transcription factor (TF) Grain promotes the P-fate and the POU-homeobox TF Ventral veinless (Vvl/Drifter/U-turned) stimulates the D-fate. Hedgehog and receptor tyrosine kinase (RTK) signaling cooperate with Vvl to drive the D-fate at the expense of the P-fate while negative regulators of either of these signaling pathways ensure P-fate specification. Local concentrations of Decapentaplegic/BMP, Wingless/Wnt, and Hedgehog signals differentially regulate the expression of D-factors and P-factors to transform an equipotent primordial field into a concentric pattern of radially different morphogenetic potentials, which gradually gives rise to the distal-proximal organization of distinct cell types in the mature airway. DOI: http://dx.doi.org/10.7554/eLife.09646.001 PMID:26633813

  8. Airway smooth muscle growth in asthma: proliferation, hypertrophy, and migration.

    PubMed

    Bentley, J Kelley; Hershenson, Marc B

    2008-01-01

    Increased airway smooth muscle mass is present in fatal and non-fatal asthma. However, little information is available regarding the cellular mechanism (i.e., hyperplasia vs. hypertrophy). Even less information exists regarding the functional consequences of airway smooth muscle remodeling. It would appear that increased airway smooth muscle mass would tend to increase airway narrowing and airflow obstruction. However, the precise effects of increased airway smooth muscle mass on airway narrowing are not known. This review will consider the evidence for airway smooth muscle cell proliferation and hypertrophy in asthma, potential functional effects, and biochemical mechanisms.

  9. RATE OF NITRIC OXIDE PRODUCTION BY THE LOWER AIRWAYS OF HUMAN LUNGS. (R827354C003)

    EPA Science Inventory

    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

  10. SIMULTANEOUS MEASUREMENT OF NITRIC OXIDE PRODUCTION BY CONDUCTING AND ALVEOLAR AIRWAYS OF HUMANS. (R826781)

    EPA Science Inventory

    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

  11. RATE OF NITRIC OXIDE PRODUCTION BY THE LOWER AIRWAYS OF HUMAN LUNGS. (R826781)

    EPA Science Inventory

    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

  12. Myeloid sarcoma causing airway obstruction

    PubMed Central

    Krause, John R.

    2017-01-01

    Myeloid sarcoma is an extramedullary collection of blasts of the myeloid series that partially or totally effaces the architecture of the tissue in which it is found. These tumors have been described in many sites of the body, but the skin, lymph nodes, gastrointestinal tract, bone, soft tissue, and testes are most common. They can arise in a patient following the diagnosis of acute myeloid leukemia, but they may also be precursors of leukemia and should be considered diagnostic for acute myeloid leukemia. The differential diagnosis of this neoplasm includes malignant lymphoma, with which it is often mistaken, leading to diagnostic and therapeutic delays. We present the case of an 84-year-old African American man with a history of renal disease secondary to hypertension and coronary artery disease without any prior history of malignancies who presented with airway obstruction. He was diagnosed with a myeloid sarcoma of the mediastinum compressing his trachea. PMID:28405080

  13. HEREDITARY DISTAL FORELEG CURVATURE IN THE RABBIT

    PubMed Central

    Pearce, Louise

    1960-01-01

    An inwardly directed curvature of the distal segment of both forelegs of the rabbit has been described. The condition was detected at 2 to 3 weeks of age, developed rapidly, and reached its final and permanent stage at 2 to 3 months of age. Only the distal epiphysis of the ulna was primarily affected and this in the form of a massive chondrodystrophic lesion accompanied by a progressive curvature of the shaft. The curvature of the growing radius was a secondary effect due to the firm, immovable, anatomical connection of the ulna and radius. The positional changes of the wrist and paw were likewise effects secondary to the changed form of the ulna and radius. The bowing abnormality occurred only in certain families of pure bred Beveren, Belgian, French Silver, and Dutch rabbits and was found to be inherited. The mode of inheritance was on the basis of a single recessive unit factor (5). PMID:13733755

  14. Regional deposition of particles in an image-based airway model: large-eddy simulation and left-right lung ventilation asymmetry.

    PubMed

    Lambert, Andrew R; O'Shaughnessy, Patrick; Tawhai, Merryn H; Hoffman, Eric A; Lin, Ching-Long

    2011-01-01

    Regional deposition and ventilation of particles by generation, lobe and lung during steady inhalation in a computed tomography (CT) based human airway model are investigated numerically. The airway model consists of a seven-generation human airway tree, with oral cavity, pharynx and larynx. The turbulent flow in the upper respiratory tract is simulated by large-eddy simulation. The flow boundary conditions at the peripheral airways are derived from CT images at two lung volumes to produce physiologically-realistic regional ventilation. Particles with diameter equal to or greater than 2.5 microns are selected for study because smaller particles tend to penetrate to the more distal parts of the lung. The current generational particle deposition efficiencies agree well with existing measurement data. Generational deposition efficiencies exhibit similar dependence on particle Stokes number regardless of generation, whereas deposition and ventilation efficiencies vary by lobe and lung, depending on airway morphology and airflow ventilation. In particular, regardless of particle size, the left lung receives a greater proportion of the particle bolus as compared to the right lung in spite of greater flow ventilation to the right lung. This observation is supported by the left-right lung asymmetry of particle ventilation observed in medical imaging. It is found that the particle-laden turbulent laryngeal jet flow, coupled with the unique geometrical features of the airway, causes a disproportionate amount of particles to enter the left lung.

  15. Study of Atmospheric Nitric Oxide

    NASA Technical Reports Server (NTRS)

    Dalgarno, A.

    1998-01-01

    We investigated the contribution of energetic nitrogen atoms to the production of nitric oxide in the thermosphere and their influence on the infrared emission spectrum. The nitric oxide molecules are important contributors to the cooling of the atmosphere. We first pointed out that in determining the energy distribution of the nitrogen atoms, it is important to take into account the thermal motion of the atmospheric gases. It had been ignored in all earlier studies. The source spectra are broadened considerably by the center of mass motion of the reactants. We worked out the consequences for the production of nitric oxide at night, using as sources of energetic N atoms, NO(+) + e yield N + O, N(D-2) + O yield N + O. The high energy tail is enhanced by orders of magnitude. We had earlier suggested (Sharma et al. 1993) that the reaction of energetic nitrogen atoms with O2 was responsible for the rotationally enhanced NO identified in the infrared spectrum. Our calculations provided quantitative confirmation of the suggestion. We proceeded to explore the validity of another approximation used in earlier analyses, the hard sphere approximation for the energy loss in elastic collisions. We carried out precise quantum mechanical calculations of the elastic 2 differential scattering of nitrogen atoms in collisions with oxygen atoms and showed that although the hard sphere approximation was nowhere of high precision, reasonable results could be obtained with an effective cross section of 6 x 10(exp 15)sq cm. We also initiated a program to include inelastic energy loss processes in the determination of the energy distribution function. We began a calculation of the rotation and vibrational excitation cross sections of molecular nitrogen and nitrogen atoms and developed a method for including inelastic energy loss as a function of scattering angle in the Boltzmann equation. A procedure for obtaining the solution of the Boltzman equation was worked out.

  16. Pharmacology of airway afferent nerve activity

    PubMed Central

    Undem, Bradley J; Carr, Michael J

    2001-01-01

    Afferent nerves in the airways serve to regulate breathing pattern, cough, and airway autonomic neural tone. Pharmacologic agents that influence afferent nerve activity can be subclassified into compounds that modulate activity by indirect means (e.g. bronchial smooth muscle spasmogens) and those that act directly on the nerves. Directly acting agents affect afferent nerve activity by interacting with various ion channels and receptors within the membrane of the afferent terminals. Whether by direct or indirect means, most compounds that enter the airspace will modify afferent nerve activity, and through this action alter airway physiology. PMID:11686889

  17. 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. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Firefighting acutely increases airway responsiveness.

    PubMed

    Sherman, C B; Barnhart, S; Miller, M F; Segal, M R; Aitken, M; Schoene, R; Daniell, W; Rosenstock, L

    1989-07-01

    The acute effects of the products of combustion and pyrolysis on airway responsiveness among firefighters are poorly documented. To study this relationship, spirometry and methacholine challenge testing (MCT) were performed on 18 active Seattle firefighters before and 5 to 24 h after firefighting. Body plethysmography was used to measure changes in specific airway conductance (SGaw), and results of MCT were analyzed using PD35-SGaw, the cumulative dose causing a 35% decrease in SGaw. Subjects who did not react by the end of the protocol were assigned a value of 640 inhalational units, the largest cumulative dose. Fire exposure was defined as the total time (hours) spent without a self-contained breathing apparatus at the firesite and was categorized as mild (less than 1 h, n = 7), moderate (1 to 2 h, n = 5), or severe (greater than 2 h, n = 6). Mean age of the 18 firefighters was 36.7 +/- 6.7 yr (range, 25 to 51), with a mean of 9.1 +/- 7.9 active years in the trade (range, zero to 22). None was known to be asthmatic. After firefighting, FEV1 % predicted (%pred) and FEF25-75 %pred significantly decreased by means of 3.4 +/- 1.1% and 5.6 +/- 2.6%, respectively. The mean decline in PD35-SGaw after firefighting was 184.5 +/- 53.2 units (p = 0.003). This observed decline in PD35-SGaw could not be explained by decrements in prechallenge SGaw, FEV1, or FVC.(ABSTRACT TRUNCATED AT 250 WORDS)

  19. The Development and Application of Airway Devices in China

    PubMed Central

    Chen, Xiangdong; Ma, Wuhua; Liu, Renyu; Yao, Shanglong

    2017-01-01

    Airway management is one of the most important tasks for anesthesiologists. Anesthesiologists are experts in airway management and have made tremendous contribution to the development of the airway devices. Chinese anesthesiologists have made significant contribution in introducing advanced airway management and developing innovative techniques and devices for airway management in China. This article overviews the development and application of airway devices in China as well as the dedication and contribution of Chinese experts in the development of novel airway devices. With the development of science and technology accompanied by the advanced knowledge in airway management, more effective and safe artificial airways will be developed for clinical practice. The authors believe that Chinese experts will continue their outstanding contribution to the development of innovative airway devices, systems and knowledge. PMID:28191485

  20. Assessment of Vibratory Characteristics in Children Following Airway Reconstruction Using Flexible and Rigid Endoscopy and Stroboscopy.

    PubMed

    Zacharias, Stephanie R C; Weinrich, Barbara; Brehm, Susan Baker; Kelchner, Lisa; Deliyski, Dimitar; Tabangin, Meredith; de Alarcon, Alessandro

    2015-10-01

    Up to half of children have substantial dysphonia after airway reconstruction. Visual assessment of vocal function is valuable. Feasibility of flexible and rigid endoscopy has been reported; however, the clinical utility of stroboscopy has not been examined. Rating of vibratory characteristics, such as mucosal wave and amplitude of vibration, is essential for the development of interventions to improve voice outcomes. To examine (1) clinicians’ ratings of anatomical and physiological features in children following airway reconstruction on initial voice evaluation using videolaryngostroboscopy and (2) the relationship of age to the type of endoscopy used. Retrospective medical record review of 32 patients aged 3 to 21 years evaluated for post–airway reconstruction dysphonia between July 2011 and July 2012 at a quaternary care children’s hospital. Clinical voice evaluation protocol including rigid and/or flexible endoscopy with stroboscopy. Demographic and voice quality characteristics were collected. The ability to complete endoscopy and ratings of anatomical and/or physiological features were assessed by a consensus of 4 clinicians. A t test was used to determine whether age was a significant factor in successful completion of videolaryngostroboscopy. Of 31 children who underwent flexible videolaryngostroboscopy, 22 (71%) examinations were completed with a distal chip endoscope and 9 (29%) with a fiberoptic. Significant differences were found in age between children who completed the distal chip vs. fiberoptic examination (mean [SD], 7.3 [2.7] vs. 5.5 [6.2] years; P = .05). Rigid endoscopy was attempted for 14 (44%) of 32 patients; 9 examinations (64%) were successful. Significant differences were found in age between patients for whom a rigid endoscopy could be successfully completed vs. those for whom it was not (mean [SD], 12.9 [3.4] vs. 6.2 [2.1] years; P < .001). Eighteen (56%) were glottic phonators, 8 (25%) supraglottic, and 6 (19%) aphonic. Vibratory

  1. Distal biceps tendon injuries: diagnosis and management.

    PubMed

    Ramsey, M L

    1999-01-01

    Rupture of the distal biceps tendon occurs most commonly in the dominant extremity of men between 40 and 60 years of age when an unexpected extension force is applied to the flexed arm. Although previously thought to be an uncommon injury, distal biceps tendon ruptures are being reported with increasing frequency. The rupture typically occurs at the tendon insertion into the radial tuberosity in an area of preexisting tendon degeneration. The diagnosis is made on the basis of a history of a painful, tearing sensation in the antecubital region. Physical examination demonstrates a palpable and visible deformity of the distal biceps muscle belly with weakness in flexion and supination. The ability to palpate the tendon in the antecubital fossa may indicate partial tearing of the biceps tendon. Plain radiographs may show hypertrophic bone formation at the radial tuberosity. Magnetic resonance imaging is generally not required to diagnose a complete rupture but may be useful in the case of a partial rupture. Early surgical reattachment to the radial tuberosity is recommended for optimal results. A modified two-incision technique is the most widely used method of repair, but anterior single-incision techniques may be equally effective provided the radial nerve is protected. The patient with a chronic rupture may benefit from surgical reattachment, but proximal retraction and scarring of the muscle belly can make tendon mobilization difficult, and inadequate length of the distal biceps tendon may necessitate tendon augmentation. Postoperative rehabilitation must emphasize protected return of motion for the first 8 weeks after repair. Formal strengthening may begin as early as 8 weeks, with a return to unrestricted activities, including lifting, by 5 months.

  2. Fractures of Distal Radius: An Overview

    PubMed Central

    Meena, Sanjay; Sharma, Pankaj; Sambharia, Abhishek Kumar; Dawar, Ashok

    2014-01-01

    Fractures of distal radius account for up to 20% of all fractures treated in emergency department. Initial assessment includes a history of mechanism of injury, associated injury and appropriate radiological evaluation. Treatment options include conservative management, internal fixation with pins, bridging and non-bridging external fixation, dorsal or volar plating with/without arthroscopy assistance. However, many questions regarding these fractures remain unanswered and good prospective randomized trials are needed. PMID:25657938

  3. [Laparoscopic distal resection of the pancreas].

    PubMed

    Gürlich, R; Sixta, B; Oliverius, M; Kment, M; Rusina, R; Spicák, J; Sváb, J

    2005-09-01

    During the last two years, reports on laparoscopic procedures of the pancreas have been on increase. Laparoscopic resection of the pancreatic cauda is indicated, primarily, for benign cystic lesions of the cauda of the pancreas and for neuroendocrine tumors of the pancreas (mainly insulinomas). We have not recorded any report on the above procedure in the Czech literature. Therefore, in our case review, we have described laparoscopic distal resection of the pancreas with splenectomy for a pseudopapillary tumor of the pancreas.

  4. Diagnostic and Therapeutic Advances: Distal Symmetric Polyneuropathy

    PubMed Central

    Callaghan, Brian C.; Price, Raymond S.; Feldman, Eva L.

    2016-01-01

    Importance Peripheral neuropathy is a highly prevalent and morbid condition affecting 2–7% of the population. Patients frequently suffer from pain and are at risk of falls, ulcerations, and amputations. We aimed to review recent diagnostic and therapeutic advances in peripheral neuropathy in distal symmetric polyneuropathy, the most common subtype of peripheral neuropathy. Observations and Advances Current evidence supports limited routine laboratory testing in patients with distal symmetric polyneuropathy. Patients without a known cause should have a complete blood count, comprehensive metabolic panel, B12, serum protein electrophoresis with immunofixation, fasting glucose, and a glucose tolerance test. The presence of atypical features such as asymmetry, non-length-dependence, motor predominance, acute or subacute onset, and/or prominent autonomic involvement should prompt a consultation with a neurologist or neuromuscular specialist. Electrodiagnostic tests and magnetic resonance imaging of the neuroaxis are the main drivers of the cost of the diagnostic evaluation, but evidence supporting their use is lacking. Strong evidence supports the use of tricyclic antidepressants, serotonin and norepinephrine reuptake inhibitors, and voltage-gated calcium channel ligands in the treatment of neuropathic pain. More intensive glucose control substantially reduces the incidence of distal symmetric polyneuropathy in patients with type 1 diabetes, but does not in type 2 diabetes. Conclusions and Relevance The opportunity exists to improve guideline concordant testing in distal symmetric polyneuropathy patients. Moreover, the role of electrodiagnostic tests needs to be further defined, and interventions to reduce magnetic resonance imaging use in this population are needed. Even though several efficacious medications exist for neuropathic pain treatment, pain is still under-recognized and undertreated. New disease modifying medications are needed to prevent and treat

  5. Distal renal tubular acidosis with hereditary spherocytosis.

    PubMed

    Sinha, Rajiv; Agarwal, Indira; Bawazir, Waleed M; Bruce, Lesley J

    2013-07-01

    Hereditary spherocytosis (HS) and distal renal tubular acidosis (dRTA), although distinct entities, share the same protein i.e. the anion exchanger1 (AE1) protein. Despite this, their coexistence has been rarely reported. We hereby describe the largest family to date with co-existence of dRTA and HS and discuss the molecular basis for the co-inheritance of these conditions.

  6. Airway clearance techniques for bronchiectasis.

    PubMed

    Lee, Annemarie L; Burge, Angela; Holland, Anne E

    2013-05-31

    People with non-cystic fibrosis bronchiectasis commonly experience chronic cough and sputum production and these features may be associated with progressive decline in clinical status. Airway clearance techniques (ACTs) are often prescribed to facilitate expectoration of sputum from the lungs, but the efficacy of these techniques in a stable clinical state or during an acute exacerbation of bronchiectasis is unclear. Primary: to determine the effects of ACTs on the rate of acute exacerbations, incidence of hospitalisation and health-related quality of life in individuals with acute and stable bronchiectasis.Secondary: to determine whether a) ACTs are safe for individuals with acute and stable bronchiectasis and b) ACTs have beneficial effects on physiology and symptoms in individuals with acute and stable bronchiectasis. We searched the Cochrane Airways Group Specialised Register of trials from inception to October 2012, PEDro in October 2012 and handsearched relevant journals. Randomised controlled parallel and cross-over trials that compared an ACT to no treatment, sham ACT or directed coughing in participants with bronchiectasis. We used standard methodological procedures expected by The Cochrane Collaboration. Five studies involving 51 participants met the inclusion criteria of the review, all of which were cross-over design. Four studies were on adults with stable bronchiectasis, and the other study was on clinically stable children with bronchiectasis. Three studies were single treatment sessions, two were longer-term studies. The interventions varied and some control groups received a sham intervention while others were inactive. The methodological quality of the studies was variable and the studies were not able to blind participants and personal. Heterogeneity between studies precluded these data from meta-analysis and the review was therefore narrative.One study on 20 adults comparing an airway oscillatory device with no treatment found no significant

  7. Hyperpolarized 3He magnetic resonance imaging ventilation defects in asthma: relationship to airway mechanics.

    PubMed

    Leary, Del; Svenningsen, Sarah; Guo, Fumin; Bhatawadekar, Swati; Parraga, Grace; Maksym, Geoffrey N

    2016-04-01

    In patients with asthma, magnetic resonance imaging (MRI) provides direct measurements of regional ventilation heterogeneity, the etiology of which is not well-understood, nor is the relationship of ventilation abnormalities with lung mechanics. In addition, respiratory resistance and reactance are often abnormal in asthmatics and the frequency dependence of respiratory resistance is thought to reflect ventilation heterogeneity. We acquiredMRIventilation defect maps, forced expiratory volume in one-second (FEV1), and airways resistance (Raw) measurements, and used a computational airway model to explore the relationship of ventilation defect percent (VDP) with simulated measurements of respiratory system resistance (Rrs) and reactance (Xrs).MRIventilation defect maps were experimentally acquired in 25 asthmatics before, during, and after methacholine challenge and these were nonrigidly coregistered to the airway tree model. Using the model coregistered to ventilation defect maps, we narrowed proximal (9th) and distal (14th) generation airways that were spatially related to theMRIventilation defects. The relationships forVDPwith Raw measured using plethysmography (r = 0.79), and model predictions of Rrs>14(r = 0.91,P < 0.0001) and Rrs>9(r = 0.88,P < 0.0001) were significantly stronger (P = 0.005;P = 0.03, respectively) than withFEV1(r = -0.68,P = 0.0001). The slopes for the relationship ofVDPwith simulated lung mechanics measurements were different (P < 0.0001); among these, the slope for theVDP-Xrs0.2relationship was largest, suggesting thatVDPwas dominated by peripheral airway heterogeneity in these patients. In conclusion, as a first step toward understanding potential links between lung mechanics and ventilation defects, impedance predictions were made using a computational airway tree model with simulated constriction of airways related to ventilation defects measured in mild-moderate asthmatics. © 2016 The Authors. Physiological Reports

  8. Novel effects of nitric oxide

    NASA Technical Reports Server (NTRS)

    Davis, K. L.; Martin, E.; Turko, I. V.; Murad, F.

    2001-01-01

    Nitric oxide (NO), a simple free radical gas, elicits a surprisingly wide range of physiological and pathophysiological effects. NO interacts with soluble guanylate cyclase to evoke many of these effects. However, NO can also interact with molecular oxygen and superoxide radicals to produce reactive nitrogen species that can modify a number of macromolecules including proteins, lipids, and nucleic acids. NO can also interact directly with transition metals. Here, we have reviewed the non--3',5'-cyclic-guanosine-monophosphate-mediated effects of NO including modifications of proteins, lipids, and nucleic acids.

  9. Hexanitrostilbene Recrystallized from Nitric Acid

    DTIC Science & Technology

    1979-09-19

    process. The author wishes to acknowledge Mr. Daniel Polansky for the X-Ray/N-Ray, Ms. Eleonore Kayser for the chemical analyses and nitric acid...recrystallized HNS-II using a pH meter and a solvent mixture consisting of 90% H2 0 and 10% DMSO by volume. The method was developed by Eleonore Kayser...65-142, 26 Aug 1965. 4. Syrop, Leroy J., "Process for Recrystallizing Hexanitrostilbene," U. S. Patent 3,699,176, 17 Oct 1972. 5. Kayser, Eleonore G

  10. [Nitric oxide in dengue pathology].

    PubMed

    Rodriguez-Ortega, M

    1998-01-01

    Nitric oxide (NO) is a multifunctional molecule that is involved in citotoxic as well as citoprotective processes, it's synthesis is highly regulated by the cell because an alteration in NO production is associated with a variety of pathologies, such as Septic, Anaphylactic and Hemorrhagic Shock. The clinical feature of dengue virus infection has a spectrum that goes from mild, dengue fever, to a severe disease, dengue hemorrhagic fever/dengue shock. Here, some evidences are discussed that links NO with the pathology of the severe disease cause by dengue virus.

  11. 75 FR 56052 - Action Affecting Export Privileges; Mahan Airways and Gatewick LLC

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-15

    ... TDO both Blue Airways FZE, of Dubai, United Arab Emirates (``the UAE''), and Blue Airways, also of Dubai, United Arab Emirates (``Blue Airways UAE''), as persons related to Blue Airways of Armenia. (Blue Airways of Armenia, Blue Airways FZE, and Blue Airways UAE are hereinafter collectively referred to as the...

  12. 76 FR 12318 - Action Affecting Export Privileges; Mahan Airways, Gatewick LLC; Pejman Mahmood Kosarayanifard...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-07

    ..., of Dubai, United Arab Emirates (``the UAE''), and Blue Airways, also of Dubai, United Arab Emirates (``Blue Airways UAE''), as persons related to Blue Airways of Armenia. (Blue Airways of Armenia, Blue Airways FZE, and Blue Airways UAE are hereinafter collectively referred to as the ``Blue Airways...

  13. Evolution of the distal radioulnar joint.

    PubMed

    Almquist, E E

    1992-02-01

    The evolution of the wrist joint began 400 million years ago with the pectoral fins in primitive fish. The five-rayed extremity with 13 carpal bones and a syndesmotic distal radioulnar joint first appeared in the primitive amphibian, Eryops, some 230 million years ago. These characteristics remained similar through the evolution of the amphibians and of mammals and were retained when primates evolved to hominids. As later-developing, larger-sized hominids began competing for food, brachiation (the ability to swing from tree branch to tree branch) became more important, and a synovial distal radioulnar joint evolved, allowing pronation/supination of the wrist. The development of bipedalism freed the upper extremity from the requirements of locomotion, placing greater emphasis on increasing wrist mobility. The ability to supinate and pronate was an immense advantage to hominids in caring for their young, defending themselves, and gathering food. It was also critical in efficient tool handling, which developed two million years ago. The mobility of the distal radioulnar joint, along with the prehensile thumb and increasing brain function, are hallmarks of the late-evolving hominids.

  14. Novel topical therapies for distal colitis.

    PubMed

    Lawrance, Ian Craig

    2010-10-06

    Distal colitis (DC) can be effectively treated with topical 5ASA agents. Suppositories target the rectum while enemas can reliably reach the splenic flexure. Used in combination with oral 5ASAs, the control of the inflammation is even more effective. Unfortunately, resistant DC does occur and can be extremely challenging to manage. In these patients, the use of steroids, immunosuppressants and the anti-tumor necrosis factor α agents are often required. These, however, can be associated with systemic side effects and are not always effective. The investigation of new topical therapeutic agents is thus required as they are rarely associated with significant blood drug levels and side effects are infrequent. Some of the agents that have been proposed for use in resistant distal colitis include butyrate, cyclosporine and nicotine enemas as well as tacrolimus suppositories and tacrolimus, ecabet sodium, arsenic, lidocaine, rebamipide and Ridogrel(®) enemas. Some of these agents have demonstrated impressive results but the majority of the agents have only been assessed in small open-labelled patient cohorts. Further work is thus required with the investigation of promising agents in the context of randomized double-blinded placebo controlled trials. This review aims to highlight those potentially effective therapies in the management of resistant distal colitis and to promote interest in furthering their investigation.

  15. Distal Embolic Protection for Renal Arterial Interventions

    SciTech Connect

    Dubel, Gregory J. Murphy, Timothy P.

    2008-01-15

    Distal or embolic protection has intuitive appeal for its potential to prevent embolization of materials generated during interventional procedures. Distal protection devices (DPDs) have been most widely used in the coronary and carotid vascular beds, where they have demonstrated the ability to trap embolic materials and, in some cases, to reduce complications. Given the frequency of chronic kidney disease in patients with renal artery stenosis undergoing stent placement, it is reasonable to propose that these devices may play an important role in limiting distal embolization in the renal vasculature. Careful review of the literature reveals that atheroembolization does occur during renal arterial interventions, although it often goes undetected. Early experience with DPDs in the renal arteries in patients with suitable anatomy suggests retrieval of embolic materials in approximately 71% of cases and renal functional improvement/stabilization in 98% of cases. The combination of platelet inhibition and a DPD may provide even greater benefit. Given the critical importance of renal functional preservation, it follows that everything that can be done to prevent atheroembolism should be undertaken including the use of DPDs when anatomically feasible. The data available at this time support a beneficial role for these devices.

  16. Unreamed intramedullary nailing in distal tibial fractures.

    PubMed

    Salem, Khaled Hamed

    2013-10-01

    Unreamed nailing has gained acceptance in the treatment of diaphyseal long bone fractures, especially in cases with polytrauma or high-energy injuries. Its application in distal tibial fractures, however, remains controversial. In this study, 101 distal tibial fractures treated using closed unreamed nailing were reviewed after a mean follow-up of 32 months. There were 59 type A und 42 type B fractures. The most common fracture pattern was the A1 spiral fracture (n = 40) followed by the B2 wedge fracture (n = 18). Intra-articular extension was encountered in 14 cases. One-fourth of the patients (n = 24) had open injuries. Forty-seven patients had additional injuries, and nearly one-third of them were polytraumatised. Union occurred after a mean time of 23.9 (range, 11-134) weeks. There were 13 cases of delayed union and seven non-unions; all healed eventually with additional surgery in only six fractures. Malunion was seen in 12 cases (five valgus, two varus and five external torsion), ten of which were associated with unplated fibular fractures. Three fractures (two open) were treated for deep infection. The most common complication seen was fatigue failure of the locking screws (27 cases). Unreamed nailing of distal tibial fractures is associated with a rather high rate of bone healing complications and locking screw failure. The decision for its use in the notoriously challenging fractures of this segment should be critically considered.

  17. Distal arthrogryposis: clinical and genetic findings.

    PubMed

    Kimber, Eva; Tajsharghi, Homa; Kroksmark, Anna-Karin; Oldfors, Anders; Tulinius, Már

    2012-08-01

    Distal arthrogryposis is characterized by congenital contractures predominantly in hands and feet. Mutations in sarcomeric protein genes are involved in several types of distal arthrogryposis. Our aim is to describe clinical and molecular genetic findings in individuals with distal arthrogryposis and evaluate the genotype-phenotype correlation. We investigated 39 patients from 21 families. Clinical history, including neonatal findings, joint involvement and motor function, was documented. Clinical examination was performed including evaluation of muscle strength. Molecular genetic investigations were carried out in 19 index cases. Muscle biopsies from 17 patients were analysed. A pathogenic mutation was found in six families with 19 affected family members with autosomal dominant inheritance and in one child with sporadic occurrence. In three families and in one child with sporadic form, the identified mutation was de novo. Muscle weakness was found in 17 patients. Ambulation was affected in four patients and hand function in 28. Fourteen patients reported pain related to muscle and joint affection. The clinical findings were highly variable between families and also within families. Mutations in the same gene were found in different syndromes suggesting varying clinical penetrance and expression, and different gene mutations were found in the same clinical syndrome demonstrating genetic heterogeneity. © 2012 The Author(s)/Acta Paediatrica © 2012 Foundation Acta Paediatrica.

  18. Triplane fracture of the distal radius.

    PubMed

    García-Mata, Serafín; Hidalgo-Ovejero, Angel

    2006-07-01

    A case of triplane fracture of the distal radius is reported in a 13-year-old boy. This exceptional fracture showed displacement, and was healed by closed reduction and 6 weeks of external immobilization. Eighteen months later, the patient showed complete physeal arrest of the distal radius, with radio-ulnar length discrepancy but without any repercussion on wrist mobility. The patient was declared asymptomatic 3 years after the injury. Prompt, physiological physeal arrest reduces the potential of growth deformity. These fractures must be treated conservatively by closed reduction (if displacement exists) and external immobilization, just like a normal one-plane fracture. We may suppose that final radio-ulnar discrepancy could lead to a painful and symptomatic ulno-carpal conflict in adult life. The following characteristics can be associated with this rare fracture: (1) occurrence close to the end of the growth period, as in other types of triplane fractures; (2) evolution towards partial or complete growth arrest of the physis, not requiring treatment and (3) stability of the fracture after closed reduction. In the present case, as in the other reported cases, it may also be added that orthopaedic treatment has been the rule, in contrast with triplane fractures occurring in the distal tibia, in which surgical treatment is indicated.

  19. Distal symmetrical polyneuropathy: definition for clinical research.

    PubMed

    England, J D; Gronseth, G S; Franklin, G; Miller, R G; Asbury, A K; Carter, G T; Cohen, J A; Fisher, M A; Howard, J F; Kinsella, L J; Latov, N; Lewis, R A; Low, P A; Sumner, A J

    2005-01-01

    The objective of this report was to develop a case definition of "distal symmetrical polyneuropathy" to standardize and facilitate clinical research and epidemiological studies. A formalized consensus process was employed to reach agreement after a systematic review and classification of evidence from the literature. The literature indicates that symptoms alone have relatively poor diagnostic accuracy in predicting the presence of polyneuropathy; signs are better predictors of polyneuropathy than symptoms; and single abnormalities on examination are less sensitive than multiple abnormalities in predicting the presence of polyneuropathy. The combination of neuropathic symptoms, signs, and electrodiagnostic findings provides the most accurate diagnosis of distal symmetrical polyneuropathy. A set of case definitions was rank ordered by likelihood of disease. The highest likelihood of polyneuropathy (useful for clinical trials) occurs with a combination of multiple symptoms, multiple signs, and abnormal electrodiagnostic studies. A modest likelihood of polyneuropathy (useful for field or epidemiological studies) occurs with a combination of multiple symptoms and multiple signs when the results of electrodiagnostic studies are not available. A lower likelihood of polyneuropathy occurs when electrodiagnostic studies and signs are discordant. For research purposes, the best approach for defining distal symmetrical polyneuropathy is a set of case definitions rank ordered by estimated likelihood of disease. The inclusion of this formalized case definition in clinical and epidemiological research studies will ensure greater consistency of case selection.

  20. Distal tendinosis of the tibialis anterior tendon.

    PubMed

    Beischer, Andrew D; Beamond, Ben M; Jowett, Andrew J L; O'Sullivan, Richard

    2009-11-01

    Disorders of the tibialis anterior (TA) tendon have infrequently been reported but spontaneous rupture of this tendon is well recognized. The clinical presentation of tendinosis without rupture of the distal TA has not previously been reported and is the basis of this paper. A study of 29 patients diagnosed with distal TA tendinosis was undertaken. Data collected included, patient demographics, weight, height, pain profile and examination findings. All patients underwent MRI of the symptomatic foot. Operative findings of those patients undergoing surgery for this condition were collected. Twenty-nine patients (32 feet) were included in the study group. Their mean age was 62 years and 27 patients were female. Twenty-one patients were overweight. The usual presenting symptom was burning medial midfoot pain that was often reported to be worst at night. Swelling over the TA tendon was frequently observed. On MRI the TA was thickened in all patients. Longitudinal split tears were observed in 19 feet. Chondral thinning and/or osteophyte formation at the first tarsometatarsal or medial naviculocuneiform joints was observed in 11 feet. Eleven feet underwent surgery. Universally the TA tendon was macroscopically thickened and had lost its normal fibrillary appearance. Longitudinal split tears were observed in eight tendons. Pathology was typical of a degenerative tendinosis. Distal TA tendinosis is a condition that seems to predominantly affect overweight elderly women. It often presents with nocturnal burning medial midfoot pain.

  1. Arthrogryposis multiplex congenita: airway concerns in an emergency situation.

    PubMed

    Gupta, Babita; Suri, Saurabh; Kohli, Santvana; Ahmad, Suma; Gupta, Surender

    2014-06-01

    Difficult airway is always of special concern to anesthesiologists, but in a trauma setting where having a secured airway is most important, the incidence of difficult airway increases manifold. We report a "cannot ventilate cannot intubate" situation in a trauma patient who was later diagnosed to have arthrogryposis multiplex congenita, a syndrome known to affect the airway, and in whom all measures of securing a nonsurgical airway failed. Copyright © 2014. Published by Elsevier B.V.

  2. Does chronic physical activity level modify the airway inflammatory response to an acute bout of exercise in the postprandial period?

    PubMed

    Kurti, Stephanie P; Rosenkranz, Sara K; Chapes, Stephen K; Teeman, Colby S; Cull, Brooke J; Emerson, Sam R; Levitt, Morton H; Smith, Joshua R; Harms, Craig A

    2017-02-01

    Recent studies have confirmed that a single high-fat meal (HFM) leads to increased airway inflammation. However, exercise is a natural anti-inflammatory and may modify postprandial airway inflammation. The postprandial airway inflammatory response is likely to be modified by chronic physical activity (PA) level. This study investigated whether chronic PA modifies the airway inflammatory response to an acute bout of exercise in the postprandial period in both insufficiently active and active subjects. Thirty-nine nonasthmatic subjects (20 active, 13 males/7 females) who exceeded PA guidelines (≥150 min moderate-vigorous PA/week) and 19 insufficiently active (6 males/13 females) underwent an incremental treadmill test to exhaustion to determine peak oxygen uptake. Subjects were then randomized to a condition (COND), either remaining sedentary (CON) or exercising (EX) post-HFM. Exercise was performed at the heart rate corresponding to 60% peak oxygen uptake on a treadmill for 1 h post-HFM (63% fat, 10 kcal/kg body weight). Blood lipids and exhaled nitric oxide (eNO: marker of airway inflammation) were measured at baseline and 2 h and 4 h post-HFM. Sputum differential cell counts were performed at baseline and 4 h post-HFM. The mean eNO response for all groups increased at 2 h post-HFM (∼6%) and returned to baseline by 4 h (p = 0.03). There was a time × COND interaction (p = 0.04), where EX had a greater eNO response at 4 h compared with CON. Sputum neutrophils increased at 4 h post-HFM (p < 0.05). These findings suggest that airway inflammation occurs after an HFM when exercise is performed in the postprandial period, regardless of habitual activity level.

  3. Determinants of exhaled nitric oxide levels in healthy, nonsmoking African American adults.

    PubMed

    Levesque, Marc C; Hauswirth, David W; Mervin-Blake, Sabrena; Fernandez, Carolyn A; Patch, Kistie B; Alexander, Katie M; Allgood, Sallie; McNair, Patrice D; Allen, Andrew S; Sundy, John S

    2008-02-01

    Asthma is a significant cause of morbidity and mortality for African Americans. Fraction of exhaled nitric oxide (FeNO) levels are increased in patients with asthma, and airway levels of nitric oxide metabolites regulate airway inflammation and airway diameter. More needs to be known about the factors that regulate FeNO. There is a need for FeNO reference values for African Americans. We sought to establish reference values and identify factors associated with FeNO levels in healthy African American adults. FeNO levels were measured in 895 healthy, nonsmoking African Americans between the ages of 18 and 40 years. FeNO measurements were repeated in 84 subjects. Factors potentially associated with FeNO were measured, including blood pressure, height, weight, and serum total IgE, eosinophil cationic protein, C-reactive protein, and nitrate levels. Data on respiratory symptoms, including upper respiratory tract infection (URI) symptoms, were collected. Univariate and multivariate analyses of the relationship between these variables and FeNO levels were performed. In healthy, nonsmoking African Americans FeNO levels were stable during repeated measurements (intraclass correlation coefficient, 0.81). Sex (P < .0001), serum total IgE levels (P < .0001), and current URI symptoms (P = .0002) contributed significantly to FeNO variability but together accounted for less than 50% of the variation in FeNO levels. The high correlation between repeated measurements of FeNO and the low correlation coefficients of known factors associated with FeNO suggest that other factors might contribute substantially to variability of FeNO levels in African Americans.

  4. [The research on the airway hyperresponsiveness and IOS airway resistance index of industrial area resident].

    PubMed

    Xu, Jin; Wang, Zhen; Sun, Hongcun

    2015-09-01

    To study airway reactivity and impulse oscillation (IOS)-measured airway resistance indicators of residents of Zhenhai industrial area in Ningbo city. In the form of follow-up, both. airway reactivity and respiratory functions of populations in Zhenhai industrial zone (n = 215) and urban (n = 203) were measured, comparing difference degree between different regions. Ninty-five of 215 cases in industrial area were identified as suspected airway hyperresponsiveness, but only 43 of 203 cases were in urban areas. Forty-seven of 95 cases (49.5%) in industrial zone were positive, while only 14 cases (32.6%) in urban. The proportions of people in the two regions on different types of airway hyperresponsiveness were significantly different (P < 0.01). All airway resistance indexes of urban populations were significantly lower than that of industrial zone (P < 0.05). The prevalence of airway hyperresponsiveness and IOS airway resistance aspects of industrial area residents was higher than that of urban residents. Monitoring and evaluating the airway diseases, inflammatory lesions and respiratory function in the region were good for understanding the severe pollution in the local area in certain significance.

  5. 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. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Nasal nitric oxide is associated with exhaled NO, bronchial responsiveness and poor asthma control.

    PubMed

    Krantz, C; Janson, C; Borres, M P; Nordvall, L; Alving, K; Malinovschi, A

    2014-06-01

    The fraction of exhaled nitric oxide (FeNO) is an established marker of airway inflammation in asthma. Nasal nitric oxide (nNO) has initially been regarded as a promising marker of inflammation of nasal mucosa. However, due to its dual origins, paranasal sinuses and nasal mucosa, the clinical use of nNO is controversial. There is an inflammatory link between inflammation in the upper and lower airways within the united airways' paradigm, but the study of the clinical value of nNO in asthma has been limited. The objective of this study is to analyse nNO in asthmatics and its relationship to FeNO, bronchial hyperresponsiveness, allergic sensitization and asthma control. A total of 371 children and young adults from an asthma cohort were included in this study, which performed measurements of nNO (through aspiration at 5 mL s(-1)), FeNO, bronchial responsiveness to methacholine, blood eosinophil count (B-Eos) and IgE sensitization. The asthma control test (ACT) and a questionnaire regarding medical treatment, symptoms of asthma, rhinitis and chronic rhinosinusitis were completed by all subjects. An association was found between higher nNO levels and increased bronchial responsiveness (p < 0.001), FeNO (p < 0.001) and B-Eos (p = 0.002). Sensitization to furry animals related to higher levels of nNO (p < 0.001). Subjects with poorly controlled asthma (ACT < 15) had lower levels of nNO than subjects with a higher ACT score (619 ± 278 ppb, versus 807 ± 274 ppb, p = 0.002). Loss of smell showed the strongest association with lower nNO levels among the upper airway symptoms recorded. In patients with asthma, nNO was positively correlated with exhaled NO, bronchial responsiveness and asthma control. This study suggests clinical utility of nNO in subjects with asthma, but in order to get better understanding of the nNO determinants, simultaneous mapping of upper airway comorbidities by clinical examination is appropriate.

  7. Molecular modulation of airway epithelial ciliary response to sneezing.

    PubMed

    Zhao, Ke-Qing; Cowan, Andrew T; Lee, Robert J; Goldstein, Natalia; Droguett, Karla; Chen, Bei; Zheng, Chunquan; Villalon, Manuel; Palmer, James N; Kreindler, James L; Cohen, Noam A

    2012-08-01

    Our purpose was to evaluate the effect of the mechanical force of a sneeze on sinonasal cilia function and determine the molecular mechanism responsible for eliciting the ciliary response to a sneeze. A novel model was developed to deliver a stimulation simulating a sneeze (55 mmHg for 50 ms) at 26°C to the apical surface of mouse and human nasal epithelial cells. Ciliary beating was visualized, and changes in ciliary beat frequency (CBF) were determined. To interrogate the molecular cascades driving sneeze-induced changes of CBF, pharmacologic manipulation of intra- and extracellular calcium, purinergic, PKA, and nitric oxide (NO) signaling were performed. CBF rapidly increases by ≥150% in response to a sneeze, which is dependent on the release of adenosine triphosphate (ATP), calcium influx, and PKA activation. Furthermore, apical release of ATP is independent of calcium influx, but calcium influx and subsequent increase in CBF are dependent on the ATP release. Lastly, we observed a blunted ciliary response in surgical specimens derived from patients with chronic rhinosinusitis compared to control patients. Apical ATP release with subsequent calcium mobilization and PKA activation are involved in sinonasal ciliary response to sneezing, which is blunted in patients with upper-airway disease.

  8. Effects of multiday exposure to ozone on airway inflammation as determined using sputum induction.

    PubMed

    Ratto, Jeffrey; Wong, Hofer; Liu, Jane; Fahy, John; Boushey, Homer; Solomon, Colin; Balmes, John

    2006-02-01

    Single short-term exposures to ozone are known to cause acute changes in pulmonary function and neutrophilic airway inflammation. The respiratory health effects of repeated exposures are not as well studied. Pulmonary function decrements are known to attenuate, but it is less clear how injury and inflammation are affected. Using sputum induction (SI) to sample respiratory tract lining fluid after single- and multiday exposures, we designed a study to test the hypothesis that neutrophils would increase after multiday exposure compared with single-day exposure. In a randomized, crossover design, 15 normal healthy subjects were exposed to O3 (0.2 ppm) under two conditions: for 4 hr for 1 day (1D) and for 4 hr for 4 consecutive days (4D). Pulmonary function testing was performed immediately before and after each 4-hr exposure. The SI was performed 18 hr after the end of the 1D and 4D conditions. The symptom and pulmonary function data followed a pattern seen in other multiday O3 exposure studies, with the greatest changes occurring on the second day. In contrast to previous studies using bronchoalveolar lavage, however, there was a significant increase in the percentage of neutrophils and a significant decrease in the percentage of macrophages after the 4D condition compared with the 1D condition. Given that SI likely samples proximal airways better than distal lung, these results add to the body of evidence that differential airway compartmental responses to O3 occur in humans and other species.

  9. Effects of Multiday Exposure to Ozone on Airway Inflammation as Determined Using Sputum Induction

    PubMed Central

    Ratto, Jeffrey; Wong, Hofer; Liu, Jane; Fahy, John; Boushey, Homer; Solomon, Colin; Balmes, John

    2006-01-01

    Single short-term exposures to ozone are known to cause acute changes in pulmonary function and neutrophilic airway inflammation. The respiratory health effects of repeated exposures are not as well studied. Pulmonary function decrements are known to attenuate, but it is less clear how injury and inflammation are affected. Using sputum induction (SI) to sample respiratory tract lining fluid after single- and multiday exposures, we designed a study to test the hypothesis that neutrophils would increase after multiday exposure compared with single-day exposure. In a randomized, crossover design, 15 normal healthy subjects were exposed to O3 (0.2 ppm) under two conditions: for 4 hr for 1 day (1D) and for 4 hr for 4 consecutive days (4D). Pulmonary function testing was performed immediately before and after each 4-hr exposure. The SI was performed 18 hr after the end of the 1D and 4D conditions. The symptom and pulmonary function data followed a pattern seen in other multiday O3 exposure studies, with the greatest changes occurring on the second day. In contrast to previous studies using bronchoalveolar lavage, however, there was a significant increase in the percentage of neutrophils and a significant decrease in the percentage of macrophages after the 4D condition compared with the 1D condition. Given that SI likely samples proximal airways better than distal lung, these results add to the body of evidence that differential airway compartmental responses to O3 occur in humans and other species. PMID:16451856

  10. Interaction of Ambient Air Pollution With Asthma Medication on Exhaled Nitric Oxide Among Asthmatics

    PubMed Central

    Qian, Zhengmin; Lin, Hung-Mo; Chinchilli, Vernon M.; Lehman, Erik B.; Duan, Yinkang; Craig, Timothy J.; Wilson, William E.; Liao, Duanping; Lazarus, Stephen C.; Bascom, Rebecca

    2013-01-01

    The interaction between ambient air pollution and asthma medication remains unclear. The authors compared airway inflammation response to air pollution among asthmatics. Increases of 10 ppb of nitrogen dioxide (NO2) and of 10 μg/m3 of particulate matter < 10 micron in diameter (PM10) daily concentrations were associated with an increase in exhaled nitric oxide (eNO) of 0.13 ppb (95% confidence interval = 0.06, 0.19) and of 0.07 ppb (95% confidence interval = 0.02, 0.12), respectively, in models adjusted for important covariates. The results show that the medication could not counteract airway inflammation effects of air pollution. Specifically, the patients on triamcinolone decreased the sensitivity to PM10 but increased the sensitivity to NO2. The patients on salmeterol were more vulnerable to both NO2 and PM10. This study indicates that the current pollution levels may still enhance airway inflammation among patients with persistent asthma even when they are on asthma medications. PMID:19864219

  11. Proteinase activated receptor-2-mediated dual oxidase-2 up-regulation is involved in enhanced airway reactivity and inflammation in a mouse model of allergic asthma.

    PubMed

    Nadeem, Ahmed; Alharbi, Naif O; Vliagoftis, Harissios; Tyagi, Manoj; Ahmad, Sheikh F; Sayed-Ahmed, Mohamed M

    2015-07-01

    Airway epithelial cells (AECs) express a variety of receptors, which sense danger signals from various aeroallergens/pathogens being inhaled constantly. Proteinase-activated receptor 2 (PAR-2) is one such receptor and is activated by cockroach allergens, which have intrinsic serine proteinase activity. Recently, dual oxidases (DUOX), especially DUOX-2, have been shown to be involved in airway inflammation in response to Toll-like receptor activation. However, the association between PAR-2 and DUOX-2 has not been explored in airways of allergic mice. Therefore, this study investigated the contribution of DUOX-2/reactive oxygen species (ROS) signalling in airway reactivity and inflammation after PAR-2 activation. Mice were sensitized intraperitoneally with intact cockroach allergen extract (CE) in the presence of aluminium hydroxide followed by intranasal challenge with CE. Mice were then assessed for airway reactivity, inflammation, oxidative stress (DUOX-2, ROS, inducible nitric oxide synthase, nitrite, nitrotyrosine and protein carbonyls) and apoptosis (Bax, Bcl-2, caspase-3). Challenge with CE led to up-regulation of DUOX-2 and ROS in AECs with concomitant increases in airway reactivity/inflammation and parameters of oxidative stress, and apoptosis. All of these changes were significantly inhibited by intranasal administration of ENMD-1068, a small molecule antagonist of PAR-2 in allergic mice. Administration of diphenyliodonium to allergic mice also led to improvement of allergic airway responses via inhibition of the DUOX-2/ROS pathway; however, these effects were less pronounced than PAR-2 antagonism. The current study suggests that PAR-2 activation leads to up-regulation of the DUOX-2/ROS pathway in AECs, which is involved in regulation of airway reactivity and inflammation via oxidative stress and apoptosis.

  12. Elbow Position Affects Distal Radioulnar Joint Kinematics

    PubMed Central

    Fu, Eric; Li, Guoan; Souer, Sebastiaan; Lozano-Calderon, Santiago; Herndon, James H.; Jupiter, Jesse B.; Chen, Neal C.

    2009-01-01

    Previous in vivo and in vitro studies of forearm supination/pronation suggest that distal radioulnar joint kinematics may be affected by elbow flexion. The primary hypotheses tested by this study were that in vivo: 1) ulnar variance changes with elbow flexion and forearm rotation and 2) the arc of forearm rotation changes in relationship to elbow flexion. Materials and Methods Changes in radioulnar kinematics during forearm supination/pronation and elbow flexion (0–90°) were studied in five uninjured subjects using computed tomography, dual-orthogonal fluoroscopy, and three-dimensional modeling. Analysis of variance and post-hoc testing was performed. Results Proximal translation of the radius was greatest with the elbow flexed to 90° with the arm in mid-pronation. With the arm in mid-pronation, the translation of the radius was significantly greater at 0° versus 45° of elbow flexion (0.82 ± 0.59 mm v. 0.65 ± 0.80 mm, F: 4.49, Post Hoc: 0.055; p = 0.05), and significantly smaller at 45° versus 90° of elbow flexion (0.65 ± 0.80 mm v. 0.97 ± 0.35 mm, F: 4.49, Post Hoc: 0.048; p = 0.05). Proximal translation of the radius in mid-pronation was significantly greater than when the forearm was in a supinated position when the elbow was at 0° or 90° flexion (F: 14.90, post-hoc: < 0.01; p < 0.01, F: 19.11, post-hoc: < 0.01, p < 0.01). The arc of forearm rotation was significantly decreased at 0° compared to 90° of elbow flexion (129.3 ± 22.2° v 152.8 ± 14.4°, F: 3.29, post-hoc: 0.79; p = 0.09). The center of rotation shifted volarly and ulnarly with increasing elbow extension. Discussion Elbow position affects the kinematics of the distal radioulnar joint. The kinematics of the distal radioulnar joint are primarily affected by forearm rotation and secondarily affected by elbow flexion. These findings have clinical relevance to our understanding of ulnar impaction, and how elbow position affects the proximal-distal translation of the radius. These

  13. Normal values of offline exhaled and nasal nitric oxide in healthy children and teens using chemiluminescence.

    PubMed

    Menou, A; Babeanu, D; Paruit, H N; Ordureau, A; Guillard, S; Chambellan, A

    2017-08-21

    Nitric oxide (NO) can be used to detect respiratory or ciliary diseases. Fractional exhaled nitric oxide (FeNO) measurement can reflect ongoing eosinophilic airway inflammation and has a diagnostic utility as a test for asthma screening and follow-up while nasal nitric oxide (nNO) is a valuable screening tool for the diagnosis of primary ciliary dyskinesia. The possibility of collecting airway gas samples in an offline manner offers the advantage to extend these measures and improve the screening and management of these diseases, but normal values from healthy children and teens remain sparse. Samples were consecutively collected using the offline method for eNO and nNO chemiluminescence measurement in 88 and 31 healthy children and teens, respectively. Offline eNO measurement was also performed in 30 consecutive children with naïve asthma and/or respiratory allergy. The normal offline eNO value was determined by the following regression equation -8.206 + 0.176 × height. The upper limit of the norm for the offline eNO value was 27.4 parts per billion (ppb). A separate analysis was performed in children, pre-teens and teens, for which offline eNO was 13.6 ± 4.7 ppb, 16.3 ± 13.7 ppb and 20.0 ± 7.2 ppb, respectively. The optimal cut-off value of the offline eNO to predict asthma or respiratory allergies was 23.3 ppb, with a sensitivity and specificity of 77% and 91%, respectively. Mean offline nNO was determined at 660 ppb with the lower limit of the norm at 197 ppb. The use of offline eNO and nNO normal values should favour the widespread screening of respiratory diseases in children of school age in their usual environment.

  14. Nitric oxide fumigation for postharvest pest control

    USDA-ARS?s Scientific Manuscript database

    Nitric oxide fumigation is effective against all arthropod pests at various life stages tested. Nine insect pests at various life stages and bulb mites were subjected to nitric oxide fumigation treatments under ultralow oxygen conditions of =50 ppm O2 in 1.9L glass jars as fumigation chambers. The ...

  15. The nitric oxide producing reactions of hydroxyurea.

    PubMed

    King, S Bruce

    2003-03-01

    Hydroxyurea is used to treat a variety of cancers and sickle cell disease. Despite this widespread use, a complete mechanistic understanding of the beneficial actions of this compound remains to be understood. Hydroxyurea inhibits ribonucleotide reductase and increases the levels of fetal hemoglobin, which explains a portion of the effects of this drug. Administration of hydroxyurea to patients results in a significant increase in levels of iron nitrosyl hemoglobin, nitrite and nitrate suggesting the in vivo metabolism of hydroxyurea to nitric oxide. Formation of nitric oxide from hydroxyurea may explain a portion of the observed effects of hydroxyurea treatment. At the present, the mechanism or mechanisms of nitric oxide release, the identity of the in vivo oxidant and the site of metabolism remain to be identified. Chemical oxidation of hydroxyurea produces nitric oxide and nitroxyl, the one-electron reduced form of nitric oxide. These oxidative pathways generally proceed through the nitroxide radical (2) or C-nitrosoformamide (3). Biological oxidants, including both iron and copper containing enzymes and proteins, also convert hydroxyurea to nitric oxide or its decomposition products in vitro and these reactions also occur through these intermediates. A number of other reactions of hydroxyurea including the reaction with ribonucleotide reductase and irradiation demonstrate the potential to release nitric oxide and should be further investigated. Gaining an understanding of the metabolism of hydroxyurea to nitric oxide will provide valuable information towards the treatment of these disorders and may lead to the development of better therapeutic agents.

  16. 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 ...

  17. 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 ...