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Sample records for airway mucus obstruction

  1. In Vitro Microfluidic Models of Mucus-Like Obstructions in Small Airways

    NASA Astrophysics Data System (ADS)

    Mulligan, Molly K.; Grotberg, James B.; Sznitman, Josué

    2012-11-01

    Liquid plugs can form in the lungs as a result of a host of different diseases, including cystic fibrosis and chronic obstructive pulmonary disease. The existence of such fluid obstructions have been found as far down in the bronchiole tree as the sixteenth generation, where bronchiole openings have diameters on the order of a hundred to a few hundred microns. Understanding the propagation of liquid plugs within the bifurcating branches of bronchiole airways is important because their presence in the lungs, and their rupture and break-up, can cause injury to the epithelial cells lining the airway walls as a result of high wall shear stresses. In particular, liquid plug rupture and break-up frequently occurs at airway bifurcations. Until present, however, experimental studies of liquid plugs have generally been restricted to Newtonian fluids that do not reflect the actual pseudoplastic properties of lung mucus. The present work attempts to uncover the propagation, rupture and break-up of mucus-like liquid plugs in the lower generations of the airway tree using microfluidic models. Our approach allows the dynamics of mucus-like plug break-up to be studied in real-time, in a one-to-one in vitro model, as a function of mucus rheology and bronchial tree geometry.

  2. Airway mucus obstruction triggers macrophage activation and matrix metalloproteinase 12-dependent emphysema.

    PubMed

    Trojanek, Joanna B; Cobos-Correa, Amanda; Diemer, Stefanie; Kormann, Michael; Schubert, Susanne C; Zhou-Suckow, Zhe; Agrawal, Raman; Duerr, Julia; Wagner, Claudius J; Schatterny, Jolanthe; Hirtz, Stephanie; Sommerburg, Olaf; Hartl, Dominik; Schultz, Carsten; Mall, Marcus A

    2014-11-01

    Whereas cigarette smoking remains the main risk factor for emphysema, recent studies in β-epithelial Na(+) channel-transgenic (βENaC-Tg) mice demonstrated that airway surface dehydration, a key pathophysiological mechanism in cystic fibrosis (CF), caused emphysema in the absence of cigarette smoke exposure. However, the underlying mechanisms remain unknown. The aim of this study was to elucidate mechanisms of emphysema formation triggered by airway surface dehydration. We therefore used expression profiling, genetic and pharmacological inhibition, Foerster resonance energy transfer (FRET)-based activity assays, and genetic association studies to identify and validate emphysema candidate genes in βENaC-Tg mice and patients with CF. We identified matrix metalloproteinase 12 (Mmp12) as a highly up-regulated gene in lungs from βENaC-Tg mice, and demonstrate that elevated Mmp12 expression was associated with progressive emphysema formation, which was reduced by genetic deletion and pharmacological inhibition of MMP12 in vivo. By using FRET reporters, we show that MMP12 activity was elevated on the surface of airway macrophages in bronchoalveolar lavage from βENaC-Tg mice and patients with CF. Furthermore, we demonstrate that a functional polymorphism in MMP12 (rs2276109) was associated with severity of lung disease in CF. Our results suggest that MMP12 released by macrophages activated on dehydrated airway surfaces may play an important role in emphysema formation in the absence of cigarette smoke exposure, and may serve as a therapeutic target in CF and potentially other chronic lung diseases associated with airway mucus dehydration and obstruction. PMID:24828142

  3. Mechanosensitive ATP Release Maintains Proper Mucus Hydration of Airways

    PubMed Central

    Button, Brian; Okada, Seiko F.; Frederick, Charles Brandon; Thelin, William R.; Boucher, Richard C.

    2013-01-01

    The clearance of mucus from the airways protects the lungs from inhaled noxious and infectious materials. Proper hydration of the mucus layer enables efficient mucus clearance through beating of cilia on airway epithelial cells, and reduced clearance of excessively concentrated mucus occurs in patients with chronic obstructive pulmonary disease and cystic fibrosis. Key steps in the mucus transport process are airway epithelia sensing and responding to changes in mucus hydration. We reported that extracellular adenosine triphosphate (ATP) and adenosine were important luminal auto-crine and paracrine signals that regulated the hydration of the surface of human airway epithelial cultures through their action on apical membrane purinoceptors. Mucus hydration in human airway epithelial cultures was sensed by an interaction between cilia and the overlying mucus layer: Changes in mechanical strain, proportional to mucus hydration, regulated ATP release rates, adjusting fluid secretion to optimize mucus layer hydration. This system provided a feedback mechanism by which airways maintained mucus hydration in an optimum range for cilia propulsion. Understanding how airway epithelia can sense and respond to changes in mucus properties helps us to understand how the mucus clearance system protects the airways in health and how it fails in lung diseases such as cystic fibrosis. PMID:23757023

  4. Mechanosensitive ATP release maintains proper mucus hydration of airways.

    PubMed

    Button, Brian; Okada, Seiko F; Frederick, Charles Brandon; Thelin, William R; Boucher, Richard C

    2013-06-11

    The clearance of mucus from the airways protects the lungs from inhaled noxious and infectious materials. Proper hydration of the mucus layer enables efficient mucus clearance through beating of cilia on airway epithelial cells, and reduced clearance of excessively concentrated mucus occurs in patients with chronic obstructive pulmonary disease and cystic fibrosis. Key steps in the mucus transport process are airway epithelia sensing and responding to changes in mucus hydration. We reported that extracellular adenosine triphosphate (ATP) and adenosine were important luminal autocrine and paracrine signals that regulated the hydration of the surface of human airway epithelial cultures through their action on apical membrane purinoceptors. Mucus hydration in human airway epithelial cultures was sensed by an interaction between cilia and the overlying mucus layer: Changes in mechanical strain, proportional to mucus hydration, regulated ATP release rates, adjusting fluid secretion to optimize mucus layer hydration. This system provided a feedback mechanism by which airways maintained mucus hydration in an optimum range for cilia propulsion. Understanding how airway epithelia can sense and respond to changes in mucus properties helps us to understand how the mucus clearance system protects the airways in health and how it fails in lung diseases such as cystic fibrosis. PMID:23757023

  5. 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

  6. Unplugging Mucus in Cystic Fibrosis and Chronic Obstructive Pulmonary Disease.

    PubMed

    Mall, Marcus A

    2016-04-01

    Airway mucus obstruction is a key feature of cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD). The thin layer of mucus that covers healthy airway surfaces has important protective functions in lung defense. However, excess mucus produces airflow obstruction and provides a nidus for bacterial infection and inflammation. Despite its importance in pathogenesis, understanding of the mechanisms underlying airway mucus obstruction, as well as therapeutic options, remain limited. Studies in the rare genetic disease CF identified airway surface dehydration due to cystic fibrosis transmembrane conductance regulator (CFTR) gene dysfunction as an important disease mechanism that may explain mucus stasis and plugging in a spectrum of muco-obstructive lung diseases, including COPD. This concept is supported by the phenotype of the β-epithelial Na(+) channel-transgenic mouse that exhibits airway surface dehydration and develops a spontaneous lung disease that shares key features with CF and COPD, such as airway mucus plugging, chronic neutrophilic inflammation, and structural lung damage. Furthermore, preclinical testing demonstrated that hydration strategies, including osmotically active hypertonic saline and preventive inhibition of the amiloride-sensitive epithelial Na(+) channel are effective in unplugging airways in this mouse model of chronic obstructive lung disease. On the other hand, genetic deletion of neutrophil elastase, a potent stimulus for mucus hypersecretion, reduced goblet cell metaplasia and mucin expression but had no effect on mucus obstruction in vivo. Collectively, these studies demonstrate that airway surface dehydration is sufficient to produce mucus obstruction even in the absence of mucus hypersecretion and support further clinical testing of hydrating agents as a promising therapeutic strategy to unplug mucus in CF and COPD. PMID:27115954

  7. Brachycephalic airway obstructive syndrome.

    PubMed

    Wykes, P M

    1991-06-01

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

  8. A Biophysical Basis for Mucus Solids Concentration as a Candidate Biomarker for Airways Disease

    PubMed Central

    Hill, David B.; Vasquez, Paula A.; Mellnik, John; McKinley, Scott A.; Vose, Aaron; Mu, Frank; Henderson, Ashley G.; Donaldson, Scott H.; Alexis, Neil E.; Boucher, Richard C.; Forest, M. Gregory

    2014-01-01

    In human airways diseases, including cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD), host defense is compromised and airways inflammation and infection often result. Mucus clearance and trapping of inhaled pathogens constitute key elements of host defense. Clearance rates are governed by mucus viscous and elastic moduli at physiological driving frequencies, whereas transport of trapped pathogens in mucus layers is governed by diffusivity. There is a clear need for simple and effective clinical biomarkers of airways disease that correlate with these properties. We tested the hypothesis that mucus solids concentration, indexed as weight percent solids (wt%), is such a biomarker. Passive microbead rheology was employed to determine both diffusive and viscoelastic properties of mucus harvested from human bronchial epithelial (HBE) cultures. Guided by sputum from healthy (1.5–2.5 wt%) and diseased (COPD, CF; 5 wt%) subjects, mucus samples were generated in vitro to mimic in vivo physiology, including intermediate range wt% to represent disease progression. Analyses of microbead datasets showed mucus diffusive properties and viscoelastic moduli scale robustly with wt%. Importantly, prominent changes in both biophysical properties arose at ∼4 wt%, consistent with a gel transition (from a more viscous-dominated solution to a more elastic-dominated gel). These findings have significant implications for: (1) penetration of cilia into the mucus layer and effectiveness of mucus transport; and (2) diffusion vs. immobilization of micro-scale particles relevant to mucus barrier properties. These data provide compelling evidence for mucus solids concentration as a baseline clinical biomarker of mucus barrier and clearance functions. PMID:24558372

  9. The role of airway mucus in pulmonary toxicology.

    PubMed Central

    Samet, J M; Cheng, P W

    1994-01-01

    Airway mucus is a complex airway secretion whose primary function as part of the mucociliary transport mechanism is to to serve as renewable and transportable barrier against inhaled particulates and toxic agents. The rheologic properties necessary for this function are imparted by glycoproteins, or mucins. Some respiratory disease states, e.g., asthma, cystic fibrosis, and bronchitis, are characterized by quantitative and qualitative changes in mucus biosynthesis that contribute to pulmonary pathology. Similar alterations in various aspects of mucin biochemistry and biophysics, leading to mucus hypersecretion and altered mucus rheology, result from inhalation of certain air pollutants, such as ozone, sulfur dioxide, nitrogen dioxide, and cigarette smoke. The consequences of these pollutant-induced alterations in mucus biology are discussed in the context of pulmonary pathophysiology and toxicology. PMID:7925190

  10. Automated detection of presence of mucus foci in airway diseases: preliminary results

    NASA Astrophysics Data System (ADS)

    Odry, Benjamin L.; Kiraly, Atilla P.; Novak, Carol L.; Naidich, David P.; Ko, Jane; Godoy, Myrna C. B.

    2009-02-01

    Chronic Obstructive Pulmonary Disease (COPD) is often characterized by partial or complete obstruction of airflow in the lungs. This can be due to airway wall thickening and retained secretions, resulting in foci of mucoid impactions. Although radiologists have proposed scoring systems to assess extent and severity of airway diseases from CT images, these scores are seldom used clinically due to impracticality. The high level of subjectivity from visual inspection and the sheer number of airways in the lungs mean that automation is critical in order to realize accurate scoring. In this work we assess the feasibility of including an automated mucus detection method in a clinical scoring system. Twenty high-resolution datasets of patients with mild to severe bronchiectasis were randomly selected, and used to test the ability of the computer to detect the presence or absence of mucus in each lobe (100 lobes in all). Two experienced radiologists independently scored the presence or absence of mucus in each lobe based on the visual assessment method recommended by Sheehan et al [1]. These results were compared with an automated method developed for mucus plug detection [2]. Results showed agreement between the two readers on 44% of the lobes for presence of mucus, 39% of lobes for absence of mucus, and discordant opinions on 17 lobes. For 61 lobes where 1 or both readers detected mucus, the computer sensitivity was 75.4%, the specificity was 69.2%, and the positive predictive value (PPV) was 79.3%. Six computer false positives were a-posteriori reviewed by the experts and reassessed as true positives, yielding results of 77.6% sensitivity, 81.8% for specificity, and 89.6% PPV.

  11. Airway obstruction with cricoid pressure.

    PubMed

    Hartsilver, E L; Vanner, R G

    2000-03-01

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

  12. Role of Mechanical Stress in Regulating Airway Surface Hydration and Mucus Clearance Rates

    PubMed Central

    Button, Brian; Boucher, Richard C.

    2008-01-01

    Effective clearance of mucus is a critical innate airway defense mechanism, and under appropriate conditions, can be stimulated to enhance clearance of inhaled pathogens. It has become increasingly clear that extracellular nucleotides (ATP and UTP) and nucleosides (adenosine) are important regulators of mucus clearance in the airways as a result of their ability to stimulate fluid secretion, mucus hydration, and cilia beat frequency (CBF). One ubiquitous mechanism to stimulate ATP release is through external mechanical stress. This article addresses the role of physiologically-relevant mechanical forces in the lung and their effects on regulating mucociliary clearance (MCC). The effects of mechanical forces on the stimulating ATP release, fluid secretion, CBF, and MCC are discussed. Also discussed is evidence suggesting that airway hydration and stimulation of MCC by stress-mediated ATP release may play a role in several therapeutic strategies directed at improving mucus clearance in patients with obstructive lung diseases, including cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD). PMID:18585484

  13. Transient motion of mucus plugs in respiratory airways

    NASA Astrophysics Data System (ADS)

    Zamankhan, Parsa; Hu, Yingying; Helenbrook, Brian; Takayama, Shuichi; Grotberg, James B.

    2011-11-01

    Airway closure occurs in lung diseases such as asthma, cystic fibrosis, or emphysema which have an excess of mucus that forms plugs. The reopening process involves displacement of mucus plugs in the airways by the airflow of respiration. Mucus is a non-Newtonian fluid with a yield stress; therefore its behavior can be approximated by a Bingham fluid constitutive equation. In this work the reopening process is approximated by simulation of a transient Bingham fluid plug in a 2D channel. The governing equations are solved by an Arbitrary Lagrangian Eulerian (ALE) finite element method through an in-house code. The constitutive equation for the Bingham fluid is implemented through a regularization method. The effects of the yield stress on the flow features and wall stresses are discussed with applications to potential injuries to the airway epithelial cells which form the wall. The minimum driving pressure for the initiation of the motion is computed and its value is related to the mucus properties and the plug shape. Supported by HL84370 and HL85156.

  14. CFTR, Mucins, and Mucus Obstruction in Cystic Fibrosis

    PubMed Central

    Kreda, Silvia M.; Davis, C. William; Rose, Mary Callaghan

    2012-01-01

    Mucus pathology in cystic fibrosis (CF) has been known for as long as the disease has been recognized and is sometimes called mucoviscidosis. The disease is marked by mucus hyperproduction and plugging in many organs, which are usually most fatal in the airways of CF patients, once the problem of meconium ileus at birth is resolved. After the CF gene, CFTR, was cloned and its protein product identified as a cAMP-regulated Cl− channel, causal mechanisms underlying the strong mucus phenotype of the disease became obscure. Here we focus on mucin genes and polymeric mucin glycoproteins, examining their regulation and potential relationships to a dysfunctional cystic fibrosis transmembrane conductance regulator (CFTR). Detailed examination of CFTR expression in organs and different cell types indicates that changes in CFTR expression do not always correlate with the severity of CF disease or mucus accumulation. Thus, the mucus hyperproduction that typifies CF does not appear to be a direct cause of a defective CFTR but, rather, to be a downstream consequence. In organs like the lung, up-regulation of mucin gene expression by inflammation results from chronic infection; however, in other instances and organs, the inflammation may have a non-infectious origin. The mucus plugging phenotype of the β-subunit of the epithelial Na+ channel (βENaC)-overexpressing mouse is proving to be an archetypal example of this kind of inflammation, with a dehydrated airway surface/concentrated mucus gel apparently providing the inflammatory stimulus. Data indicate that the luminal HCO3 − deficiency recently described for CF epithelia may also provide such a stimulus, perhaps by causing a mal-maturation of mucins as they are released onto luminal surfaces. In any event, the path between CFTR dysfunction and mucus hyperproduction has proven tortuous, and its unraveling continues to offer its own twists and turns, along with fascinating glimpses into biology. PMID:22951447

  15. Direct effects of interleukin-13 on epithelial cells cause airway hyperreactivity and mucus overproduction in asthma.

    PubMed

    Kuperman, Douglas A; Huang, Xiaozhu; Koth, Laura L; Chang, Grace H; Dolganov, Gregory M; Zhu, Zhou; Elias, Jack A; Sheppard, Dean; Erle, David J

    2002-08-01

    Asthma is an increasingly common disease that remains poorly understood and difficult to manage. This disease is characterized by airway hyperreactivity (AHR, defined by exaggerated airflow obstruction in response to bronchoconstrictors), mucus overproduction and chronic eosinophilic inflammation. AHR and mucus overproduction are consistently linked to asthma symptoms and morbidity. Asthma is mediated by Th2 lymphocytes, which produce a limited repertoire of cytokines, including interleukin-4 (IL-4), IL-5, IL-9 and IL-13. Although each of these cytokines has been implicated in asthma, IL-13 is now thought to be especially critical. In animal models of allergic asthma, blockade of IL-13 markedly inhibits allergen-induced AHR, mucus production and eosinophilia. Furthermore, IL-13 delivery to the airway causes all of these effects. IL-13 is thus both necessary and sufficient for experimental models of asthma. However, the IL-13-responsive cells causing these effects have not been identified. Here we show that mice lacking signal transducer and activator of transcription 6 (STAT6) were protected from all pulmonary effects of IL-13. Reconstitution of STAT6 only in epithelial cells was sufficient for IL-13-induced AHR and mucus production in the absence of inflammation, fibrosis or other lung pathology. These results demonstrate the importance of direct effects of IL-13 on epithelial cells in causing two central features of asthma. PMID:12091879

  16. Continuity of airway goblet cells and intraluminal mucus in the airways of patients with bronchial asthma.

    PubMed

    Shimura, S; Andoh, Y; Haraguchi, M; Shirato, K

    1996-07-01

    The aim of this study was to elucidate the mechanism of the formation of the widespread mucous-plugging observed in autopsied lungs from patients with bronchial asthma. We performed morphometric analysis of airways of autopsied lungs from eight patients with bronchial asthma (Group BA), and compared it with those of six chronic bronchitics (Group CB) and four control patients (Control). The following parameters were measured in paraffin sections: volume proportion of bronchial glands to bronchial wall (Gland%); goblet cell granules to total epithelial layer (Goblet %); intraluminal mucus expressed as the mucus occupying ratio (MOR); volume ratio of intraluminal mucus continuous with goblet cells to total intraluminal mucus (Vc/Vtol %); and surface ratio of the contact surface of intraluminal mucus continuous with goblet cells to the total luminal surface (Sc/Stot %). Gland%, Goblet %, and MOR or inflammatory cell numbers in the airway walls both from Group BA and CB were larger than those from the Control group. However, no significant differences were observed between Group BA and CB in Gland%, Goblet %, MOR or inflammatory cell numbers, except for the eosinophil number: i.e. 23 +/- 3, 22 +/- 3 and 6 +/- 2% in Gland%; 22 +/- 9, 5 +/- 4 and 2 +/- 2% in Goblet%; 10 +/- 3, 18 +/- 3 and 0.3 +/- 0.5% in MOR; 199 +/- 68, 10 +/- 3 and 2 +/- 2 cells. mm-2 in eosinophil number of the peripheral airways from Groups BA, CB and Control, respectively. In contrast, marked and significant increases were observed both in Vc/Vtot% and Sc/Stot% in Group BA compared to Groups CB and Control both in central and peripheral airways: i.e. Vc/Vtot% in the peripheral airways was 53 +/- 5, 4 +/- 3 and 0.8 +/- 0.8% from Groups BA, CB and Control, respectively (BA vs CB or BA vs Control, p < 0.01 each). These findings suggest that the continuity of goblet cells and intraluminal mucus or lack of full release of mucus, from goblet cells, is peculiar to asthmatic airways, and may contribute to

  17. Anaesthetic management of acute airway obstruction

    PubMed Central

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

    2016-01-01

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

  18. Anaesthetic management of acute airway obstruction.

    PubMed

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

    2016-03-01

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

  19. Therapeutic bronchoscopic interventions for malignant airway obstruction

    PubMed Central

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

    2016-01-01

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

  20. Effects of reduced mucus oxygen concentration in airway Pseudomonas infections of cystic fibrosis patients

    PubMed Central

    Worlitzsch, Dieter; Tarran, Robert; Ulrich, Martina; Schwab, Ute; Cekici, Aynur; Meyer, Keith C.; Birrer, Peter; Bellon, Gabriel; Berger, Jürgen; Weiss, Tilo; Botzenhart, Konrad; Yankaskas, James R.; Randell, Scott; Boucher, Richard C.; Döring, Gerd

    2002-01-01

    Current theories of CF pathogenesis predict different predisposing “local environmental” conditions and sites of bacterial infection within CF airways. Here we show that, in CF patients with established lung disease, Psuedomonas aeruginosa was located within hypoxic mucopurulent masses in airway lumens. In vitro studies revealed that CF-specific increases in epithelial O2 consumption, linked to increased airway surface liquid (ASL) volume absorption and mucus stasis, generated steep hypoxic gradients within thickened mucus on CF epithelial surfaces prior to infection. Motile P. aeruginosa deposited on CF airway surfaces penetrated into hypoxic mucus zones and responded to this environment with increased alginate production. With P. aeruginosa growth in oxygen restricted environments, local hypoxia was exacerbated and frank anaerobiosis, as detected in vivo, resulted. These studies indicate that novel therapies for CF include removal of hypoxic mucus plaques and antibiotics effective against P. aeruginosa adapted to anaerobic environments. PMID:11827991

  1. Investigation of mucus transport in an idealized lung airway model using multiphase CFD analysis

    NASA Astrophysics Data System (ADS)

    Rajendran, Rahul; Banerjee, Arindam

    2015-11-01

    Mucus, a Bingham fluid is transported in the pulmonary airways by consistent beating of the cilia and exhibits a wide range of physical properties in response to the core air flow and various pathological conditions. A better understanding of the interfacial instability is required as it plays a crucial role in gas transport, mixing, mucus clearance and drug delivery. In the current study, mucus is modelled as a Newtonian fluid and the two phase gas-liquid flow in the airways is investigated using an inhomogeneous Eulerian-Eulerian approach. The complex interface between the phases is tracked using the conventional VOF (Volume of Fluid) method. Results from our CFD simulations which are performed in idealized single and double bifurcation geometries will be presented and the influence of airflow rate, mucus layer thickness, mucus viscosity, airway geometry (branching & diameter) and surface tension on mucus flow behavior will be discussed. Mean mucus layer thickness, pressure drop due to momentum transfer & increased airway resistance, mucus transport speed and the flow morphology will be compared to existing experimental and theoretical data.

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

    PubMed

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

    2016-01-01

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

  3. β2-Adrenoceptor involved in smoking-induced airway mucus hypersecretion through β-arrestin-dependent signaling.

    PubMed

    Zhou, Yujiao; Zhang, Yuan; Guo, Yang; Zhang, Youyi; Xu, Ming; He, Bei

    2014-01-01

    Progression of chronic obstructive pulmonary disease is associated with small airway obstruction by accumulation of inflammatory mucous exudates. However, the mechanism of mucin hypersecretion after exposure to cigarette smoke (CS) is still not clear. In this study, we explored the contribution of β2-adrenoceptor (β2-AR) signaling to CS extract (CSE)-induced mucus hypersecretion in vitro and examined the effect of a β-blocker on airway mucin hypersecretion in vivo. NCI-H292 epithelial cell line was used to determine the contribution of β2-AR signaling to CSE-induced MUC5AC production by treatment with β2-AR antagonists propranolol and ICI118551 and β2-AR-targeted small interfering RNA. The effect of propranolol on airway mucus hypersecretion was examined in a rat model exposed to CS. MUC5AC expression was assayed by real-time PCR, immunohistochemistry and ELISA. β2-AR and its downstream signaling were detected by western blot analysis. We found that pretreating NCI-H292 cells with propranolol, ICI118551 for 30 min or β2AR-targeted siRNA for 48 h reduced MUC5AC mRNA and protein levels stimulated by CSE. However,inhibiting the classical β2AR-cAMP-PKA pathway didn't attenuate CSE-induced MUC5AC production, while silencing β-arretin2 expression significantly decreased ERK and p38MAPK phosphorylation, thus reduced the CSE-stimulated MUC5AC production. In vivo, we found that administration of propranolol (25 mg kg(-1) d(-1)) for 28 days significantly attenuated the airway goblet cell metaplasia, mucus hypersecretion and MUC5AC expression of rats exposed to CS. From the study, β2-AR-β-arrestin2-ERK1/2 signaling was required for CS-induced airway MUC5AC expression. Chronic propranolol administration ameliorated airway mucus hypersecretion and MUC5AC expression in smoking rats. The exploration of these mechanisms may contribute to the optimization of β2-AR target therapy in chronic obstructive pulmonary disease. PMID:24905583

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

    PubMed Central

    Padmanabhan, Laxmi Devi; Nampoothiri, Sheela

    2016-01-01

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

  5. Endotracheal Tube Management and Obstructed Airway.

    PubMed

    Sancheti, Manu; Force, Seth

    2015-08-01

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

  6. Tension chylothorax complicating acute malignant airway obstruction.

    PubMed

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

    2011-05-01

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

  7. [An almost fatal airway obstruction caused by a secretion plug in an endotracheal tube].

    PubMed

    Andersen, Emir Benjamin; Olsen, Karsten Skovgaard

    2014-12-15

    Airway obstruction caused by a secretion plug in an endotracheal tube or a tracheostomy cannula can be a serious complication to mechanical ventilation. This case describes an event caused by a mucus plug localized to the distal part of a tracheostomy tube in a tetraplegic patient. The plug functioned as a check valve, allowing air to pass in - but not out - of the patient. A suction catheter could be passed through the airway without any resistance, and thus the airway was believed to be free. The event, which had an almost fatal outcome due to hyperinflation of the lungs, was relieved by replacement of the tracheostomy cannula. PMID:25497629

  8. Luteolin Attenuates Airway Mucus Overproduction via Inhibition of the GABAergic System.

    PubMed

    Shen, Mei-Lin; Wang, Chen-Hung; Lin, Ching-Huei; Zhou, Ning; Kao, Shung-Te; Wu, Dong Chuan

    2016-01-01

    Airway mucus overproduction is one of the most common symptoms of asthma that causes severe clinical outcomes in patients. Despite the effectiveness of general asthma therapies, specific treatments that prevent mucus overproduction in asthma patients remain lacking. Recent studies have found that activation of GABAA receptors (GABAAR) is important for promoting mucus oversecretion in lung airway epithelia. Here, we report that luteolin, a natural flavonoid compound, suppresses mucus overproduction by functionally inhibiting the GABAergic system. This hypothesis was investigated by testing the effects of luteolin on goblet cell hyperplasia, excessive mucus secretion, and GABAergic transmission using histological and electrophysiological approaches. Our results showed that 10 mg/kg luteolin significantly decreased the number of goblet cells in the lung tissue and inhibited mucus overproduction in an in vivo asthma model induced by ovalbumin (OVA) in mice. Patch-clamp recordings showed that luteolin inhibited GABAAR-mediated currents in A549 cells. Furthermore, the inhibitory effects of luteolin on OVA-induced goblet cell hyperplasia and mucus overproduction were occluded by the GABAAR antagonist picrotoxin. In conclusion, our observations indicate that luteolin effectively attenuates mucus overproduction at least partially by inhibiting GABAARs, suggesting the potential for therapeutic administration of luteolin in the treatment of mucus overproduction in asthma patients. PMID:27595800

  9. Luteolin Attenuates Airway Mucus Overproduction via Inhibition of the GABAergic System

    PubMed Central

    Shen, Mei-Lin; Wang, Chen-Hung; Lin, Ching-Huei; Zhou, Ning; Kao, Shung-Te; Wu, Dong Chuan

    2016-01-01

    Airway mucus overproduction is one of the most common symptoms of asthma that causes severe clinical outcomes in patients. Despite the effectiveness of general asthma therapies, specific treatments that prevent mucus overproduction in asthma patients remain lacking. Recent studies have found that activation of GABAA receptors (GABAAR) is important for promoting mucus oversecretion in lung airway epithelia. Here, we report that luteolin, a natural flavonoid compound, suppresses mucus overproduction by functionally inhibiting the GABAergic system. This hypothesis was investigated by testing the effects of luteolin on goblet cell hyperplasia, excessive mucus secretion, and GABAergic transmission using histological and electrophysiological approaches. Our results showed that 10 mg/kg luteolin significantly decreased the number of goblet cells in the lung tissue and inhibited mucus overproduction in an in vivo asthma model induced by ovalbumin (OVA) in mice. Patch-clamp recordings showed that luteolin inhibited GABAAR-mediated currents in A549 cells. Furthermore, the inhibitory effects of luteolin on OVA-induced goblet cell hyperplasia and mucus overproduction were occluded by the GABAAR antagonist picrotoxin. In conclusion, our observations indicate that luteolin effectively attenuates mucus overproduction at least partially by inhibiting GABAARs, suggesting the potential for therapeutic administration of luteolin in the treatment of mucus overproduction in asthma patients. PMID:27595800

  10. Mechanisms of cilia-driven transport in the airways in the absence of mucus.

    PubMed

    Bermbach, Saskia; Weinhold, Karina; Roeder, Thomas; Petersen, Frank; Kugler, Christian; Goldmann, Torsten; Rupp, Jan; König, Peter

    2014-07-01

    Airway mucus is thought to be required for the clearance of inhaled particles by mucociliary transport, but this view has recently been challenged. To test if mucus is necessary for cilia-driven particle transport, we removed mucus from murine and human ex vivo airway preparations by thorough rinsing with buffer with or without additional dithiothreitol washing. The transport of particles with diameters of 4.5 μm, 200 nm, and 40 nm and of bacteria was analyzed by video microscopy. Complete removal of mucus was verified by wheat germ agglutinin staining and by scanning electron microscopy. In the absence of mucus, we observed efficient transport of particles and bacteria by direct cilia-mediated propulsion or via fluid flow generated by ciliary beating. Virus-sized particles had the tendency to attach to cilia. Because direct contact of particles with ciliated cells occurs in the absence of mucus, we examined if this direct interaction changes epithelial function. Neither bacteria- nor LPS-induced nuclear translocation of NF-κB p65 in ciliated cells occurred, indicating that mere contact between ciliated cells and bacteria during transport does not activate the epithelium. Attachment of virus-sized particles to cilia could induce mucus release and/or increase the ciliary beat frequency. Our results indicate that cilia-driven transport of particles with various sizes is possible in murine and human airways without the presence of mucus. If mucus-free transport fails, the epithelium can react by releasing mucus or increasing the ciliary beat frequency to maintain particle transport. PMID:24467665

  11. [Malocclusion and upper airway obstruction].

    PubMed

    Lopatiene, Kristina; Babarskas, Algis

    2002-01-01

    After more than a century of conjecture and heated argument, the orthodontic relevance of nasal obstruction and its assumed effect on facial growth continues to be debated. Oral respiration disrupts those muscle forces exerted by tongue, cheeks and lips upon the maxillary arch. The main characteristics of the respiratory obstruction syndrome are presence of hypertrophied tonsils or adenoids, mouth breathing, open-bite, cross-bite, excessive anterior face height, incompetent lip posture, excessive appearance of maxillary anterior teeth, narrow external nares, "V" shaped maxillary arch. The purpose of this study is to evaluate relationship between nasal obstruction and severity of malocclusion. The sample analyzed in this article consisted of 49 children aged from 7 to 15 years, who pronounced difficulty in breathing through the nose. Patients and their parents were interviewed, clinical examination was performed, and measurements from dental casts and panoramic radiograph were obtained. All patients were examined by otorhinolaryngologist, and the nasal obstruction was confirmed by posterior rhinomanometry test. This study showed the significant association between nasal resistance and increased overjet (p = 0.042), open bite (p = 0.033) and maxillary crowding (p = 0.037). The tendency of greater nasal resistance was observed for the patients with the first permanent molars relationship Angle II and posterior cross-bite. PMID:12474699

  12. Oxidation increases mucin polymer cross-links to stiffen airway mucus gels

    PubMed Central

    Yuan, Shaopeng; Hollinger, Martin; Lachowicz-Scroggins, Marrah E.; Kerr, Sheena C.; Dunican, Eleanor M.; Daniel, Brian M.; Ghosh, Sudakshina; Erzurum, Serpel C.; Willard, Belinda; Hazen, Stanley L.; Huang, Xiaozhu; Carrington, Stephen D.; Oscarson, Stefan; Fahy, John V.

    2015-01-01

    Airway mucus in cystic fibrosis (CF) is highly elastic, but the mechanism behind this pathology is unclear. We hypothesized that the biophysical properties of CF mucus are altered because of neutrophilic oxidative stress. Using confocal imaging, rheology, and biochemical measures of inflammation and oxidation, we found that CF airway mucus gels have a molecular architecture characterized by a core of mucin covered by a web of DNA and a rheological profile characterized by high elasticity that can be normalized by chemical reduction. We also found that high levels of reactive oxygen species in CF mucus correlated positively and significantly with high concentrations of the oxidized products of cysteine (disulfide cross-links). To directly determine whether oxidation can cross-link mucins to increase mucus elasticity, we exposed induced sputum from healthy subjects to oxidizing stimuli and found a marked and thiol-dependent increase in sputum elasticity. Targeting mucin disulfide cross-links using current thiol-amino structures such as N-acetylcysteine (NAC) requires high drug concentrations to have mucolytic effects. We therefore synthesized a thiol-carbohydrate structure (methyl 6-thio-6-deoxy-α-D-galactopyranoside) and found that it had stronger reducing activity than NAC and more potent and fast-acting mucolytic activity in CF sputum. Thus, oxidation arising from airway inflammation or environmental exposure contributes to pathologic mucus gel formation in the lung, which suggests that it can be targeted by thiol-modified carbohydrates. PMID:25717100

  13. Oxidation increases mucin polymer cross-links to stiffen airway mucus gels.

    PubMed

    Yuan, Shaopeng; Hollinger, Martin; Lachowicz-Scroggins, Marrah E; Kerr, Sheena C; Dunican, Eleanor M; Daniel, Brian M; Ghosh, Sudakshina; Erzurum, Serpel C; Willard, Belinda; Hazen, Stanley L; Huang, Xiaozhu; Carrington, Stephen D; Oscarson, Stefan; Fahy, John V

    2015-02-25

    Airway mucus in cystic fibrosis (CF) is highly elastic, but the mechanism behind this pathology is unclear. We hypothesized that the biophysical properties of CF mucus are altered because of neutrophilic oxidative stress. Using confocal imaging, rheology, and biochemical measures of inflammation and oxidation, we found that CF airway mucus gels have a molecular architecture characterized by a core of mucin covered by a web of DNA and a rheological profile characterized by high elasticity that can be normalized by chemical reduction. We also found that high levels of reactive oxygen species in CF mucus correlated positively and significantly with high concentrations of the oxidized products of cysteine (disulfide cross-links). To directly determine whether oxidation can cross-link mucins to increase mucus elasticity, we exposed induced sputum from healthy subjects to oxidizing stimuli and found a marked and thiol-dependent increase in sputum elasticity. Targeting mucin disulfide cross-links using current thiol-amino structures such as N-acetylcysteine (NAC) requires high drug concentrations to have mucolytic effects. We therefore synthesized a thiol-carbohydrate structure (methyl 6-thio-6-deoxy-α-D-galactopyranoside) and found that it had stronger reducing activity than NAC and more potent and fast-acting mucolytic activity in CF sputum. Thus, oxidation arising from airway inflammation or environmental exposure contributes to pathologic mucus gel formation in the lung, which suggests that it can be targeted by thiol-modified carbohydrates. PMID:25717100

  14. Heterogeneity of airways mucus: variations in the amounts and glycoforms of the major oligomeric mucins MUC5AC and MUC5B.

    PubMed Central

    Kirkham, Sara; Sheehan, John K; Knight, David; Richardson, Paul S; Thornton, David J

    2002-01-01

    Respiratory mucus contains a mixture of gel-forming mucins but the functional significance of these different mucin species is unknown. To help gain a better understanding of mucus in airways we therefore need to ascertain the concentration of each of the gel-forming mucins within respiratory secretions. Thus the aim of this study was to determine the amounts of specific gel-forming mucins directly from solubilized secretions of the airways and purified mucin preparations. We investigated the feasibility of using direct-binding ELISA employing mucin-specific antisera but were unable to obtain reliable data owing to interference with the immobilization of the mucins on the assay surface by 6 M urea and high levels of non-mucin proteins. We therefore developed an alternative approach based on quantitative Western blotting after agarose-gel electrophoresis, which was not subject to these problems. Here we demonstrate that this procedure provides reliable and reproducible data and have employed it to determine the amounts of the MUC2, MUC5AC and MUC5B mucins in saline-induced sputa from healthy airways and spontaneous sputa from asthmatic airways. Additionally we have used this procedure to analyse these glycoproteins in mucin preparations purified from cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) mucus. Our findings indicate that MUC5AC and MUC5B are the major oligomeric mucins and that airways mucus contains variable amounts of these glycoproteins. By contrast, the MUC2 mucin comprised, at most, only 2.5% of the weight of the gel-forming mucins, indicating that MUC2 is a minor component in sputum. Finally, we show that the amounts and glycosylated variants of the MUC5AC and MUC5B mucins can be altered significantly in diseased airways with, for instance, an increase in the low-charge form of the MUC5B mucin in CF and COPD mucus. PMID:11802783

  15. Airway obstruction by an unexpected equipment damage.

    PubMed

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

    2016-08-01

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

  16. A microfluidic model to study fluid dynamics of mucus plug rupture in small lung airways

    PubMed Central

    Hu, Yingying; Bian, Shiyao; Grotberg, John; Filoche, Marcel; White, Joshua; Takayama, Shuichi; Grotberg, James B.

    2015-01-01

    Fluid dynamics of mucus plug rupture is important to understand mucus clearance in lung airways and potential effects of mucus plug rupture on epithelial cells at lung airway walls. We established a microfluidic model to study mucus plug rupture in a collapsed airway of the 12th generation. Mucus plugs were simulated using Carbopol 940 (C940) gels at concentrations of 0.15%, 0.2%, 0.25%, and 0.3%, which have non-Newtonian properties close to healthy and diseased lung mucus. The airway was modeled with a polydimethylsiloxane microfluidic channel. Plug motion was driven by pressurized air. Global strain rates and shear stress were defined to quantitatively describe plug deformation and rupture. Results show that a plug needs to overcome yield stress before deformation and rupture. The plug takes relatively long time to yield at the high Bingham number. Plug length shortening is the more significant deformation than shearing at gel concentration higher than 0.15%. Although strain rates increase dramatically at rupture, the transient shear stress drops due to the shear-thinning effect of the C940 gels. Dimensionless time-averaged shear stress, Txy, linearly increases from 3.7 to 5.6 times the Bingham number as the Bingham number varies from 0.018 to 0.1. The dimensionless time-averaged shear rate simply equals to Txy/2. In dimension, shear stress magnitude is about one order lower than the pressure drop, and one order higher than yield stress. Mucus with high yield stress leads to high shear stress, and therefore would be more likely to cause epithelial cell damage. Crackling sounds produced with plug rupture might be more detectable for gels with higher concentration. PMID:26392827

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

    PubMed Central

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

    2008-01-01

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

  18. Therapeutic Bronchoscopy for Malignant Central Airway Obstruction

    PubMed Central

    Ernst, Armin; Grosu, Horiana B.; Lei, Xiudong; Diaz-Mendoza, Javier; Slade, Mark; Gildea, Thomas R.; Machuzak, Michael S.; Jimenez, Carlos A.; Toth, Jennifer; Kovitz, Kevin L.; Ray, Cynthia; Greenhill, Sara; Casal, Roberto F.; Almeida, Francisco A.; Wahidi, Momen M.; Eapen, George A.; Feller-Kopman, David; Morice, Rodolfo C.; Benzaquen, Sadia; Tremblay, Alain; Simoff, Michael; Kovitz, Kevin; Greenhill, Sara; Gildea, Thomas R.; Machuzak, Michael; Almeida, Francisco A.; Cicenia, Joseph; Wahidi, Momen; Mahmood, Kamran; MacEachern, Paul; Tremblay, Alain; Simoff, Michael; Diaz-Mendoza, Javier; Ray, Cynthia; Feller-Kopman, David; Yarmus, Lonny; Estrada-Y-Martin, Rosa; Casal, Roberto F.; Toth, Jennifer; Karunakara, Raj; Slade, Mark; Ernst, Armin; Rafeq, Samaan; Ost, David; Eapen, George A.; Jimenez, Carlos A.; Morice, Rodolfo C.; Benzaquen, Sadia; Puchalski, Jonathan

    2015-01-01

    BACKGROUND: There is significant variation between physicians in terms of how they perform therapeutic bronchoscopy, but there are few data on whether these differences impact effectiveness. METHODS: This was a multicenter registry study of patients undergoing therapeutic bronchoscopy for malignant central airway obstruction. The primary outcome was technical success, defined as reopening the airway lumen to > 50% of normal. Secondary outcomes were dyspnea as measured by the Borg score and health-related quality of life (HRQOL) as measured by the SF-6D. RESULTS: Fifteen centers performed 1,115 procedures on 947 patients. Technical success was achieved in 93% of procedures. Center success rates ranged from 90% to 98% (P = .02). Endobronchial obstruction and stent placement were associated with success, whereas American Society of Anesthesiology (ASA) score > 3, renal failure, primary lung cancer, left mainstem disease, and tracheoesophageal fistula were associated with failure. Clinically significant improvements in dyspnea occurred in 90 of 187 patients measured (48%). Greater baseline dyspnea was associated with greater improvements in dyspnea, whereas smoking, having multiple cancers, and lobar obstruction were associated with smaller improvements. Clinically significant improvements in HRQOL occurred in 76 of 183 patients measured (42%). Greater baseline dyspnea was associated with greater improvements in HRQOL, and lobar obstruction was associated with smaller improvements. CONCLUSIONS: Technical success rates were high overall, with the highest success rates associated with stent placement and endobronchial obstruction. Therapeutic bronchoscopy should not be withheld from patients based solely on an assessment of risk, since patients with the most dyspnea and lowest functional status benefitted the most. PMID:25358019

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

    PubMed

    Zapletal, A; Zbojan, J; Pohanka, V

    1992-03-01

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

  20. Airway obstruction among Latino poultry processing workers in North Carolina.

    PubMed

    Mirabelli, Maria C; Chatterjee, Arjun B; Mora, Dana C; Arcury, Thomas A; Blocker, Jill N; Chen, Haiying; Grzywacz, Joseph G; Marín, Antonio J; Schulz, Mark R; Quandt, Sara A

    2015-01-01

    This analysis was conducted to evaluate the prevalence of airway obstruction among Latino poultry processing workers. Data were collected from 279 poultry processing workers and 222 other manual laborers via spirometry and interviewer-administered questionnaires. Participants employed in poultry processing reported the activities they perform at work. Participants with forced expiratory volume in 1 second (FEV1) or FEV1/forced expiratory volume (FVC) below the lower limits of normal were categorized as having airway obstruction. Airway obstruction was identified in 13% of poultry processing workers and 12% of the comparison population. Among poultry processing workers, the highest prevalence of airway obstruction (21%) occurred among workers deboning chickens (prevalence ratio: 1.75; 95% confidence interval: 0.97, 3.15). These findings identify variations in the prevalence of airway obstruction across categories of work activities. PMID:24965321

  1. Fourteen cases of imposed upper airway obstruction.

    PubMed Central

    Samuels, M P; McClaughlin, W; Jacobson, R R; Poets, C F; Southall, D P

    1992-01-01

    Imposed upper airway obstruction was diagnosed as the cause of recurrent and severe cyanotic episodes in 14 patients. Episodes started between 0.8 and 33 months of age (median 1.4) and occurred over a period of 0.8 to 20 months (median 3.5). Diagnosis was made by covert video surveillance, instituted after either (a) the observation that episodes began only in the presence of one person, or (b) characteristic findings on physiological recordings, lasting between 12 hours and three weeks, performed in hospital or at home. Surveillance was undertaken for between 15 minutes and 12 days (median 24 hours) and resulted in safety for the patient and psychiatric assessment of the parent: mother (n = 12), father (n = 1), and grandmother (n = 1). These revealed histories of sexual, physical, or emotional abuse (n = 11), self harm (n = 9), factitious illness (n = 7), eating disorder (n = 10), and previous involvement with a psychiatrist (n = 7). Management of the abusing parents is complex, but recognition of their psychosocial characteristics may allow earlier diagnosis. Imposed upper airway obstruction should be considered and excluded by physiological recordings in any infant or young child with recurrent cyanotic episodes. If physiological recordings fail to substantiate a natural cause for episodes, covert video surveillance may be essential to protect the child from further injury or death. PMID:1543373

  2. Computed tomography of nonanesthetized cats with upper airway obstruction.

    PubMed

    Stadler, Krystina; O'Brien, Robert

    2013-01-01

    Upper airway obstruction is a potentially life-threatening problem in cats and for which a noninvasive, sensitive method rapid diagnosis is needed. The purposes of this prospective study were to describe a computed tomography (CT) technique for nonanesthetized cats with upper airway obstruction, CT characteristics of obstructive diseases, and comparisons between CT findings and findings from other diagnostic tests. Ten cats with clinical signs of upper airway obstruction were recruited for the study. Four cats with no clinical signs of upper airway obstruction were recruited as controls. All cats underwent computed tomography imaging without sedation or anesthesia, using a 16-slice helical CT scanner and a previously described transparent positional device. Three-dimensional (3D) internal volume rendering was performed on all CT image sets and 3D external volume rendering was also performed on cats with evidence of mass lesions. Confirmation of upper airway obstruction was based on visual laryngeal examination, endoscopy, fine-needle aspirate, biopsy, or necropsy. Seven cats were diagnosed with intramural upper airway masses, two with laryngotracheitis, and one with laryngeal paralysis. The CT and 3D volume-rendered images identified lesions consistent with upper airway disease in all cats. In cats with mass lesions, CT accurately identified the mass and location. Findings from this study supported the use of CT imaging as an effective technique for diagnosing upper airway obstruction in nonanesthetized cats. PMID:23441677

  3. Proteomic Analysis of Pure Human Airway Gland Mucus Reveals a Large Component of Protective Proteins

    PubMed Central

    Joo, Nam Soo; Evans, Idil Apak T.; Cho, Hyung-Ju; Park, Il-Ho; Engelhardt, John F.; Wine, Jeffrey J.

    2015-01-01

    Airway submucosal glands contribute to innate immunity and protect the lungs by secreting mucus, which is required for mucociliary clearance and which also contains antimicrobial, anti-inflammatory, anti-proteolytic and anti-oxidant proteins. We stimulated glands in tracheal trimmings from three lung donors and collected droplets of uncontaminated mucus as they formed at the gland orifices under an oil layer. We analyzed the mucus using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Analysis identified 5486 peptides and 441 proteins from across the 3 samples (269–319 proteins per subject). We focused on 269 proteins common to at least 2 0f 3 subjects, of which 102 (38%) had protective or innate immunity functions. While many of these have long been known to play such roles, for many others their cellular protective functions have only recently been appreciated in addition to their well-studied biologic functions (e.g. annexins, apolipoproteins, gelsolin, hemoglobin, histones, keratins, and lumican). A minority of the identified proteins are known to be secreted via conventional exocytosis, suggesting that glandular secretion occurs via multiple mechanisms. Two of the observed protective proteins, major vault protein and prohibitin, have not been observed in fluid from human epithelial cultures or in fluid from nasal or bronchoalveolar lavage. Further proteomic analysis of pure gland mucus may help clarify how healthy airways maintain a sterile environment. PMID:25706550

  4. Airway obstruction secondary to large thyroid adenolipoma

    PubMed Central

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

    2014-01-01

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

  5. Laryngeal amyloidosis causing hoarseness and airway obstruction.

    PubMed

    Gallivan, Gregory J; Gallivan, Helen K

    2010-03-01

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

  6. Partial airway obstruction following manufacturing defect in laryngeal mask airway (Laryngeal Mask Silken™).

    PubMed

    Jangra, Kiran; Malhotra, Surender Kumar; Saini, Vikas

    2014-10-01

    Laryngeal mask (LM) airway is commonly used for securing airway in day-care surgeries. Various problems have been described while using LM airway. Out of those, mechanical obstruction causing airway compromise is most common. Here, we describe a case report of 4-year-old child who had partial upper airway obstruction due to LM manufacturer's defect. There was a silicon band in upper one-third of shaft of LM airway. This band was made up of the same material as that of LM airway so it was not identifiable on external inspection of transparent shaft. We suggest that such as non-transparent laryngeal mask, a transparent LM airway should also be inspected looking inside the lumen with naked eyes or by using a probe to rule out any manufacturing defect before its insertion. PMID:25422617

  7. Effect of epithelium ATP release on cyclic pressure-induced airway mucus secretion

    PubMed Central

    Tong, Jin; Zhou, Xiang-dong; Perelman, Juliy M.; Kolosov, Victor P.

    2013-01-01

    The cyclic mechanical effect of airflow during breathing creates the optimal airway hydration state. MUC (mucin) 5AC is an important component of the airway mucus. The formation of MUC5AC is related to ATP and intracellular calcium in the epithelial cells. In this study, we evaluated the effect of ATP release from intracellular calcium in epithelial cells on cyclic pressure-induced mucus secretion in the airway. 16HBE (human bronchial epithelial cells) were cultured in vitro on cyclically tilted cultured plates and divided into five groups: control, tilt, tilt and BAPTA–AM (1,2-bis-(o-aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid–acetoxymethyl ester), tilt and EGTA and tilt and RB-2 (reactive blue-2). The shear stress and compressive stress were induced by the surface tension of the liquid, atmospheric pressure and liquid gravity. Cell activity, MUC5AC mRNA expression level, MUC5AC protein expression level and ATP release and intracellular calcium changes were measured with the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) assay, RT–PCR (reverse transcription–PCR), HPLC and inverted fluorescence microscope, respectively. We detected that cyclic pressure significantly increased MUC5AC secretion and ATP release. The enhanced ATP release could be inhibited by both BAPTA–AM and RB-2, while EGTA did not have a suppressive effect. BAPTA–AM, EGTA and RB-2 did not obviously inhibit MUC5AC mRNA expression. Cyclic pressure did not induce MUC5AC secretion in the airway mucus epithelium via Ca2+-dependent ATP release, and nearly all Ca2+ was provided by stored intracellular Ca2+. PMID:24329423

  8. Effect of epithelium ATP release on cyclic pressure-induced airway mucus secretion.

    PubMed

    Tong, Jin; Zhou, Xiang-Dong; Perelman, Juliy M; Kolosov, Victor P

    2013-12-16

    The cyclic mechanical effect of airflow during breathing creates the optimal airway hydration state. Mucin (MUC) 5AC is an impotent component of the airway mucus. The formation of MUC5AC is related to adenosine triphosphate (ATP) and intracellular calciumin the epithelial cells. In this study, we evaluated the effect of ATP release from and intracellular calcium in epithelial cells on cyclic pressure-induced mucus secretion in the airway. Human bronchial epithelial cells (16HBE) were cultured in vitro on cyclically tilted cultured plates and divided into 5 groups: control, tilt, tilt and BAPTA-AM, tilt and EGTA, and tilt and RB-2. The shear stress and compressive stress were induced by the surface tension of the liquid, atmospheric pressure and liquid gravity. Cell activity, MUC5AC mRNA expression level, MUC5AC protein expression level and ATP release, and intracellular calcium changes were measured with the MTT assay, RT-PCR, high performance liquid chromatography (HPLC) and inverted fluorescence microscope, respectively. We detected that cyclic pressure significantly increased MUC5AC secretion and ATP release. The enhanced ATP release could be inhibited by both BAPTA-AM and RB-2, while EGTA did not have a suppressive effect. BAPTA-AM, EGTA, and RB-2 did not obviously inhibit MUC5AC mRNA expression.Cyclic pressure did not induce MUC5AC secretion in the airway mucus epithelium via Ca2+-dependent ATP release, and nearly all Ca2+ was provided by stored intracellular Ca2+. PMID:24329423

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

    NASA Astrophysics Data System (ADS)

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

    2016-03-01

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

  10. Viscous airflow through a rigid tube with a compliant lining: a simple model for the air-mucus interaction in pulmonary airways.

    PubMed

    Evrensel, C A; Khan, R U; Elli, S; Krumpe, P E

    1993-08-01

    The respiratory tract of mammals is lined with a layer of mucus, described as viscoelastic semi-solid, above a layer of watery serous fluid. The interaction of these compliant layers with pulmonary airflow plays a major role in lung clearance by two-phase gas-liquid flow and in increased flow resistance in patients with obstructive airway diseases such as cystic fibrosis, chronic bronchitis and asthma. Experiments have shown that such coupled systems of flow-compliant-layers are quite susceptible to sudden shear instabilities, leading to formation of relatively large amplitude waves at the interface. Although these waves enhance the lung clearance by mobilizing the secretions, they increase the flow resistance in airways. The objective of this paper is to understand the basic interaction mechanism between the two media better by studying airflow through a rigid pipe that is lined by a compliant layer. The mathematical model that has been developed for this purpose is capable of explaining some of the published experimental observations. Wave instability theory is applied to the coupled air-mucus system to explore the stability of the interface. The results show that the onset flow speed for the initiation of unstable surface waves, and the resulting wavelength, are both very sensitive to mucus thickness. The model predicts that the instabilities initiate in the form of propagating waves for the elastic mucus where the wave speed is about 40 percent of the flow speed. The wavelength and phase speed to air velocity ratio are shown to increase with increasing mucus thickness.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8231141

  11. A crucial role of Flagellin in the induction of airway mucus production by Pseudomonas aeruginosa.

    PubMed

    Ben Mohamed, Fatima; Mohamed, Fatima Ben; Garcia-Verdugo, Ignacio; Medina, Mathieu; Balloy, Viviane; Chignard, Michel; Ramphal, Reuben; Touqui, Lhousseine

    2012-01-01

    Pseudomonas aeruginosa is an opportunistic pathogen involved in nosocomial infections. Flagellin is a P. aeruginosa virulence factor involved in host response to this pathogen. We examined the role of flagellin in P. aeruginosa-induced mucus secretion. Using a mouse model of pulmonary infection we showed that PAK, a wild type strain of P. aeruginosa, induced airway mucus secretion and mucin muc5ac expression at higher levels than its flagellin-deficient mutant (ΔFliC). PAK induced expression of MUC5AC and MUC2 in both human airway epithelial NCI-H292 cell line and in primary epithelial cells. In contrast, ΔFliC infection had lower to no effect on MUC5AC and MUC2 expressions. A purified P. aeruginosa flagellin induced MUC5AC expression in parallel to IL-8 secretion in NCI-H292 cells. Accordingly, ΔFliC mutant stimulated IL-8 secretion at significantly lower levels compared to PAK. Incubation of NCI-H292 cells with exogenous IL-8 induced MUC5AC expression and pre-incubation of these cells with an anti-IL-8 antibody abrogated flagellin-mediated MUC5AC expression. Silencing of TLR5 and Naip, siRNA inhibited both flagellin-induced MUC5AC expression and IL-8 secretion. Finally, inhibition of ERK abolished the expression of both PAK- and flagellin-induced MUC5AC. We conclude that: (i) flagellin is crucial in P. aeruginosa-induced mucus hyper-secretion through TLR5 and Naip pathways; (ii) this process is mediated by ERK and amplified by IL-8. Our findings help understand the mechanisms involved in mucus secretion during pulmonary infectious disease induced by P. aeruginosa, such as in cystic fibrosis. PMID:22768318

  12. Altered Sputum Microstructure as a Marker of Airway Obstruction in Cystic Fibrosis Patients

    NASA Astrophysics Data System (ADS)

    Duncan, Gregg; Jung, James; West, Natalie; Boyle, Michael; Suk, Jung Soo; Hanes, Justin

    In the lungs of cystic fibrosis (CF) patients, highly viscoelastic mucus remains stagnant in the lung leading to obstructed airways prone to recurrent infections. Bulk-fluid rheological measurement is primarily used to assess the pathological features of mucus. However, this approach is limited in detecting microscopic properties on the length scale of pathogens and immune cells. We have shown in prior work based on the transport of muco-inert nanoparticles (MIP) in CF sputum that patients can carry significantly different microstructural properties. In this study, we aimed to determine the factors leading to variations between patients in sputum microstructure and their clinical implications. The microrheological properties of CF sputum were measured using multi-particle tracking experiments of MIP. MIP were made by grafting polyethylene glycol onto the surface of polystyrene nanoparticles which prior work has shown prevents adhesion to CF sputum. Biochemical analyses show that sputum microstructure was significantly altered by elevated mucin and DNA content. Reduction in sputum pore size is characteristic of patients with obstructed airways as indicated by measured pulmonary function tests. Our microstructural read-out may serve as a novel biomarker for CF.

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

    PubMed Central

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

    2015-01-01

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

  14. Analysis of airway secretions in a model of sulfur dioxide induced chronic obstructive pulmonary disease (COPD)

    PubMed Central

    Wagner, Ulrich; Staats, Petra; Fehmann, Hans-Christoph; Fischer, Axel; Welte, Tobias; Groneberg, David A

    2006-01-01

    Hypersecretion and chronic phlegm are major symptoms of chronic obstructive pulmonary disease (COPD) but animal models of COPD with a defined functional hypersecretion have not been established so far. To identify an animal model of combined morphological signs of airway inflammation and functional hypersecretion, rats were continuously exposed to different levels of sulfur dioxide (SO2, 5 ppm, 10 ppm, 20 ppm, 40 ppm, 80 ppm) for 3 (short-term) or 20–25 (long-term) days. Histology revealed a dose-dependent increase in edema formation and inflammatory cell infiltration in short-term-exposed animals. The submucosal edema was replaced by fibrosis after long-term-exposure. The basal secretory activity was only significantly increased in the 20 ppm group. Also, stimulated secretion was significantly increased only after exposure to 20 ppm. BrdU-assays and AgNOR-analysis demonstrated cellular metaplasia and glandular hypertrophy rather than hyperplasia as the underlying morphological correlate of the hypersecretion. In summary, SO2-exposure can lead to characteristic airway remodeling and changes in mucus secretion in rats. As only long-term exposure to 20 ppm leads to a combination of hypersecretion and airway inflammation, only this mode of exposure should be used to mimic human COPD. Concentrations less or higher than 20 ppm or short term exposure do not induce the respiratory symptom of hypersecretion. The present model may be used to characterize the effects of new compounds on mucus secretion in the background of experimental COPD. PMID:16759388

  15. [Acute airway obstruction during chemotherapy-induced agranulocytosis with fever].

    PubMed

    Vandenbos, F; Deswardt, Ph; Hyvernat, H; Burel-Vandenbos, F; Bernardin, G

    2006-02-01

    Acute airway obstruction caused by mucoid impaction can cause sometimes life-threatening respiratory distress. Bronchial plugging is usually observed in subjects with chronic diseases such as asthma, allergic bronchopulmonary aspergillosis, or cystic fibrosis. In children, it can be related to heart failure. Acute airway obstruction in a patient without a chronic respiratory disease is exceptional. We report the case of a patient who developed bronchial plugs obstructing the bronchi during a period of agranulocytosis induced by chemotherapy. The patient experienced acute respiratory distress with asphyxia. The plugs were composed of fibrin and required several fibroscopic procedures for clearance. To our knowledge, this is the first case report of acute airway obstruction by plugging during a period of agranulocytosis. PMID:16604039

  16. Imaging of mucus clearance in the airways of living spontaneously breathing mice by optical coherence microscopy (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Pieper, Mario; Schulz-Hildebrandt, Hinnerk; Hüttmann, Gereon; König, Peter

    2016-03-01

    Mucus transport is essential to remove inhaled particles and pathogens from the lung. Impaired removal of mucus often results in worsening of lung diseases. To understand the mechanisms of mucus transport and to monitor the impact of therapeutic strategies, it is essential to visualize airways and mucus in living animals without disturbing transport processes by intubation or surgically opening the airways. We developed a custom-built optical coherence microscope (OCM) providing a lateral and axial resolution of approximately 1.5 µm with a field of view of 2 mm at up to 150 images/s. Images of the intact trachea and its mucus transport were recorded in anesthetized spontaneously breathing mice. NaCl solution (0.9% and 7%) or Lipopolysaccharide were applied intranasally. OCM resolved detailed structure of the trachea and enabled measuring the airway surface liquid (ASL) thickness through the tracheal wall. Without stimulation, the amount of ASL was only a few µm above the epithelium and remained constant. After intranasal application of 30 µl saline at different concentrations, an early fast cough-like fluid removal with velocities higher than 1 mm/s was observed that removed a high amount of liquid. The ASL thickness increased transiently and quickly returned to levels before stimulation. In contrast to saline, application of Lipopolysaccharide induced substantial mucus release and an additional slow mucus transport by ciliary beating (around 100 µm/s) towards the larynx was observed. In conclusion, OCM is appropriate unique tool to study mechanisms of mucus transport in the airways and effects of therapeutic interventions in living animals.

  17. Cold-inducible RNA-binding protein mediates airway inflammation and mucus hypersecretion through a post-transcriptional regulatory mechanism under cold stress.

    PubMed

    Juan, Yang; Haiqiao, Wu; Xie, Wenyao; Huaping, Huang; Zhong, Han; Xiangdong, Zhou; Kolosov, Victor P; Perelman, Juliy M

    2016-09-01

    Acute or chronic cold exposure exacerbates chronic inflammatory airway diseases, such as chronic obstructive pulmonary disease (COPD) and asthma. Cold-inducible RNA-binding protein (CIRP) is a cold-shock protein and is induced by various environmental stressors, such as hypothermia and hypoxia. In this study, we showed that CIRP gene and protein levels were significantly increased in patients with COPD and in rats with chronic airway inflammation compared with healthy subjects. Similarly, inflammatory cytokine production and MUC5AC secretion were up-regulated in rats following cigarette smoke inhalation. Cold temperature-induced CIRP overexpression and translocation were shown to be dependent on arginine methylation in vitro. CIRP overexpression promoted stress granule (SG) assembly. In the cytoplasm, the stability of pro-inflammatory cytokine mRNAs was increased through specific interactions between CIRP and mediator mRNA 3'-UTRs; these interactions increased the mRNA translation, resulting in MUC5AC overproduction in response to cold stress. Conversely, CIRP silencing and a methyltransferase inhibitor (adenosine dialdehyde) promoted cytokine mRNA degradation and inhibited the inflammatory response and mucus hypersecretion. These findings indicate that cold temperature can induce an airway inflammatory response and excess mucus production via a CIRP-mediated increase in mRNA stability and protein translation. PMID:27477308

  18. Copper oxide nanoparticles aggravate airway inflammation and mucus production in asthmatic mice via MAPK signaling.

    PubMed

    Park, Ji-Won; Lee, In-Chul; Shin, Na-Rae; Jeon, Chan-Mi; Kwon, Ok-Kyoung; Ko, Je-Won; Kim, Jong-Choon; Oh, Sei-Ryang; Shin, In-Sik; Ahn, Kyung-Seop

    2016-05-01

    Copper oxide nanoparticles (CuONPs), metal oxide nanoparticles were used in multiple applications including wood preservation, antimicrobial textiles, catalysts for carbon monoxide oxidation and heat transfer fluid in machines. We investigated the effects of CuONPs on the respiratory system in Balb/c mice. In addition, to investigate the effects of CuONPs on asthma development, we used a murine model of ovalbumin (OVA)-induced asthma. CuONPs markedly increased airway hyper-responsiveness (AHR), inflammatory cell counts, proinflammatory cytokines and reactive oxygen species (ROS). CuONPs induced airway inflammation and mucus secretion with increases in phosphorylation of the MAPKs (Erk, JNK and p38). In the OVA-induced asthma model, CuONPs aggravated the increased AHR, inflammatory cell count, proinflammatory cytokines, ROS and immunoglobulin E induced by OVA exposure. In addition, CuONPs markedly increased inflammatory cell infiltration into the lung and mucus secretions, and MAPK phosphorylation was elevated compared to OVA-induced asthmatic mice. Taken together, CuONPs exhibited toxicity on the respiratory system, which was associated with the MAPK phosphorylation. In addition, CuONPs exposure aggravated the development of asthma. We conclude that CuONPs exposure has a potential toxicity in humans with respiratory disease. PMID:26472121

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

    PubMed Central

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

    2007-01-01

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

  20. Clinical issues of mucus accumulation in COPD

    PubMed Central

    Ramos, Frederick L; Krahnke, Jason S; Kim, Victor

    2014-01-01

    Airway mucus is part of the lung’s native immune function that traps particulates and microorganisms, enabling their clearance from the lung by ciliary transport and cough. Mucus hypersecretion and chronic productive cough are the features of the chronic bronchitis and chronic obstructive pulmonary disease (COPD). Overproduction and hypersecretion by goblet cells and the decreased elimination of mucus are the primary mechanisms responsible for excessive mucus in chronic bronchitis. Mucus accumulation in COPD patients affects several important outcomes such as lung function, health-related quality of life, COPD exacerbations, hospitalizations, and mortality. Nonpharmacologic options for the treatment of mucus accumulation in COPD are smoking cessation and physical measures used to promote mucus clearance. Pharmacologic therapies include expectorants, mucolytics, methylxanthines, beta-adrenergic receptor agonists, anticholinergics, glucocorticoids, phosphodiesterase-4 inhibitors, antioxidants, and antibiotics. PMID:24493923

  1. Within-breath respiratory impedance and airway obstruction in patients with chronic obstructive pulmonary disease

    PubMed Central

    da Silva, Karla Kristine Dames; Faria, Alvaro Camilo Dias; Lopes, Agnaldo José; de Melo, Pedro Lopes

    2015-01-01

    OBJECTIVE: Recent work has suggested that within-breath respiratory impedance measurements performed using the forced oscillation technique may help to noninvasively evaluate respiratory mechanics. We investigated the influence of airway obstruction on the within-breath forced oscillation technique in smokers and chronic obstructive pulmonary disease patients and evaluated the contribution of this analysis to the diagnosis of chronic obstructive pulmonary disease. METHODS: Twenty healthy individuals and 20 smokers were assessed. The study also included 74 patients with stable chronic obstructive pulmonary disease. We evaluated the mean respiratory impedance (Zm) as well as values for the inspiration (Zi) and expiration cycles (Ze) at the beginning of inspiration (Zbi) and expiration (Zbe), respectively. The peak-to-peak impedance (Zpp=Zbe-Zbi) and the respiratory cycle dependence (ΔZrs=Ze-Zi) were also analyzed. The diagnostic utility was evaluated by investigating the sensitivity, the specificity and the area under the receiver operating characteristic curve. ClinicalTrials.gov: NCT01888705. RESULTS: Airway obstruction increased the within-breath respiratory impedance parameters that were significantly correlated with the spirometric indices of airway obstruction (R=−0.65, p<0.0001). In contrast to the control subjects and the smokers, the chronic obstructive pulmonary disease patients presented significant expiratory-inspiratory differences (p<0.002). The adverse effects of moderate airway obstruction were detected based on the Zpp with an accuracy of 83%. Additionally, abnormal effects in severe and very severe patients were detected based on the Zm, Zi, Ze, Zbe, Zpp and ΔZrs with a high degree of accuracy (>90%). CONCLUSIONS: We conclude the following: (1) chronic obstructive pulmonary disease introduces higher respiratory cycle dependence, (2) this increase is proportional to airway obstruction, and (3) the within-breath forced oscillation technique may

  2. Malignant Extra Renal Rhabdoid Tumour Presenting as Central Airway Obstruction

    PubMed Central

    Bal, Amanjit; Agarwal, Ritesh; Das, Ashim

    2014-01-01

    Rhabdoid tumours are one of the most aggressive childhood neoplasms associated with high mortality. The commonest age group affected is children less than five years of age. Rhabdoid tumour presenting as an endoluminal tracheal mass leading to central airway obstruction has not been previously reported. We describe the case of a 17-year-old male patient where malignant rhabdoid tumour masqueraded as bronchial asthma leading to a delayed diagnosis of upper airway obstruction by tracheal growth. Histopathological examination and immunohistochemistry confirmed the diagnosis of malignant rhabdoid tumour. PMID:25243090

  3. In vivo imaging of airway cilia and mucus clearance with micro-optical coherence tomography

    PubMed Central

    Chu, Kengyeh K.; Unglert, Carolin; Ford, Tim N.; Cui, Dongyao; Carruth, Robert W.; Singh, Kanwarpal; Liu, Linbo; Birket, Susan E.; Solomon, George M.; Rowe, Steven M.; Tearney, Guillermo J.

    2016-01-01

    We have designed and fabricated a 4 mm diameter rigid endoscopic probe to obtain high resolution micro-optical coherence tomography (µOCT) images from the tracheal epithelium of living swine. Our common-path fiber-optic probe used gradient-index focusing optics, a selectively coated prism reflector to implement a circular-obscuration apodization for depth-of-focus enhancement, and a common-path reference arm and an ultra-broadbrand supercontinuum laser to achieve high axial resolution. Benchtop characterization demonstrated lateral and axial resolutions of 3.4 μm and 1.7 μm, respectively (in tissue). Mechanical standoff rails flanking the imaging window allowed the epithelial surface to be maintained in focus without disrupting mucus flow. During in vivo imaging, relative motion was mitigated by inflating an airway balloon to hold the standoff rails on the epithelium. Software implemented image stabilization was also implemented during post-processing. The resulting image sequences yielded co-registered quantitative outputs of airway surface liquid and periciliary liquid layer thicknesses, ciliary beat frequency, and mucociliary transport rate, metrics that directly indicate airway epithelial function that have dominated in vitro research in diseases such as cystic fibrosis, but have not been available in vivo. PMID:27446685

  4. A novel siderophore system is essential for the growth of Pseudomonas aeruginosa in airway mucus.

    PubMed

    Gi, Mia; Lee, Kang-Mu; Kim, Sang Cheol; Yoon, Joo-Heon; Yoon, Sang Sun; Choi, Jae Young

    2015-01-01

    Pseudomonas aeruginosa establishes airway infections in Cystic Fibrosis patients. Here, we investigate the molecular interactions between P. aeruginosa and airway mucus secretions (AMS) derived from the primary cultures of normal human tracheal epithelial (NHTE) cells. PAO1, a prototype strain of P. aeruginosa, was capable of proliferating during incubation with AMS, while all other tested bacterial species perished. A PAO1 mutant lacking PA4834 gene became susceptible to AMS treatment. The ΔPA4834 mutant was grown in AMS supplemented with 100 μM ferric iron, suggesting that the PA4834 gene product is involved in iron metabolism. Consistently, intracellular iron content was decreased in the mutant, but not in PAO1 after the AMS treatment. Importantly, a PAO1 mutant unable to produce both pyoverdine and pyochelin remained viable, suggesting that these two major siderophore molecules are dispensable for maintaining viability during incubation with AMS. The ΔPA4834 mutant was regrown in AMS amended with 100 μM nicotianamine, a phytosiderophore whose production is predicted to be mediated by the PA4836 gene. Infectivity of the ΔPA4834 mutant was also significantly compromised in vivo. Together, our results identify a genetic element encoding a novel iron acquisition system that plays a previously undiscovered role in P. aeruginosa airway infection. PMID:26446565

  5. A novel siderophore system is essential for the growth of Pseudomonas aeruginosa in airway mucus

    PubMed Central

    Gi, Mia; Lee, Kang-Mu; Kim, Sang Cheol; Yoon, Joo-Heon; Yoon, Sang Sun; Choi, Jae Young

    2015-01-01

    Pseudomonas aeruginosa establishes airway infections in Cystic Fibrosis patients. Here, we investigate the molecular interactions between P. aeruginosa and airway mucus secretions (AMS) derived from the primary cultures of normal human tracheal epithelial (NHTE) cells. PAO1, a prototype strain of P. aeruginosa, was capable of proliferating during incubation with AMS, while all other tested bacterial species perished. A PAO1 mutant lacking PA4834 gene became susceptible to AMS treatment. The ΔPA4834 mutant was grown in AMS supplemented with 100 μM ferric iron, suggesting that the PA4834 gene product is involved in iron metabolism. Consistently, intracellular iron content was decreased in the mutant, but not in PAO1 after the AMS treatment. Importantly, a PAO1 mutant unable to produce both pyoverdine and pyochelin remained viable, suggesting that these two major siderophore molecules are dispensable for maintaining viability during incubation with AMS. The ΔPA4834 mutant was regrown in AMS amended with 100 μM nicotianamine, a phytosiderophore whose production is predicted to be mediated by the PA4836 gene. Infectivity of the ΔPA4834 mutant was also significantly compromised in vivo. Together, our results identify a genetic element encoding a novel iron acquisition system that plays a previously undiscovered role in P. aeruginosa airway infection. PMID:26446565

  6. In vivo imaging of airway cilia and mucus clearance with micro-optical coherence tomography.

    PubMed

    Chu, Kengyeh K; Unglert, Carolin; Ford, Tim N; Cui, Dongyao; Carruth, Robert W; Singh, Kanwarpal; Liu, Linbo; Birket, Susan E; Solomon, George M; Rowe, Steven M; Tearney, Guillermo J

    2016-07-01

    We have designed and fabricated a 4 mm diameter rigid endoscopic probe to obtain high resolution micro-optical coherence tomography (µOCT) images from the tracheal epithelium of living swine. Our common-path fiber-optic probe used gradient-index focusing optics, a selectively coated prism reflector to implement a circular-obscuration apodization for depth-of-focus enhancement, and a common-path reference arm and an ultra-broadbrand supercontinuum laser to achieve high axial resolution. Benchtop characterization demonstrated lateral and axial resolutions of 3.4 μm and 1.7 μm, respectively (in tissue). Mechanical standoff rails flanking the imaging window allowed the epithelial surface to be maintained in focus without disrupting mucus flow. During in vivo imaging, relative motion was mitigated by inflating an airway balloon to hold the standoff rails on the epithelium. Software implemented image stabilization was also implemented during post-processing. The resulting image sequences yielded co-registered quantitative outputs of airway surface liquid and periciliary liquid layer thicknesses, ciliary beat frequency, and mucociliary transport rate, metrics that directly indicate airway epithelial function that have dominated in vitro research in diseases such as cystic fibrosis, but have not been available in vivo. PMID:27446685

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

    PubMed Central

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

    2008-01-01

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

  8. Mucus altering agents as adjuncts for nonviral gene transfer to airway epithelium.

    PubMed

    Ferrari, S; Kitson, C; Farley, R; Steel, R; Marriott, C; Parkins, D A; Scarpa, M; Wainwright, B; Evans, M J; Colledge, W H; Geddes, D M; Alton, E W

    2001-09-01

    Nonviral vectors have been shown to be a safe and valid alternative to recombinant viruses for gene therapy of cystic fibrosis (CF). Nevertheless, gene transfer efficiency needs to be increased before clinical efficacy is likely in man. One barrier to increased efficacy is normal airway mucus. Using an ex vivo model of sheep tracheal epithelium, we show that this barrier can, in part, be overcome by treatment with the mucolytic agents, Nacystelyn or N-acetylcysteine using either a cationic lipid or a cationic polymer as the gene transfer agent. Further, in vivo application of either Nacystelyn or the anticholinergic glycopyrrolate, both clinically used agents, resulted in increased reporter gene expression in the mouse lung, but no significant correction of the bioelectric defect in CF null mice. These results, whilst unlikely to be sufficient in themselves to achieve clinically relevant gene therapy, may be a further useful step in the attainment of this goal. PMID:11571577

  9. THE SPONTANEOUSLY HYPERTENSIVE RAT: AN EXPERIMENTAL MODEL OF SULFUR DIOXIDE-INDUCED AIRWAYS DISEASE

    EPA Science Inventory

    Chronic obstructive pulmonary disease (COPD) is characterized by airway obstruction, inflammation and mucus hypersecretion; features that capture bronchitis, emphysema and often asthma. However, current rodent models do not reflect this human disease. Because genetically predisp...

  10. Acute airway obstruction by Ascaris lumbricoides in a 14-month-old boy.

    PubMed

    Gan, Richard Wei Chern; Gohil, Rohit; Belfield, Katherine; Davies, Patrick; Daniel, Matija

    2014-10-01

    We describe the case of a 14-month-old child with airway obstruction caused by a mature Ascaris lumbricoides worm. The child had been admitted to the paediatric intensive care unit due to overwhelming sepsis, and during the course of his illness developed acute airway obstruction that resolved once the worm was removed from the airway. The Ascaris life-cycle is detailed, and a literature review of patients with airway obstruction due to Ascaris worms is presented. PMID:25129847

  11. Old dilemma: asthma with irreversible airway obstruction or COPD.

    PubMed

    Fattahi, Fatemeh; Vonk, Judith M; Bulkmans, Nicole; Fleischeuer, Ruth; Gouw, Annette; Grünberg, Katrien; Mauad, Thais; Popper, Helmut; Felipe-Silva, Aloisio; Vrugt, Bart; Wright, Joanne L; Yang, Hui-Min; Kocks, Janwillem W H; Hylkema, Machteld N; Postma, Dirkje S; Timens, Wim; Ten Hacken, Nick H T

    2015-11-01

    Older asthmatic patients may develop fixed airway obstruction and clinical signs of chronic obstructive pulmonary disease (COPD). We investigated the added value of pathological evaluation of bronchial biopsies to help differentiate asthma from COPD, taking into account smoking, age, and inhaled corticosteroid (ICS) use. Asthma and COPD patients (24 of each category) were matched for ICS use, age, FEV(1), and smoking habits. Five pulmonary and five general pathologists examined bronchial biopsies using an interactive website, without knowing patient information. They were asked to diagnose asthma or COPD on biopsy findings in both a pairwise and randomly mixed order of cases during four different phases, with intervals of 4-6 weeks, covering a maximal period of 36 weeks. Clinically concordant diagnoses of asthma or COPD varied between 63 %-73 %, without important differences between pairwise vs randomly mixed examination or between general vs pulmonary pathologists. The highest percentage of concordant diagnoses was in young asthmatic patients without ICS use and in COPD patients with ICS use. In non ICS users with fixed airway obstruction, a COPD diagnosis was favored if abnormal presence of glands, squamous metaplasia, and submucosal infiltrate was present and an asthma diagnosis in case of abnormal presence of goblet cells. In ICS users with fixed airway obstruction, abnormal presence of submucosal infiltrates, basement membrane thickening, eosinophils, and glands was associated with asthma. Histological characteristics in bronchial biopsies are reproducibly recognized by pathologists, yet the differentiation by histopathology between asthma and COPD is difficult without information about ICS use. PMID:26369547

  12. Spontaneous intrathyroidal hematoma causing airway obstruction

    PubMed Central

    Best, Corliss A.E.; Dhaliwal, Sandeep; Tam, Samantha; Low, T. Hubert; Hughes, Brian; Fung, Kevin; MacNeil, S. Danielle

    2016-01-01

    Abstract Introduction: Spontaneous thyroid hemorrhage is a rare occurrence that results in pain, discomfort, and occasionally compressive symptoms. Infrequently, extensive thyroid hemorrhage can result in a rapidly expanding hematoma resulting in airway compromise. This is a case of an otherwise healthy young woman, 3 months postpartum, with a slowly expanding spontaneous thyroid hemorrhage that measured at 7 × 5.5 × 5 cm by computed tomography. She ultimately required intubation to manage respiratory distress and subsequently a hemithyroidectomy for definitive treatment. The case presentation is followed by a literature review where known etiologies of thyroid hematoma including traumatic and nontraumatic causes, precipitating anticoagulation, and spontaneous rupture of branches of the external carotid artery are outlined. The potential links to pregnancy are explored. The roles of bedside thyroid ultrasound in the emergency department and lateral neck roentgenogram in diagnosis are explored. The importance of airway management and indications for conservative versus surgical treatments are discussed. Conclusions: This is a case of a spontaneous intrathyroidal hemorrhage, which progressed over days to ultimately cause airway compromise. It is imperative that physicians are educated on the appropriate detection and management of the potentially life-threatening spontaneous thyroid hematoma. PMID:27583841

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

    PubMed

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

    2016-02-01

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

  14. Endotracheal tube defects: Hidden causes of airway obstruction

    PubMed Central

    Sofi, Khalid; El-Gammal, Kariman

    2010-01-01

    Manufacturing defects of endotracheal tube (ETT) are still encountered in anesthesia practice. Many such defects go unnoticed during routine inspection prior to their use. Such defects in ETT may lead to partial or complete airway obstruction in an intubated patient. We report a case of partial airway obstruction with a prepacked, single use, uncuffed ETT due to a manufacturing defect in the form of a plastic meniscus at the distal end of the tube. This case report highlights the significance of standard monitoring of ventilation and the role of a vigilant clinician in detecting such defects in avoiding critical events as can arise from the use of such defective ETTs. It also emphasizes the need for double checking ETTs prior to their use. PMID:20927272

  15. Syphilitic aortic aneurysm presenting with upper airway obstruction.

    PubMed

    Waikittipong, Somchai

    2012-10-01

    Syphilitic aortic aneurysms are uncommon today. A rare case of syphilitic aortic arch aneurysm with successful surgical treatment is reported. A 42-year-old man presented with upper airway obstruction. Chest radiography showed a superior mediastinal mass, and computed tomography revealed a large saccular aortic arch aneurysm that compressed the trachea. Dacron graft replacement of the aortic arch was successfully performed under circulatory arrest with antegrade cerebral perfusion. PMID:23087303

  16. On locating the obstruction in the human upper airway

    NASA Astrophysics Data System (ADS)

    Wang, Yong; Elghobashi, S.

    2013-11-01

    The fluid dynamical properties of the air flow in the human upper airway (UA) are not fully understood at present due to the three-dimensional, patient-specific complex geometry of the airway, flow transition from laminar to turbulent and flow-structure interaction during the breathing cycle. One of the major challenges to surgeons is determining the location of the UA obstruction before performing corrective surgeries. It is quite difficult at present to experimentally measure the instantaneous velocity and pressure at specific points in the human airway. On the other hand, direct numerical simulation (DNS) can predict all the flow properties and resolve all its relevant length- and time-scales. We developed a DNS solver with lattice Boltzmann method (LBM), and used it to investigate the flow in two patient-specific UAs reconstructed from CT scan data. Inspiration and expiration flows through these two airways are studied and compared. Pressure gradient-time signals at different locations in the UAs are used to determine the location of the obstruction. This work was supported by the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH).

  17. Airflow pattern complexity and airway obstruction in asthma.

    PubMed

    Veiga, Juliana; Lopes, Agnaldo J; Jansen, José M; Melo, Pedro L

    2011-08-01

    The scientific and clinical value of a measure of complexity is potentially enormous because complexity appears to be lost in the presence of illness. The authors examined the effect of elevated airway obstruction on the complexity of the airflow (Q) pattern of asthmatic patients analyzing the airflow approximate entropy (ApEnQ). This study involved 11 healthy controls, 11 asthmatics with normal spirometric exams, and 40 asthmatics with mild (14), moderate (14), and severe (12) airway obstructions. A significant (P < 0.02) reduction in the ApEnQ was observed in the asthmatic patients. This reduction was significantly correlated with spirometric indexes of airway obstruction [FEV(1) (%): R = 0.31, P = 0.013] and the total respiratory impedance (R = -0.39; P < 0.002). These results are in close agreement with pathophysiological fundamentals and suggest that the airflow pattern becomes less complex in asthmatic patients, which may reduce the adaptability of the respiratory system to perform the exercise that is associated with daily life activities. This analysis was able to identify respiratory changes in patients with mild obstruction with an adequate accuracy (83%). Higher accuracies were obtained in patients with moderate and severe obstructions. The analysis of airflow pattern complexity by the ApEnQ was able to provide new information concerning the changes associated with asthma. In addition, this analysis was also able to contribute to the detection of the adverse effects of asthma. Because these measurements are easy to perform, such a technique may represent an alternative and/or a complement to other conventional exams to help the clinical evaluations of asthmatic patients. PMID:21565988

  18. Laryngopyocoele presenting with acute airway obstruction

    PubMed Central

    Raine, J I; Allin, D; Golding-Wood, D

    2014-01-01

    A 66-year-old woman was transferred to the emergency department with a left-sided neck lump and fever. She was stridulous with reduced consciousness level and required immediate intubation to protect her airway. CT imaging showed a fluid-filled and air-filled lesion in the left side of the neck; the diagnosis was later confirmed as an infected laryngocoele. She underwent ultrasound guided drainage of the lesion with successful reduction of the neck lump. Following elective tracheostomy she was weaned from ventilation. Subsequent direct endoscopy and biopsy showed no evidence of malignancy or other lesion. She was discharged with permanent tracheostomy to be sustained until definitive surgical resection of the laryngocoele. PMID:25028406

  19. Serum periostin in obstructive airways disease.

    PubMed

    Fingleton, James; Braithwaite, Irene; Travers, Justin; Bowles, Darren; Strik, Rianne; Siebers, Rob; Holweg, Cecile; Matthews, John; Weatherall, Mark; Beasley, Richard

    2016-05-01

    Serum periostin is a potential biomarker of response to therapies that target type 2 inflammation in asthma. The objectives of this study were to describe: 1) the distribution of serum periostin levels in adults with symptomatic airflow obstruction; 2) its relationship with other variables, including type 2 biomarkers; and 3) the effect of inhaled corticosteroids on periostin levels.Serum periostin levels were measured in a cross-sectional study exploring phenotypes and biomarkers in 386 patients aged 18-75 years who reported wheeze and breathlessness in the past 12 months. In 49 ICS-naïve patients, periostin levels were measured again after 12 weeks of budesonide (800 μg·day(-1)).The distribution of serum periostin levels was right skewed (mean±sd 57.3±18.6 ng·mL(-1), median (interquartile range) 54.0 (45.1-65.6) ng·mL(-1), range 15.0-164.7 ng·mL(-1)). Periostin was positively associated with exhaled nitric oxide (Spearman's rho=0.22, p<0.001), blood eosinophil count (Spearman's rho=0.21, p<0.001), and total IgE (Spearman's rho=0.14, p=0.007). The Hodges-Lehmann estimator (95% CI) of change in periostin level after ICS therapy was -4.8 (-6.7- -3.2) ng·mL(-1) (p<0.001).These findings provide data on the distribution of serum periostin in adults with symptomatic airflow obstruction, the weak associations between periostin and other type 2 markers, and the reduction in periostin with inhaled corticosteroid therapy. PMID:26917610

  20. Serum periostin in obstructive airways disease

    PubMed Central

    Braithwaite, Irene; Travers, Justin; Bowles, Darren; Strik, Rianne; Siebers, Rob; Holweg, Cecile; Matthews, John; Weatherall, Mark; Beasley, Richard

    2016-01-01

    Serum periostin is a potential biomarker of response to therapies that target type 2 inflammation in asthma. The objectives of this study were to describe: 1) the distribution of serum periostin levels in adults with symptomatic airflow obstruction; 2) its relationship with other variables, including type 2 biomarkers; and 3) the effect of inhaled corticosteroids on periostin levels. Serum periostin levels were measured in a cross-sectional study exploring phenotypes and biomarkers in 386 patients aged 18–75 years who reported wheeze and breathlessness in the past 12 months. In 49 ICS-naïve patients, periostin levels were measured again after 12 weeks of budesonide (800 μg·day−1). The distribution of serum periostin levels was right skewed (mean±sd 57.3±18.6 ng·mL−1, median (interquartile range) 54.0 (45.1–65.6) ng·mL−1, range 15.0–164.7 ng·mL−1). Periostin was positively associated with exhaled nitric oxide (Spearman's rho=0.22, p<0.001), blood eosinophil count (Spearman's rho=0.21, p<0.001), and total IgE (Spearman's rho=0.14, p=0.007). The Hodges–Lehmann estimator (95% CI) of change in periostin level after ICS therapy was −4.8 (−6.7– −3.2) ng·mL−1 (p<0.001). These findings provide data on the distribution of serum periostin in adults with symptomatic airflow obstruction, the weak associations between periostin and other type 2 markers, and the reduction in periostin with inhaled corticosteroid therapy. PMID:26917610

  1. Airway obstruction after lingual frenulectomy in two infants with Pierre-Robin Sequence.

    PubMed

    Genther, Dane J; Skinner, Margaret L; Bailey, Patti J; Capone, Randolph B; Byrne, Patrick J

    2015-09-01

    Pierre-Robin Sequence (PRS) is defined as the triad of micrognathia, glossoptosis, and cleft palate and affects approximately 1/8500 births. Airway obstruction is common in infants with PRS and results from glossoptosis leading to pharyngeal obstruction. Any procedure that increases the severity of glossoptosis, such as lingual frenulectomy, may increase the risk of obstruction or aggravate existing obstruction. This report discusses two cases of significant airway decompensation after lingual frenulectomy requiring surgical intervention in infants with PRS. We suggest that lingual frenulectomy be contraindicated in infants with PRS or suspected PRS due to the possible increased risk of airway obstruction. PMID:26187546

  2. Clearance of a Mucus Plug

    NASA Astrophysics Data System (ADS)

    Bian, Shiyao; Zheng, Ying; Grotberg, James B.

    2008-11-01

    Mucus plugging may occur in pulmonary airways in asthma, chronic obstructive pulmonary disease (COPD) and cystic fibrosis. How to clear the mucus plug is essential and of fundamental importance. Mucus is known to have a yield stress and a mucus plug behaves like a solid plug when the applied stresses are below its yield stress τy. When the local stresses reaches τy, the plug starts to move and can be cleared out of the lung. It is then of great importance to examine how the mucus plug deforms and what is the minimum pressure required to initiate its movement. The present study used the finite element method (FEM) to study the stress distribution and deformation of a solid mucus plug under different pressure loads using ANSYS software. The maximum shear stress is found to occur near the rear transition region of the plug, which can lead to local yielding and flow. The critical pressure increases linearly with the plug length and asymptotes when the plug length is larger than the half channel width. Experimentally a mucus simulant is used to study the process of plug deformation and critical pressure difference required for the plug to propagate. Consistently, the fracture is observed to start at the rear transition region where the plug core connects the films. However, the critical pressure is observed to be dependent on not only the plug length but also the interfacial shape.

  3. Familial non-cystic fibrosis mucus inspissation of respiratory tract.

    PubMed Central

    Perlman, M; Williams, J; Hirsch, M; Bar-Ziv, J

    1975-01-01

    Perlman, M., Williams, J., Hirsch, M., and Bar-Ziv, J. (1975). Archives of Disease in Childhood, 50, 727. Familial non-cystic fibrosis mucus inspissation of respiratory tract. Two sibs, whose parents are first cousins, have had chronic obstructive airways disease from birth with recurrent otitis media, sinusitis, and mastoiditis. The disease, associated with clinically abnormal mucus, differs from other familial obstructive airways diseases and probably constitutes a new entity. Images FIG. 1 FIG. 2 FIG. 3 FIG. 4 FIG. 5 PMID:1190822

  4. Safety and Efficacy of Thoracic External Beam Radiotherapy After Airway Stenting in Malignant Airway Obstruction

    SciTech Connect

    Rochet, Nathalie; Hauswald, Henrik; Schmaus, Martina; Hensley, Frank; Huber, Peter; Eberhardt, Ralf; Herth, Felix J.; Debus, Juergen; Neuhof, Dirk

    2012-05-01

    Purpose: We retrospectively evaluated the outcome and toxicity of external beam radiotherapy (EBRT) after airway stents were placed in patients treated for malignant airway obstruction. Methods and Materials: Between 2004 and 2009, we performed airway stenting followed by EBRT in 43 patients for symptomatic primary lung cancer (n = 31) or other thoracic malignancies (n = 12). The median time interval between stent placement and first irradiation was 14 days. A median total dose of 50 Gy was delivered. Sixty-seven percent of the patients had reduced performance status (Karnofsky performance score, {<=}70). Results: EBRT had to be stopped prematurely in 16 patients (37%), at a median total dose of 17 Gy, for various reasons. In this group of patients, the survival was poor, with a median overall survival (OS) of only 21 days. Twenty-seven patients (63%) completed radiotherapy as planned, with a median OS of 8.4 months. Fourteen of 43 patients (33%) developed at least one Common Terminology Criteria for Adverse Event of grade 3 to 5. The most common event was a malignant restenosis of the stent leading to asphyxia (n = 7), followed by fistula formation (n = 4), necrosis (n = 3), mediastinitis with abscess (n = 1), secondary nonmalignant airway stenosis (n = 1), and hemoptysis (n = 1). With the exception of one event, all events were associated with a local progression of the tumor. Conclusions: Although the long-term prognosis for patients with malignant airway obstruction is poor, airway stenting combined with EBRT offers a possible therapeutic option, achieving fast relief of acute respiratory distress with an associated antitumor effect, resulting in a potential survival benefit. However, due to local advanced tumor growth, increased rates of adverse events are to be expected, necessitating careful monitoring.

  5. Synthesis and evaluation of airway targeted PLGA nanoparticles for drug delivery in obstructive lung diseases.

    PubMed

    Vij, Neeraj

    2012-01-01

    Chronic airway inflammation is a hallmark of chronic obstructive airway diseases, including asthma, COPD (chronic obstructive pulmonary disease), and CF (cystic fibrosis). It is also a major challenge in delivery and therapeutic efficacy of nano-based delivery systems in these chronic airway conditions as nanoparticle (NP) need to bypass airways defense mechanisms as we recently discussed. NPs which are capable of overcoming airways defense mechanisms should allow targeted drug delivery to disease cells. Over the last decade there has been increasing interest in development of targeted NPs for cancer but relatively little effort on designing novel systems for treating chronic inflammatory and obstructive airway conditions. Here we describe methods for preparing drug loaded multifunctional nanoparticles for targeted delivery to specific cell types in airways. The formulations and methods for selective drug delivery, discussed here are currently under preclinical development in our laboratory for treating chronic airway conditions such as COPD, CF, and asthma. PMID:22791443

  6. Laryngeal lipoma: a rare cause of acute intermittent airway obstruction.

    PubMed

    Deutsch, Peter George; O'Connell, Janet

    2016-01-01

    We present a case of a 62-year-old man with a lipoma in the exceedingly rare location of the larynx, causing intermittent airway obstruction and dysphagia. The lipoma was excised endoscopically with complete resolution of symptoms. Lipomas are relatively common, accounting for 4-5% of all benign tumours in the body. They traditionally occur in areas of large depositions of subcutaneous fat, most frequently the trunk and limbs. They are recognised to occur in the head and neck but these only represent 13-15% of all lipomas. Lipomas are typically asymptomatic unless their impingement of nearby structures causes symptoms. PMID:27107059

  7. Endothelial leukocyte adhesion molecule-1 mediates antigen-induced acute airway inflammation and late-phase airway obstruction in monkeys.

    PubMed Central

    Gundel, R H; Wegner, C D; Torcellini, C A; Clarke, C C; Haynes, N; Rothlein, R; Smith, C W; Letts, L G

    1991-01-01

    This study examines the role of endothelial leukocyte adhesion molecule-1 (ELAM-1) in the development of the acute airway inflammation (cell influx) and late-phase airway obstruction in a primate model of extrinsic asthma. In animals sensitive to antigen, a single inhalation exposure induced the rapid expression of ELAM-1 (6 h) exclusively on vascular endothelium that correlated with the influx of neutrophils into the lungs and the onset of late-phase airway obstruction. In contrast, basal levels of ICAM-1 was constitutively expressed on vascular endothelium and airway epithelium before antigen challenge. After the single antigen exposure, changes in ICAM-1 expression did not correlate with neutrophil influx or the change in airway caliber. This was confirmed by showing that pretreatment with a monoclonal antibody to ICAM-1 did not inhibit the acute influx of neutrophils associated with late-phase airway obstruction, whereas a monoclonal antibody to ELAM-1 blocked both the influx of neutrophils and the late-phase airway obstruction. This study demonstrates a functional role for ELAM-1 in the development of acute airway inflammation in vivo. We conclude that, in primates, the late-phase response is the result of an ELAM-1 dependent influx of neutrophils. Therefore, the regulation of ELAM-1 expression may provide a novel approach to controlling the acute inflammatory response, and thereby, affecting airway function associated with inflammatory disorders, including asthma. Images PMID:1717514

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

    PubMed Central

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

    2016-01-01

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

  9. Spatial organization of cilia tufts governs airways mucus transport: Application to severe asthma

    NASA Astrophysics Data System (ADS)

    Khelloufi, Mustapha Kamel; Gras, Delphine; Chanez, Pascal; Viallat, Annie

    2014-11-01

    We study the coupling between both density and spatial repartition of beating cilia tufts, and the coordinated transport of mucus in an in-vitro epithelial model. We use a fully differentiated model epithelium in air liquid interface (ALI) obtained from endo-bronchial biopsies from healthy subjects and patients with asthma. The asthma phenotype is known to persist in the model. Mucus transport is characterized by the trajectories and velocities of microscopic beads incorporated in the mucus layer. When the beating cilia tufts density is higher than dc = 11/100 × 100 μm2 a spherical spiral coordinated mucus transport is observed over the whole ALI chamber (radius = 6 mm). Below dc, local mucus coordinated transport is observed on small circular domains on the epithelium surface. We reveal that the radii of these domains scale with the beating cilia tufts density with a power 3.7. Surprisingly, this power law is independent on cilia beat frequency, concentration and rheological properties of mucus for healthy subject and patient with asthma. The rotating or linear mucus transport is related to dispersion of the cilia tufts on the epithelium surface. We show that impaired mucus transport observed in severe asthma model epithelia is due to a drastic lack and dysfunction of cilia tufts. The author acknowledges the support of the French Agence Nationale de la Recherche (ANR) under reference ANR-13-BSV5-0015-01.

  10. EBM84 attenuates airway inflammation and mucus hypersecretion in an ovalbumin-induced murine model of asthma.

    PubMed

    Shin, In Sik; Lee, Mee Young; Jeon, Woo Young; Shin, Na Ra; Seo, Chang Seob; Ha, Hyekyung

    2013-04-01

    EBM84 is a traditional herbal medicine and a combination of extracts obtained from Pinellia ternata and Zingiber officinale. It is traditionally used to treat vomiting, nausea, sputum and gastrointestinal disorders, and functions is an effective expectorant. In this study, we evaluated the protective effects of EBM84 on asthmatic responses, particularly mucus hypersecretion in an ovalbumin (OVA)-induced murine model of asthma. We also analyzed EBM84 composition using high performance liquid chromatography. Animals were sensitized on days 0 and 14 via intraperitoneal injection using 20 µg OVA. On days 21, 22 and 23 after initial sensitization, the mice received an airway challenge with OVA (1% w/v in PBS) for 1 h using an ultrasonic nebulizer (NE-U12). EBM84 was administered by gavage to the mice at doses of 16.9, 33.8 and 67.5 mg/kg once daily from days 18 to 23. EBM84 administration significantly lowered elevated levels of interleukin (IL)-4, IL-13, eotaxin and immunoglobulin (Ig)E in the bronchoalveolar lavage fluid or plasma. Airway inflammation and mucus hypersecretion were attenuated following EBM84 administration. EBM84 also inhibited the overexpression of mucin 5AC (MUC5AC) induced by OVA challenge in lung tissue. This result was consistent with the immunohistochemistry results. Our results indicate that EBM84 effectively inhibited airway inflammation and mucus hypersecretion via the downregulation of T helper 2 (Th2) cytokines, which reduced MUC5AC expression. Therefore, EBM84 has potential as a useful medicine for the treatment of allergic asthma. PMID:23403738

  11. Prenatal secondhand cigarette smoke promotes Th2 polarization and impairs goblet cell differentiation and airway mucus formation.

    PubMed

    Singh, Shashi P; Gundavarapu, Sravanthi; Peña-Philippides, Juan C; Rir-Sima-ah, Jules; Mishra, Neerad C; Wilder, Julie A; Langley, Raymond J; Smith, Kevin R; Sopori, Mohan L

    2011-11-01

    Parental, particularly maternal, smoking increases the risk for childhood allergic asthma and infection. Similarly, in a murine allergic asthma model, prenatal plus early postnatal exposure to secondhand cigarette smoke (SS) exacerbates airways hyperreactivity and Th2 responses in the lung. However, the mechanism and contribution of prenatal versus early postnatal SS exposure on allergic asthma remain unresolved. To identify the effects of prenatal and/or early postnatal SS on allergic asthma, BALB/c dams and their offspring were exposed gestationally and/or 8-10 wk postbirth to filtered air or SS. Prenatal, but not postnatal, SS strongly increased methacholine and allergen (Aspergillus)-induced airway resistance, Th2 cytokine levels, and atopy and activated the Th2-polarizing pathway GATA3/Lck/ERK1/2/STAT6. Either prenatal and/or early postnatal SS downregulated the Th1-specific transcription factor T-bet and, surprisingly, despite high levels of IL-4/IL-13, dramatically blocked the allergen-induced mucous cell metaplasia, airway mucus formation, and the expression of mucus-related genes/proteins: Muc5ac, γ-aminobutyric acid A receptors, and SAM pointed domain-containing Ets-like factor. Given that SS/nicotine exposure of normal adult mice promotes mucus formation, the results suggested that fetal and neonatal lung are highly sensitive to cigarette smoke. Thus, although the gestational SS promotes Th2 polarization/allergic asthma, it may also impair and/or delay the development of fetal and neonatal lung, affecting mucociliary clearance and Th1 responses. Together, this may explain the increased susceptibility of children from smoking parents to allergic asthma and childhood respiratory infections. PMID:21930963

  12. Toward the modeling of mucus draining from human lung: role of airways deformation on air-mucus interaction

    PubMed Central

    Mauroy, Benjamin; Flaud, Patrice; Pelca, Dominique; Fausser, Christian; Merckx, Jacques; Mitchell, Barrett R.

    2015-01-01

    Chest physiotherapy is an empirical technique used to help secretions to get out of the lung whenever stagnation occurs. Although commonly used, little is known about the inner mechanisms of chest physiotherapy and controversies about its use are coming out regularly. Thus, a scientific validation of chest physiotherapy is needed to evaluate its effects on secretions. We setup a quasi-static numerical model of chest physiotherapy based on thorax and lung physiology and on their respective biophysics. We modeled the lung with an idealized deformable symmetric bifurcating tree. Bronchi and their inner fluids mechanics are assumed axisymmetric. Static data from the literature is used to build a model for the lung's mechanics. Secretions motion is the consequence of the shear constraints apply by the air flow. The input of the model is the pressure on the chest wall at each time, and the output is the bronchi geometry and air and secretions properties. In the limit of our model, we mimicked manual and mechanical chest physiotherapy techniques. We show that for secretions to move, air flow has to be high enough to overcome secretion resistance to motion. Moreover, the higher the pressure or the quicker it is applied, the higher is the air flow and thus the mobilization of secretions. However, pressures too high are efficient up to a point where airways compressions prevents air flow to increase any further. Generally, the first effects of manipulations is a decrease of the airway tree hydrodynamic resistance, thus improving ventilation even if secretions do not get out of the lungs. Also, some secretions might be pushed deeper into the lungs; this effect is stronger for high pressures and for mechanical chest physiotherapy. Finally, we propose and tested two a dimensional numbers that depend on lung properties and that allow to measure the efficiency and comfort of a manipulation. PMID:26300780

  13. Toward the modeling of mucus draining from human lung: role of airways deformation on air-mucus interaction.

    PubMed

    Mauroy, Benjamin; Flaud, Patrice; Pelca, Dominique; Fausser, Christian; Merckx, Jacques; Mitchell, Barrett R

    2015-01-01

    Chest physiotherapy is an empirical technique used to help secretions to get out of the lung whenever stagnation occurs. Although commonly used, little is known about the inner mechanisms of chest physiotherapy and controversies about its use are coming out regularly. Thus, a scientific validation of chest physiotherapy is needed to evaluate its effects on secretions. We setup a quasi-static numerical model of chest physiotherapy based on thorax and lung physiology and on their respective biophysics. We modeled the lung with an idealized deformable symmetric bifurcating tree. Bronchi and their inner fluids mechanics are assumed axisymmetric. Static data from the literature is used to build a model for the lung's mechanics. Secretions motion is the consequence of the shear constraints apply by the air flow. The input of the model is the pressure on the chest wall at each time, and the output is the bronchi geometry and air and secretions properties. In the limit of our model, we mimicked manual and mechanical chest physiotherapy techniques. We show that for secretions to move, air flow has to be high enough to overcome secretion resistance to motion. Moreover, the higher the pressure or the quicker it is applied, the higher is the air flow and thus the mobilization of secretions. However, pressures too high are efficient up to a point where airways compressions prevents air flow to increase any further. Generally, the first effects of manipulations is a decrease of the airway tree hydrodynamic resistance, thus improving ventilation even if secretions do not get out of the lungs. Also, some secretions might be pushed deeper into the lungs; this effect is stronger for high pressures and for mechanical chest physiotherapy. Finally, we propose and tested two a dimensional numbers that depend on lung properties and that allow to measure the efficiency and comfort of a manipulation. PMID:26300780

  14. Peripheral airways obstruction in idiopathic pulmonary artery hypertension (primary).

    PubMed

    Fernandez-Bonetti, P; Lupi-Herrera, E; Martinez-Guerra, M L; Barrios, R; Seoane, M; Sandoval, J

    1983-05-01

    The mechanical properties of the lung were studied in ten nonsmokers with idiopathic pulmonary artery hypertension (IPAH) (mean pulmonary artery pressure 65.7 +/- 30 mm Hg). In the routine lung test, residual volume was found to be abnormal (greater than 120 percent of the predicted) in seven patients, and measured airway resistance was normal in eight out of the ten patients. A decreased FEF 75-85 percent, abnormal values for the helium-air flow ratios and increased closing capacities were documented in eight of ten patients in whom lung elastic recoil was normal (six of ten) or increased (four of ten). These features suggest peripheral airways obstruction (PAO) which was also supported by histopathologic findings in three cases (one biopsy and two necropsies). The observed changes in lung compliance could be related to the behavior of the coupling of the air-space and vascular compartments. The etiology of PAO in IPAH patients is not known, but our results indicate that both the peripheral airways and the pulmonary circulation are affected. The knowledge of PAO in IPAH patients could help to better understand the observed V/Q inequality in this entity. PMID:6839814

  15. Impending Complete Airway Obstruction from a Reinforced Orotracheal Tube: a Case Report.

    PubMed

    Hosseinzadeh, Nima; Samadi, Shahram; Jafari Javid, Mihan; Takzare, Alireza

    2015-01-01

    Reinforced tubes are commonly used to minimize the opportunity of upper airway obstruction in patients at risk. There are a few reports of the airway obstruction resulted from kinked reinforced tubes. This report describes the obstruction of a reinforced tube in an adult patient who underwent tonsillectomy. Under general anesthesia; an armoured endotracheal tube was inserted into the trachea uneventfully. A few minutes after starting the surgery, the anesthesia machine detected a high airway pressure and an increased ETCO2 (end-tidal CO2) up to 50 mmHg. Further evaluation showed spiral wire damage resulted from Mouth Gag device that led to airway obstruction. Early anticipation of the complications leads to proper management of such critical and life threatening complications and prevention of hypoxia, hypercapnia, pneumothorax, and pulmonary edema. Based on our experience using an armoured endotracheal tube in tonsillectomy does not guarantee a safe airway and intensive monitoring is necessary. PMID:26553090

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

    PubMed

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

    2015-12-01

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

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

    PubMed

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

    2015-04-01

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

  18. Impact of obstructive apnea syndrome on upper airway respiratory muscles.

    PubMed

    Svanborg, Eva

    2005-07-28

    This article reviews studies of upper airway muscles in humans, with emphasis on muscle fiber structural and electrophysiological changes observed in patients with obstructive sleep apnea syndrome (OSAS). The concept of OSAS as a progressive disease is discussed and also possible causes. These include local nervous lesions in the upper airway, both motor and sensory. Previous muscle biopsy studies have given evidence for motor neuron lesions such as, e.g., the phenomenon of type grouping in histological sections. New data obtained with concentric needle EMG recordings from the palatopharyngeus muscles are also presented. In 10/12 OSAS patients there were typical findings indicating motor neuropathy (reduced EMG activity at maximal voluntary effort, long and polyphasic motor-unit potentials and, in two cases, spontaneous denervation activity), whereas such findings were only present in 3/15 patients with habitual snoring. This supports the hypothesis that progression from habitual snoring to the clinical disease of OSAS could be attributed to peripheral neurogenic lesions. PMID:16054444

  19. Airway Microbiome Dynamics in Exacerbations of Chronic Obstructive Pulmonary Disease

    PubMed Central

    Sethi, Sanjay; Murphy, Timothy; Nariya, Snehal; Boushey, Homer A.; Lynch, Susan V.

    2014-01-01

    Specific bacterial species are implicated in the pathogenesis of exacerbations of chronic obstructive pulmonary disease (COPD). However, recent studies of clinically stable COPD patients have demonstrated a greater diversity of airway microbiota, whose role in acute exacerbations is unclear. In this study, temporal changes in the airway microbiome before, at the onset of, and after an acute exacerbation were examined in 60 sputum samples collected from subjects enrolled in a longitudinal study of bacterial infection in COPD. Microbiome composition and predicted functions were examined using 16S rRNA-based culture-independent profiling methods. Shifts in the abundance (≥2-fold, P < 0.05) of many taxa at exacerbation and after treatment were observed. Microbiota members that were increased at exacerbation were primarily of the Proteobacteria phylum, including nontypical COPD pathogens. Changes in the bacterial composition after treatment for an exacerbation differed significantly among the therapy regimens clinically prescribed (antibiotics only, oral corticosteroids only, or both). Treatment with antibiotics alone primarily decreased the abundance of Proteobacteria, with the prolonged suppression of some microbiota members being observed. In contrast, treatment with corticosteroids alone led to enrichment for Proteobacteria and members of other phyla. Predicted metagenomes of particular microbiota members involved in these compositional shifts indicated exacerbation-associated loss of functions involved in the synthesis of antimicrobial and anti-inflammatory products, alongside enrichment in functions related to pathogen-elicited inflammation. These trends reversed upon clinical recovery. Further larger studies will be necessary to determine whether specific compositional or functional changes detected in the airway microbiome could be useful indicators of exacerbation development or outcome. PMID:24850358

  20. Continuous positive airway pressure titration in infants with severe upper airway obstruction or bronchopulmonary dysplasia

    PubMed Central

    2013-01-01

    Abstracta Introduction Noninvasive continuous positive airway pressure (CPAP) is recognized as an effective treatment for severe airway obstruction in young children. The aim of the present study was to compare a clinical setting with a physiological setting of noninvasive CPAP in infants with nocturnal alveolar hypoventilation due to severe upper airway obstruction (UAO) or bronchopulmonary dysplasia (BPD). Methods The breathing pattern and respiratory muscle output of all consecutive infants due to start CPAP in our noninvasive ventilation unit were retrospectively analysed. CPAP set on clinical noninvasive parameters (clinical CPAP) was compared to CPAP set on the normalization or the maximal reduction of the oesophageal pressure (Poes) and transdiaphragmatic pressure (Pdi) swings (physiological CPAP). Expiratory gastric pressure (Pgas) swing was measured. Results The data of 12 infants (mean age 10 ± 8 mo) with UAO (n = 7) or BPD (n = 5) were gathered. The mean clinical CPAP (8 ± 2 cmH2O) was associated with a significant decrease in Poes and Pdi swings. Indeed, Poes swing decreased from 31 ± 15 cmH2O during spontaneous breathing to 21 ± 10 cmH2O during CPAP (P < 0.05). The mean physiological CPAP level was 2 ± 2 cmH2O higher than the mean clinical CPAP level and was associated with a significantly greater improvement in all indices of respiratory effort (Poes swing 11 ± 5 cm H2O; P < 0.05 compared to clinical CPAP). Expiratory abdominal activity was present during the clinical CPAP and decreased during physiological CPAP. Conclusions A physiological setting of noninvasive CPAP, based on the recording of Poes and Pgas, is superior to a clinical setting, based on clinical noninvasive parameters. Expiratory abdominal activity was present during spontaneous breathing and decreased in the physiological CPAP setting. PMID:23889768

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

    PubMed

    Bates, Jason H T

    2016-09-01

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

  2. Importance of slow vital capacity in the detection of airway obstruction*

    PubMed Central

    de Barros, Ana Raquel Gonçalves; Pires, Margarida Batista; Raposo, Nuno Miguel Ferreira

    2013-01-01

    OBJECTIVE: To investigate the presence of airway obstruction by determining the FEV1/FVC and FEV1/slow vital capacity (SVC) ratios. METHODS: This was a quantitative, retrospective cross-sectional study. The sample comprised 1,084 individuals who underwent spirometry and plethysmography in a central hospital in Lisbon, Portugal. The study sample was stratified into six groups, by pulmonary function. RESULTS: The analysis of the FEV1/FVC ratio revealed the presence of airway obstruction in 476 individuals (43.9%), compared with 566 individuals (52.2%) for the analysis of the FEV1/SVC ratio. In the airway obstruction, airway obstruction plus lung hyperinflation, and mixed pattern groups, the difference between SVC and FVC (SVC − FVC) was statistically superior to that in the normal pulmonary function, reduced FEF, and restrictive lung disease groups. The SVC − FVC parameter showed a significant negative correlation with FEV1 (in % of the predicted value) only in the airway obstruction plus lung hyperinflation group. CONCLUSIONS: The FEV1/SVC ratio detected the presence of airway obstruction in more individuals than did the FEV1/FVC ratio; that is, the FEV1/SVC ratio is more reliable than is the FEV1/FVC ratio in the detection of obstructive pulmonary disease. PMID:23857701

  3. Total respiratory resistance and reactance in patients with upper airway obstruction.

    PubMed

    van Noord, J A; Wellens, W; Clarysse, I; Cauberghs, M; Van de Woestijne, K P; Demedts, M

    1987-09-01

    In 18 patients with upper airway obstruction, we measured dynamic lung volumes, maximal flows, airway resistance (Raw), and total respiratory resistance (Rrs) and reactance (Xrs) at various frequencies by means of a forced oscillation method. Patients were classified according to the site and the type of the obstruction. The values of Raw, Rrs and Xrs were tightly correlated and reflected the overall importance of the obstruction. In comparison with patients with chronic obstructive pulmonary disease the values of Rrs tend to be higher and to be influenced more by support of the cheeks during the measurement. These differences are not diagnostic, however. PMID:3622024

  4. Therapeutic approaches to mucus hypersecretion.

    PubMed

    Yuta, Atsushi; Baraniuk, James N

    2005-05-01

    Mucolytic and related agents have been in use since prehistoric times. Although widely prescribed and used extensively in over-the-counter preparations, their efficacy and mechanisms of action remain in doubt. These agents belong to several distinct chemical classes. Mucolytic agents such as N-acetyl-cysteine are thiols with a free-sulfhydryl group. They are assumed to break disulfide bonds between gel-forming mucins and thus reduce mucus viscosity. Mucokinetic agents are thiols with a blocked sulfhydryl group. Expectorants such as guaifenesin increase mucus secretion. They may act as irritants to gastric vagal receptors, and recruit efferent parasympathetic reflexes that cause glandular exocytosis of a less viscous mucus mixture. Cough may be provoked. This combination may flush tenacious, congealed mucopurulent material from obstructed small airways and lead to a temporary improvement in dyspnea or the work of breathing. The roles of anticholinergic agents, DNase, and other drugs are also discussed with regard to their roles in reducing mucus production in rhinitis and other airway diseases. PMID:15842963

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

    NASA Astrophysics Data System (ADS)

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

    1996-04-01

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

  6. A risk for obstruction of the airways in the parenteral use of levomepromazine with benzodiazepine.

    PubMed

    Hatta, K; Takahashi, T; Nakamura, H; Yamashiro, H; Endo, H; Kito, K; Saeki, T; Masui, K; Yonezawa, Y

    1998-07-01

    Arrhythmogenic effects of phenothiazines appear to be associated with sudden death, whereas respiratory complications have received little attention. In this report we describe 5 cases with accompanying obstruction of the airways after intramuscular injections of levomepromazine (LPZ), a potent sedative phenothiazine, in combination with intravenous injections of benzodiazepine (BZ) during a 3-month period in a psychiatric intensive care unit. Two out of 5 cases were unpredictable because obstruction of the airways occurred 2 hours or more after the last injection. As compared with patients who received parenteral (intravenous or intramuscular) injections during the same period, the dose of intramuscular LPZ was significantly large in the 5 cases with obstruction of the airways. All 5 of these cases received intramuscular LPZ 0.52 mg/kg or more. In contrast, there was no patient with obstruction of the airways who received only intramuscular LPZ, the combination of LPZ and HDL, or BZ and HDL. The occurrence of obstruction of the airways among patients who received both intramuscular LPZ and intravenous BZ was significantly higher than among patients who received other drug regimes. These preliminary results suggest that the intramuscular use of LPZ with intravenous BZ may be a risk for obstruction of the airways. PMID:9754846

  7. Infant Mandibular Distraction for Upper Airway Obstruction: A Clinical Audit

    PubMed Central

    Adhikari, Ashim N.; Heggie, Andrew A.C.; Shand, Jocelyn M.; Bordbar, Patrishia; Pellicano, Anastasia

    2016-01-01

    Background: Mandibular distraction osteogenesis (MDO) is an effective method of treating upper airway obstruction (UAO) in micrognathic infants. The short-term outcomes include relief of UAO, avoidance of tracheostomy, and prompt discharge from hospital. However, it is a significant surgical procedure with potential associated morbidities. This study describes a cohort of infants managed using MDO over a twelve-year period. Methods: A retrospective chart review was undertaken for children who had MDO before the age of 5 years between 2000 and 2012. This was followed by a clinical review of the same cohort specifically looking for dental anomalies, nerve injuries, and scar cosmesis. Results: Seventy-three children underwent MDO at a mean age of 2 months [interquartile range (IQR), 1.7–4.2] for nonsyndromic infants and 3.3 months (IQR, 2.1–7.4) for those with syndromes. Infants were discharged from hospital, on average, 15 days after procedure. After MDO, of the 9 who were previously tracheostomy dependent, 5 (56%) were decannulated within 12 months and none of the nontracheostomy-dependent children required further airway assistance. The majority of children required supplemental feeding preoperatively but, 12 months postoperatively, 97% of the nonsyndromic infants fed orally. Thirty-nine children (53%) were reviewed clinically [median age, 5.1 y (IQR, 3.9–6.5)] with 18 being syndromic. Many of the mandibular first permanent and second primary molars had developmental defects, but there was a low rate of neurosensory deficit and good scar cosmesis. Conclusions: This study contributes further to the evidence base underpinning the management of micrognathic infants with UAO. PMID:27536491

  8. CORRELATES BETWEEN HUMAN LUNG INJURY AFTER PARTICLE EXPOSURE AND RECURRENT AIRWAY OBSTRUCTION IN THE HORSE

    EPA Science Inventory

    Characteristics of the clinical presentation, physiologic changes, and pathology of the human response to particulate matter (PM) are comparable to inflammatory airway disease (lAD) and recurrent airway obstruction (RAO)lheaves in the horse. Both present with symptoms of cough,...

  9. Glottic and skull indices in canine brachycephalic airway obstructive syndrome

    PubMed Central

    2014-01-01

    Background Forty dogs presented for brachycephalic airway obstructive syndrome with laryngeal collapse not over 1st degree (saccule eversion) underwent glottis endoscopic and radiographic skull measurements before surgery. Fifteen Pugs, fifteen French and ten English Bulldogs were included. The goals were prospectively to compare three common brachycephalic breeds for anatomical differences regarding glottis and skull measurements, and to assess if any correlation between glottis and skull measurements was present. Linear measurements were used to obtain glottis and skull indices. Correlations between glottis and skull indices and glottic measurements were evaluated. Finally, glottis indices were compared among the three breeds. Results No correlation was found for glottis and skull indices. The glottic index differed among the three breeds (smaller in Pugs and higher in English Bulldogs), ultimately representing a morphologic indicator of the different larynx shape in the three breeds (more rounded in English Bulldogs, more elliptical in Pugs and in-between in French Bulldogs). Conclusions The lack of correlation between skull/glottic indices does not support skull morphology as predictor of glottic morphology. As Pugs had the lowest glottic index, it may be speculated that Pugs’ original narrow glottic width may predispose to further progressive respiratory deterioration more easily than in the other two breeds. PMID:24410902

  10. Automated detection of mucus plugs within bronchial tree in MSCT images

    NASA Astrophysics Data System (ADS)

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

    2007-03-01

    Pulmonary diseases characterized by chronic airway inflammation, such as Chronic Obstructive Pulmonary (COPD), result in abnormal bronchial wall thickening, lumen dilatation and mucus plugs. Multi-Slice Computed Tomography (MSCT) allows for assessment of these abnormalities, even in airways that are obliquely oriented to the scan plane. Chronic airway inflammation typically results in limitations of airflow, allowing for the accumulation of mucus, especially in the distal airways. In addition to obstructing airways, retained secretions make the airways prone to infection. Patients with chronic airway disease are clinically followed over time to assess disease progression and response to treatment. In this regard, the ability to obtain an automatic standardized method to rapidly and objectively assess the entire airway tree morphologically, including the extent of mucus plugging, would be of particular clinical value. We have developed a method to automatically detect the presence and location of mucus plugs within the peripheral airways. We first start with segmentation of the bronchial tree using a previously developed method. The skeleton-based tree structure is then computed and each terminal branch is individually extended using an adaptive threshold algorithm. We compute a local 2-dimensional model, based on airway luminal diameter and wall thickness. We then select a few points along the principal axis beyond the terminal branches, to extract 2D cross sections for correlation with a model of mucus plugging. Airway shape is validated with a correlation value, and the lumen distribution is analyzed and compared to the model. A high correlation indicates the presence of a mucus plug. We tested our method on 5 datasets containing a total of 40 foci of mucoid impaction. Preliminary results show sensitivity of 77.5% with a specificity of 98.2% and positive predictive value of 66%.

  11. Fluoroscopic and computed tomographic features of the pharyngeal airway in obstructive sleep apnea.

    PubMed

    Suratt, P M; Dee, P; Atkinson, R L; Armstrong, P; Wilhoit, S C

    1983-04-01

    Because it has been suggested that patients with obstructive sleep apnea have a narrower pharyngeal airway than normal persons, we performed lateral fluoroscopy and computed tomographic (CT) scans of the pharynx in patients with this syndrome. Fluoroscopy in 6 sleeping patients showed that the obstruction always began during inspiration when the soft palate touched the tongue and posterior pharyngeal wall. The CT scans in 9 awake subjects demonstrated that the narrowest section of the airway in patients and in control subjects was the region posterior to the soft palate. The cross-sectional area of this region was significantly narrower in patients than it was in control subjects (p less than 0.001). Because a narrow airway would be more likely to collapse during inspiration than a normal one would (Bernoulli's Principle), we conclude that the narrow airways we observed in awake patients may be an important contributing factor in the pathogenesis of obstructive sleep apnea. PMID:6838055

  12. Dyspnea and dysphagia from upper airway obstruction after occipitocervical fusion in the pediatric age group.

    PubMed

    Huang, Meng; Gonda, David D; Briceño, Valentina; Lam, Sandi K; Luerssen, Thomas G; Jea, Andrew

    2015-04-01

    Upper airway obstruction resulting from overflexion of the craniocervical junction after occipitocervical fusion is a rare but potentially life-threatening complication and is associated with morbidity. The authors retrospectively reviewed the medical records and diagnostic images of 2 pediatric patients who underwent occipitocervical fusion by the Neuro-Spine Program at Texas Children's Hospital and experienced dyspnea and/or dysphagia from new upper airway obstruction in the postoperative period. Patient demographics, operative data, and preoperative and postoperative occiput-C2 angles were recorded. A review of the literature for similar complications after occipitocervical fusion was performed. A total of 13 cases of prolonged upper airway obstruction after occipitocervical fusion were analyzed. Most of these cases involved adults with rheumatoid arthritis. To the best of the authors' knowledge, there have been no previous reports of prolonged upper airway obstruction in children after an occipitocervical fusion. Fixation of the neck in increased flexion (-18° to -5°) was a common finding among these adult and pediatric cases. The authors' cases involved children with micrognathia and comparatively large tongues, which may predispose the oropharynx to obstruction with even the slightest amount of increased flexion. Close attention to a satisfactory fixation angle (occiput-C2 angle) is necessary to avoid airway obstruction after an occipitocervical fusion. Children with micrognathia are particularly sensitive to changes in flexion at the craniocervical junction after occipitocervical fixation. PMID:25828489

  13. Treatment of bronchial airway obstruction using a rotating tip microdebrider: a case report

    PubMed Central

    Kennedy, Marcus P; Morice, Rodolfo C; Jimenez, Carlos A; Eapen, George A

    2007-01-01

    Background Central airway obstruction is a common complication of lung cancer. The microdebrider is a new device available for treatment of central airway obstruction. Case Description We report a case a 59-yr-old male with T3N2M1 non-small cell lung cancer with malignant distal left mainstem obstruction treated successfully with a novel elongated rotating tip microdebrider via rigid bronchoscopy with sufficient length to reach distal bronchial lesions. Discussion and Conclusion The microdebrider is an excellent addition to the spectrum of interventions available for the management of central airway obstruction with advantages including accuracy and immediate removal of debris without a need for separate suctioning or limitation in oxygenation. PMID:17386099

  14. Diagnostic Accuracy of Obstructive Airway Adult Test for Diagnosis of Obstructive Sleep Apnea

    PubMed Central

    Gasparini, Giulio; Vicini, Claudio; De Benedetto, Michele; Salamanca, Fabrizio; Sorrenti, Giovanni; Romandini, Mario; Bosi, Marcello; Saponaro, Gianmarco; Foresta, Enrico; Laforì, Andreina; Meccariello, Giuseppe; Bianchi, Alessandro; Toraldo, Domenico Maurizio; Campanini, Aldo; Montevecchi, Filippo; Rizzotto, Grazia; Cervelli, Daniele; Moro, Alessandro; Arigliani, Michele; Gobbi, Riccardo; Pelo, Sandro

    2015-01-01

    Rationale. The gold standard for the diagnosis of Obstructive Sleep Apnea (OSA) is polysomnography, whose access is however reduced by costs and limited availability, so that additional diagnostic tests are needed. Objectives. To analyze the diagnostic accuracy of the Obstructive Airway Adult Test (OAAT) compared to polysomnography for the diagnosis of OSA in adult patients. Methods. Ninety patients affected by OSA verified with polysomnography (AHI ≥ 5) and ten healthy patients, randomly selected, were included and all were interviewed by one blind examiner with OAAT questions. Measurements and Main Results. The Spearman rho, evaluated to measure the correlation between OAAT and polysomnography, was 0.72 (p < 0.01). The area under the ROC curve (95% CI) was the parameter to evaluate the accuracy of the OAAT: it was 0.91 (0.81–1.00) for the diagnosis of OSA (AHI ≥ 5), 0.90 (0.82–0.98) for moderate OSA (AHI ≥ 15), and 0.84 (0.76–0.92) for severe OSA (AHI ≥ 30). Conclusions. The OAAT has shown a high correlation with polysomnography and also a high diagnostic accuracy for the diagnosis of OSA. It has also been shown to be able to discriminate among the different degrees of severity of OSA. Additional large studies aiming to validate this questionnaire as a screening or diagnostic test are needed. PMID:26636102

  15. Solid fuel smoke exposure and risk of obstructive airways disease.

    PubMed

    Qorbani, Mostafa; Yunesian, Masud

    2012-01-01

    This study was designed to investigate whether there is an association between Obstructive Airways Disease (OAD) and indoor exposure to baking home-made bread smoke (BHBS) in ground oven at home. In this hospital-based case-control study, 83 patients with OAD (cases) were compared with 72 patients without any known pulmonary diseases from the surgical ward (controls) who were frequently matched with cases on age. The interview was performed using the modified questionnaire recommended by the "American Thoracic Society". The questionnaire comprised of demographic information, occupational history, cigarette smoking and indoor exposure to BHBS in ground oven at home. The exposure to BHBS was considered both as a dichotomous and quantitative variable (number of years being exposed to smoke) and the population attributable fraction (PAF) was estimated due to BHBS exposure. The percentage of indoor exposure to BHBS was measured as 51.8% and 30.6% in the cases and the controls, respectively. The average years of exposure to BHBS was 20.46 years (SD: 11.60) for the cases and 15.38 years (SD: 13.20) for the controls. The univariate analysis comparing the cases and the controls showed that exposure to BHBS (as a binary variable) and occupational exposure to dust was significantly associated with OAD. In the multivariate model, only exposure to BHBS was associated with OAD (OR=2.22, 95%CI = 1.14-4.35). Duration of exposure to BHBS (as a quantitative variable) was significantly associated with OAD in the univariate model. In the multivariate model, only the duration of exposure to BHBS (years) showed a significant association with OAD (OR=1.04, 95% CI=1.01-1.08). Population attributable risk due to BHBS exposure was equal to 28.5%. PMID:23369551

  16. Effects of acid aerosol exposure on the surface properties of airway mucus

    SciTech Connect

    Lee, M.M.; Schuerch, S.; Roth, S.H.

    1995-12-31

    It was hypothesized that the mucous layer lining the tracheas of rats and guinea pigs contains surfactant material capable of lowering the air/mucus surface tension, {gamma}, and that exposure to an irritant aerosol would raise the {gamma}. The {gamma} of the surface film was measured directly by a spreading droplet technique and indirectly by displacement of polymethyl methacrylate particles into the aqueous layer. The morphology of the mucous film was examined by electron microscopy after nonaqueous fixation. {gamma} was 33.3 {plus_minus} 0.70 (SE) mN/m and 32.3 {plus_minus} 0.68 (SE) mN/m for the normal rat and guinea pig trachea, respectively. Exposure for 4 h to aerosols of sulfuric acid (94.1 {plus_minus} 18.68 (SD) and 43.3 {plus_minus} 4.57 (SD) mg/m{sup 3}) caused a several-fold increase in thickness of the mucous layer with exudation of protein-like material. The osmiophilic surfactant film at the air/mucus interface became irregularly thickened and multilayered. Despite these morphological changes {gamma} remained low, 33.2 {plus_minus} 0.43 (SE) mN/m and 32.6 {plus_minus} 0.60 (SE) mN/m for rats and guinea pigs, respectively, and displacement of particles into the subphase was not compromised. The results indicate that rodent tracheas are able to maintain a low surface tension in the presence of injury. 24 refs., 9 figs.

  17. A comparison of a new mucolytic N-acetylcysteine L-lysinate with N-acetylcysteine: airway epithelial function and mucus changes in dog.

    PubMed

    Tomkiewicz, R P; App, E M; De Sanctis, G T; Coffiner, M; Maes, P; Rubin, B K; King, M

    1995-12-01

    A newly synthesized mucolytic agent, N-acetylcysteine L-lysinate (Nacystelyn) was studied. Tracheal mucus velocity (TMV), transepithelial potential difference (PD), rheological properties, and ion content of collected airway secretions were evaluated in six healthy mongrel dogs after placebo, Nacystelyn (NAL) and acetylcysteine (NAC) metered dose inhaler (MDI) aerosols. Although TMV was increased and viscoelasticity decreased after both treatments, the treatment effect with NAL was significantly greater. Furthermore, NAL increased the negative PD and CI- content of secretions in the trachea, an effect not observed after NAC. Both compounds increased ciliary beat frequency (CBF) on the frog palate at a concentration range similar to that approximated in dog airways. The increased mucociliary clearance could be partially explained by favourable rheological changes combined with stimulation of CBF. Since both compounds break disulfide bonds in mucus polymers, the greater change in mucus rheology and clearance rate after NAL, without change in water content, could be explained by the increase in CI- content. Nacystelyn appears to combine different modes of action which synergistically cause an increase in the clearance rate of airway secretions. PMID:8819180

  18. Mucus Hyperconcentration as a Unifying Aspect of the Chronic Bronchitic Phenotype.

    PubMed

    Button, Brian; Anderson, Wayne H; Boucher, Richard C

    2016-04-01

    Abnormalities in mucus production and qualitative properties such as mucus hydration are central to the pathophysiology of airway disease including cystic fibrosis, asthma, and chronic bronchitis. In vitro air-liquid interface epithelial cell cultures demonstrate direct relationships between mucociliary transport, periciliary liquid (PCL) height, and mucus concentration (expressed as percent solids or partial osmotic pressure). In health, the osmotic modulus/pressure of the PCL exceeds that of the mucus layer, resulting in efficient, low-friction movement of mucus. In disease, through multiple mechanisms, the osmotic pressure of the mucus begins to exceed basal PCL values, resulting in compression of the cilia and slowing of mucus transport. The in vivo data in both cystic fibrosis and chronic bronchitis parallel in vitro data demonstrating that when mucus osmotic pressure is increased, mucociliary clearance is decreased. In chronic bronchitis, there is a direct correlation between FEV1 and percent solids of mucus, demonstrating a strong relationship between disease progression and mucus abnormalities. Animal models, based mechanistically on raised sodium absorption (and therefore water absorption) from airway surfaces, mimic the pathophysiology of chronic obstructive pulmonary disease. Collectively, these data suggest the importance of mucus concentration in the pathogenesis of airway disease. It is important to understand the precise mechanisms that result in mucus hyperconcentration, for example, mucin overproduction versus abnormal regulation of ion/water transport, which may be unique to and characteristic of each disease phenotype. The measurement of mucus concentration may be a simple method to diagnose chronic bronchitis, monitor its progression, and serve as a biomarker for development of new therapies. PMID:27115951

  19. A Series of Congenital High Airway Obstruction Syndrome – Classic Imaging Findings

    PubMed Central

    Dey, Amit Kumar; Alam, Shah; Mittal, Kartik; Thakkar, Hemangini

    2016-01-01

    Congenital high airway obstruction syndrome (CHAOS) is a very rare entity with very poor prognosis in which upper airway is intrinsically obstructed, the most common reason being laryngeal atresia. In summary prenatal early diagnosis of patients with CHAOS is necessary so that perinatal management can be undertaken successfully or elective termination of pregnancy can be undertaken. The fetoscopic approach may be a life saving modality in a subset of CHAOS patients. Involving a multidisciplinary team comprising of paediatricians, radiologists, obstetricians and anaesthesiologists increases the efficiency of management. PMID:27134966

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

    PubMed Central

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

    2014-01-01

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

  1. Elective use of the Ventrain for upper airway obstruction during high-frequency jet ventilation.

    PubMed

    Fearnley, Robert A; Badiger, Sheela; Oakley, Richard J; Ahmad, Imran

    2016-09-01

    The safety of high pressure source ventilation (jet ventilation) is dependent upon upper airway patency to facilitate adequate passive expiration and prevent increasing intrathoracic pressure and its associated deleterious sequelae. Distortions in airway anatomy may make passive expiration inadequate or impossible in some patients. We report the elective use of the Ventrain device to provide ventilation in a clinical setting of upper airway obstruction in a patient with post radiation fibrosis that had previously prevented passive expiration during attempted high pressure source ventilation. PMID:27555171

  2. Computational Modeling of Airway Obstruction in Sleep Apnea in Down Syndrome: A Feasibility Study.

    PubMed

    Mylavarapu, Goutham; Subramaniam, Dhananjay; Jonnagiri, Raghuvir; Gutmark, Ephraim J; Fleck, Robert J; Amin, Raouf S; Mahmoud, Mohamed; Ishman, Stacey L; Shott, Sally R

    2016-07-01

    Current treatment options are successful in 40% to 60% of children with persistent obstructive sleep apnea after adenotonsillectomy. Residual obstruction assessments are largely subjective and do not clearly define multilevel obstruction. We endeavor to use computational fluid dynamics to perform virtual surgery and assess airflow changes in patients with Down syndrome and persistent obstructive sleep apnea. Three-dimensional airway models were reconstructed from respiratory-gated computed tomography and magnetic resonance imaging. Virtual surgeries were performed on 10 patients, mirroring actual surgeries. They demonstrated how surgical changes affect airflow resistance. Airflow and upper airway resistance was calculated from computational fluid dynamics. Virtual and actual surgery outcomes were compared with obstructive apnea-hypopnea index values. Actual surgery successfully treated 6 of 10 patients (postoperative obstructive apnea-hypopnea index <5). In 8 of 10 subjects, both apnea-hypopnea index and the calculated upper airway resistance after virtual surgery decreased as compared with baseline values. This is a feasibility and proof-of-concept study. Further studies are needed before using these techniques in surgical planning. PMID:27048669

  3. Toward the modeling of mucus draining from the human lung: role of the geometry of the airway tree

    NASA Astrophysics Data System (ADS)

    Mauroy, Benjamin; Fausser, Christian; Pelca, Dominique; Merckx, Jacques; Flaud, Patrice

    2011-10-01

    Mucociliary clearance and cough are the two main natural mucus draining methods in the bronchial tree. If they are affected by a pathology, they can become insufficient or even ineffective, then therapeutic draining of mucus plays a critical role to keep mucus levels in the lungs acceptable. The manipulations of physical therapists are known to be very efficient clinically but they are mostly empirical since the biophysical mechanisms involved in these manipulations have never been studied. We develop in this work a model of mucus clearance in idealized rigid human bronchial trees and focus our study on the interaction between (1) tree geometry, (2) mucus physical properties and (3) amplitude of flow rate in the tree. The mucus is considered as a Bingham fluid (gel-like) which is moved upward in the tree thanks to its viscous interaction with air flow. Our studies point out the important roles played both by the geometry and by the physical properties of mucus (yield stress and viscosity). More particularly, the yield stress has to be overcome to make mucus flow. Air flow rate and yield stress determine the maximal possible mucus thickness in each branch of the tree at equilibrium. This forms a specific distribution of mucus in the tree whose characteristics are strongly related to the multi-scaled structure of the tree. The behavior of any mucus distribution is then dependent on this distribution. Finally, our results indicate that increasing air flow rates ought to be more efficient to drain mucus out of the bronchial tree while minimizing patient discomfort.

  4. The effect of increased lung volume in chronic obstructive pulmonary disease on upper airway obstruction during sleep.

    PubMed

    Biselli, Paolo; Grossman, Peter R; Kirkness, Jason P; Patil, Susheel P; Smith, Philip L; Schwartz, Alan R; Schneider, Hartmut

    2015-08-01

    Patients with chronic obstructive pulmonary disease (COPD) exhibit increases in lung volume due to expiratory airflow limitation. Increases in lung volumes may affect upper airway patency and compensatory responses to inspiratory flow limitation (IFL) during sleep. We hypothesized that COPD patients have less collapsible airways inversely proportional to their lung volumes, and that the presence of expiratory airflow limitation limits duty cycle responses to defend ventilation in the presence of IFL. We enrolled 18 COPD patients and 18 controls, matched by age, body mass index, sex, and obstructive sleep apnea disease severity. Sleep studies, including quantitative assessment of airflow at various nasal pressure levels, were conducted to determine upper airway mechanical properties [passive critical closing pressure (Pcrit)] and for quantifying respiratory timing responses to experimentally induced IFL. COPD patients had lower passive Pcrit than their matched controls (COPD: -2.8 ± 0.9 cmH2O; controls: -0.5 ± 0.5 cmH2O, P = 0.03), and there was an inverse relationship of subject's functional residual capacity and passive Pcrit (-1.7 cmH2O/l increase in functional residual capacity, r(2) = 0.27, P = 0.002). In response to IFL, inspiratory duty cycle increased more (P = 0.03) in COPD patients (0.40 to 0.54) than in controls (0.41 to 0.51) and led to a marked reduction in expiratory time from 2.5 to 1.5 s (P < 0.01). COPD patients have a less collapsible airway and a greater, not reduced, compensatory timing response during upper airway obstruction. While these timing responses may reduce hypoventilation, it may also increase the risk for developing dynamic hyperinflation due to a marked reduction in expiratory time. PMID:26048975

  5. Pharyngeal abscess presenting with upper airway obstruction and atlanto-axial subluxation in a small infant.

    PubMed

    Brookes, A; Moriarty, A

    2000-05-01

    We describe an infant who presented with a combination of upper airway obstruction and atlanto-axial subluxation, secondary to a pharyngeal abscess resulting from cosmetic ear piercing. This combination posed a number of difficulties for the anasthetist and a detailed plan was formulated to prepare the child for anasthesia. PMID:10792140

  6. Hurler's syndrome with cor pulmonale secondary to obstructive sleep apnoea treated by continuous positive airway pressure.

    PubMed

    Chan, D; Li, A M; Yam, M C; Li, C K; Fok, T F

    2003-01-01

    A 6-year-old boy with Hurler's syndrome presented with right heart failure and pulmonary hypertension secondary to severe obstructive sleep apnoea. Both his sleep apnoea and cor pulmonale were effectively controlled with continuous positive airway pressure therapy. PMID:12969215

  7. 21 CFR 868.5115 - Device to relieve acute upper airway obstruction.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Device to relieve acute upper airway obstruction. 868.5115 Section 868.5115 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5115 Device...

  8. 21 CFR 868.5115 - Device to relieve acute upper airway obstruction.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Device to relieve acute upper airway obstruction. 868.5115 Section 868.5115 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5115 Device...

  9. 21 CFR 868.5115 - Device to relieve acute upper airway obstruction.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Device to relieve acute upper airway obstruction. 868.5115 Section 868.5115 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5115 Device...

  10. 21 CFR 868.5115 - Device to relieve acute upper airway obstruction.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Device to relieve acute upper airway obstruction. 868.5115 Section 868.5115 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5115 Device...

  11. 21 CFR 868.5115 - Device to relieve acute upper airway obstruction.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Device to relieve acute upper airway obstruction. 868.5115 Section 868.5115 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5115 Device...

  12. Pulmonary effects of expiratory-assisted small-lumen ventilation during upper airway obstruction in pigs.

    PubMed

    Ziebart, A; Garcia-Bardon, A; Kamuf, J; Thomas, R; Liu, T; Schad, A; Duenges, B; David, M; Hartmann, E K

    2015-10-01

    Novel devices for small-lumen ventilation may enable effective inspiration and expiratory ventilation assistance despite airway obstruction. In this study, we investigated a porcine model of complete upper airway obstruction. After ethical approval, we randomly assigned 13 anaesthetised pigs either to small-lumen ventilation following airway obstruction (n = 8) for 30 min, or to volume-controlled ventilation (sham setting, n = 5). Small-lumen ventilation enabled adequate gas exchange over 30 min. One animal died as a result of a tension pneumothorax in this setting. Redistribution of ventilation from dorsal to central compartments and significant impairment of the distribution of ventilation/perfusion occurred. Histopathology demonstrated considerable lung injury, predominantly through differences in the dorsal dependent lung regions. Small-lumen ventilation maintained adequate gas exchange in a porcine airway obstruction model. The use of this technique for 30 min by inexperienced clinicians was associated with considerable end-expiratory collapse leading to lung injury, and may also carry the risk of severe injury. PMID:26179167

  13. Usefulness of Digital Tomosynthesis for the Detection of Airway Obstruction: A Case Report of Bronchial Carcinosarcoma

    PubMed Central

    Park, Sung-Joon; Choo, Ji Yung; Lee, Ki Yeol; Kim, Je-Hyeong; Choi, Jung-Woo; Yeom, Suk Keu; Kim, Baek Hyun

    2015-01-01

    Bronchial carcinosarcoma is a very rare malignant tumor that is composed of carcinomatous and sarcomatous elements. We describe the first case in which digital tomosynthesis was useful for the evaluation of airway obstruction by bronchial carcinosarcoma that was overlooked on initial chest radiography. PMID:25381829

  14. Supra-Epiglottic Upper Airway Volume in Elderly Patients with Obstructive Sleep Apnea Hypopnea Syndrome

    PubMed Central

    Abdirahman Mohamed Moussa, Syad; Celle, Sébastien; Laurent, Bernard; Barthélémy, Jean-Claude; Barral, Fabrice-Guy; Roche, Frédéric

    2016-01-01

    Objective Small upper airway measurements areas and high body mass index are recognized risk factors for obstructive sleep apnea syndrome (OSAS) in non-elderly populations; however, there is limited information regarding elderly patients. We evaluated whether upper airway volume is associated with OSAS and OSAS treated with continuous positive airway pressure (CPAP) treatment and whether BMI is correlated with upper airway volume and measurements in elderly subjects. Methods In 60 volunteers aged 75.58±0.9 years: 20 OSAS, 20 OSAS chronically treated with CPAP, and 20 controls, semi-automatic segmentation, retropalatal distance and transverse diameter of the supra-epiglottic upper airway were evaluated using 3DT1-weighted magnetic resonance imaging. Anteroposterior to transverse diameter ratio was defined as retropalatar diameter/transverse diameter. Results There were no significant differences in supra-epiglottic upper airway volume between OSAS, CPAP treated patients, and controls. There were significant differences in retropalatal distance and anteroposterior to transverse diameter ratio between OSAS, CPAP treated patients, and controls (P = 0.008 and P<0.0001 respectively). There was a significant correlation between body mass index and retropalatal distance (P<0.05) but not with supra-epiglottic upper airway volume. Conclusion In elderly subjects, OSAS and body mass index are not associated with changes in supra-epiglottic upper airway volume but are associated with modification of pharynx shape. PMID:27336305

  15. Prolonged partial upper airway obstruction during sleep - an underdiagnosed phenotype of sleep-disordered breathing.

    PubMed

    Anttalainen, Ulla; Tenhunen, Mirja; Rimpilä, Ville; Polo, Olli; Rauhala, Esa; Himanen, Sari-Leena; Saaresranta, Tarja

    2016-01-01

    Obstructive sleep apnea syndrome (OSAS) is a well-recognized disorder conventionally diagnosed with an elevated apnea-hypopnea index. Prolonged partial upper airway obstruction is a common phenotype of sleep-disordered breathing (SDB), which however is still largely underreported. The major reasons for this are that cyclic breathing pattern coupled with arousals and arterial oxyhemoglobin saturation are easy to detect and considered more important than prolonged episodes of increased respiratory effort with increased levels of carbon dioxide in the absence of cycling breathing pattern and repetitive arousals. There is also a growing body of evidence that prolonged partial obstruction is a clinically significant form of SDB, which is associated with symptoms and co-morbidities which may partially differ from those associated with OSAS. Partial upper airway obstruction is most prevalent in women, and it is treatable with the nasal continuous positive pressure device with good adherence to therapy. This review describes the characteristics of prolonged partial upper airway obstruction during sleep in terms of diagnostics, pathophysiology, clinical presentation, and comorbidity to improve recognition of this phenotype and its timely and appropriate treatment. PMID:27608271

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

    PubMed

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

    2014-08-01

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

  17. Movement Distribution: A New Measure of Sleep Fragmentation in Children with Upper Airway Obstruction

    PubMed Central

    Coussens, Scott; Baumert, Mathias; Kohler, Mark; Martin, James; Kennedy, Declan; Lushington, Kurt; Saint, David; Pamula, Yvonne

    2014-01-01

    Study Objectives: To develop a measure of sleep fragmentation in children with upper airway obstruction based on survival curve analysis of sleep continuity. Design: Prospective repeated measures. Setting: Hospital sleep laboratory. Participants: 92 children aged 3.0 to 12.9 years undergoing 2 overnight polysomnographic (PSG) sleep studies, 6 months apart. Subjects were divided into 3 groups based on their obstructive apnea and hypopnea index (OAHI) and other upper airway obstruction (UAO) symptoms: primary snorers (PS; n = 24, OAHI < 1), those with obstructive sleep apnea syndrome (OSAS; n = 20, OAHI ≥ 1) and non-snoring controls (C; n = 48, OAHI < 1). Interventions: Subjects in the PS and OSAS groups underwent tonsillectomy and adenoidectomy between PSG assessments. Measurements and Results: Post hoc measures of movement and contiguous sleep epochs were exported and analyzed using Kaplan-Meier estimates of survival to generate survival curves for the 3 groups. Statistically significant differences were found between these group curves for sleep continuity (P < 0.05) when using movement events as the sleep fragmenting event, but not if stage 1 NREM sleep or awakenings were used. Conclusion: Using conventional indices of sleep fragmentation in survival curve analysis of sleep continuity does not provide a useful measure of sleep fragmentation in children with upper airway obstruction. However, when sleep continuity is defined as the time between gross body movements, a potentially useful clinical measure is produced. Citation: Coussens S, Baumert M, Kohler M, Martin J, Kennedy D, Lushington K, Saint D, Pamula Y. Movement distribution: a new measure of sleep fragmentation in children with upper airway obstruction. SLEEP 2014;37(12):2025-2034. PMID:25325486

  18. Origins of and implementation concepts for upper airway stimulation therapy for obstructive sleep apnea.

    PubMed

    Strohl M D, Kingman P; Baskin M D, Jonathan; Lance M D, Colleen; Ponsky M D, Diana; Weidenbecher M D, Mark; Strohl B A, Madeleine; Yamauchi M D, Motoo

    2016-07-01

    Upper airway stimulation, specifically hypoglossal (CN XII) nerve stimulation, is a new, alternative therapy for patients with obstructive sleep apnea hypopnea syndrome who cannot tolerate positive airway pressure, the first-line therapy for symptomatic patients. Stimulation therapy addresses the cause of inadequate upper airway muscle activation for nasopharyngeal and oropharyngeal airway collapse during sleep. The purpose of this report is to outline the development of this first-in-class therapy and its clinical implementation. Another practical theme is assessment of the features for considering a surgically implanted device and the insight as to how both clinical and endoscopic criteria increase the likelihood of safe and durable outcomes for an implant and how to more generally plan for management of CPAP-intolerant patients. A third theme is the team building required among sleep medicine and surgical specialties in the provision of individualized neurostimulation therapy. PMID:27424823

  19. Upper Airway Stimulation for Obstructive Sleep Apnea: Past, Present, and Future

    PubMed Central

    Dedhia, Raj C.; Strollo, Patrick J.; Soose, Ryan J.

    2015-01-01

    Obstructive sleep apnea (OSA) is an increasingly prevalent clinical problem with significant effects on both personal and public health. Continuous positive airway pressure (CPAP) has demonstrated excellent efficacy and low morbidity; long-term adherence rates approach 50%. Although traditional upper airway surgical procedures target the anatomic component of obstruction, upper airway stimulation tackles the twin goals of improving anatomic and neuromuscular pathology. After decades of trials demonstrating proof of concept of hypoglossal nerve stimulation in animal and human subjects, the results of a large multicenter, prospective trial were recently published. The trial demonstrated that hypoglossal nerve stimulation led to significant improvements in objective and subjective measurements of the severity of OSA. This novel approach is the first to combine sleep surgery techniques with a titratable medical device for the treatment of OSA. Further research is required to define optimal patient selection and device performance and to demonstrate long-term effectiveness. Citation: Dedhia RC, Strollo PJ, Soose RJ. Upper airway stimulation for obstructive sleep apnea: past, present, and future. SLEEP 2015;38(6):899– 906. PMID:25409109

  20. On locating the obstruction in the upper airway via numerical simulation

    PubMed Central

    Wang, Yong; Elghobashi, S.

    2014-01-01

    The fluid dynamical properties of the air flow in the upper airway (UA) are not fully understood at present due to the three-dimensional (3D) patient-specific complex geometry of the airway, flow transition from laminar to turbulent and flow-structure interaction during the breathing cycle. It is quite difficult at present to experimentally measure the instantaneous velocity and pressure at specific points in the human airway. On the other hand, direct numerical simulation (DNS) can predict all the flow properties and resolve all its relevant length- and time-scales. We developed a DNS solver with the state-of-the-art lattice Boltzmann method (LBM), and used it to investigate the flow in two patient-specific UAs reconstructed from CT scan data. Inspiration and expiration flows through these two airways are studied. The time-averaged first spatial derivative of pressure (pressure gradient), ∂p/∂z, is used to locate the region of the UA obstruction. But the time-averaged second spatial derivative, ∂2p/∂z2, is used to pinpoint the exact location of the obstruction. The present results show that the DNS-LBM solver can be used to obtain accurate flow details in the UA and is a powerful tool to locate its obstruction. PMID:24389271

  1. A Persistent and Diverse Airway Microbiota Present during Chronic Obstructive Pulmonary Disease Exacerbations

    PubMed Central

    Huang, Yvonne J.; Kim, Eugenia; Cox, Michael J.; Brodie, Eoin L.; Brown, Ron; Wiener-Kronish, Jeanine P.

    2010-01-01

    Abstract Acute exacerbations of chronic obstructive pulmonary disease (COPD) are a major source of morbidity and contribute significantly to healthcare costs. Although bacterial infections are implicated in nearly 50% of exacerbations, only a handful of pathogens have been consistently identified in COPD airways, primarily by culture-based methods, and the bacterial microbiota in acute exacerbations remains largely uncharacterized. The aim of this study was to comprehensively profile airway bacterial communities using a culture-independent microarray, the 16S rRNA PhyloChip, of a cohort of COPD patients requiring ventilatory support and antibiotic therapy for exacerbation-related respiratory failure. PhyloChip analysis revealed the presence of over 1,200 bacterial taxa representing 140 distinct families, many previously undetected in airway diseases; bacterial community composition was strongly influenced by the duration of intubation. A core community of 75 taxa was detected in all patients, many of which are known pathogens. Bacterial community diversity in COPD airways is substantially greater than previously recognized and includes a number of potential pathogens detected in the setting of antibiotic exposure. Comprehensive assessment of the COPD airway microbiota using high-throughput, culture-independent methods may prove key to understanding the relationships between airway bacterial colonization, acute exacerbation, and clinical outcomes in this and other chronic inflammatory airway diseases. PMID:20141328

  2. Computed tomographic imaging of dogs with primary laryngeal or tracheal airway obstruction.

    PubMed

    Stadler, Krystina; Hartman, Susan; Matheson, Jodi; O'Brien, Robert

    2011-01-01

    Seventeen dogs with clinical signs attributable to nonneoplastic obstruction of the larynx, trachea, or large bronchi underwent computed tomography (CT) imaging. In 16 of the 17 dogs, CT was performed without general anesthesia using a positioning device. Fifteen of these 16 dogs were imaged without sedation or general anesthesia. Three-dimensional (3D) internal rendering was performed on each image set based on lesion localization determined by routine image planes. Visual laryngeal examination, endoscopy, video fluoroscopy, and necropsy were used for achieving the cause of the upper airway obstruction. The CT and 3D internal rendering accurately indicated the presence and cause of upper airway obstruction in all dogs. CT findings indicative of laryngeal paralysis included failure to abduct the arytenoid cartilages, narrowed rima glottis, and air-filled laryngeal ventricles. Laryngeal collapse findings depended on the grade of collapse and included everted laryngeal saccules, collapse of the cuneiform processes and corniculate processes, and narrowed rima glottis. Trachea abnormalities included hypoplasia, stenosis, or collapse syndrome. The CT findings in tracheal hypoplasia consisted of a severely narrowed lumen throughout the entire length. Tracheal stenosis was represented by a circumferential decrease in tracheal lumen size limited to one region. Tracheal collapse syndrome was diagnosed by severe asymmetric narrowing. Lobar bronchi collapse appeared in CT images as a narrowed asymmetric lumen diameter. CT imaging of unanesthetized dogs with upper airway obstruction compares favorably with traditional definitive diagnostic methods. PMID:21447037

  3. Ultrasound in obstructive lung diseases: the effect of airway obstruction on diaphragm kinetics. A short pictorial essay.

    PubMed

    Zanforlin, Alessandro; Smargiassi, Andrea; Inchingolo, Riccardo; Valente, Salvatore; Ramazzina, Emilio

    2015-12-01

    The ultrasound study of the chest is showing a continuous development. This technique could be helpful in managing several chest diseases, but it is limited to the acoustic windows provided by intercostal spaces and by the inability to study healthy lung parenchyma and all intra-parenchymal diseases such as chronic obstructive lung disease (COPD), because the interaction between ventilated lung and ultrasound generates only artifacts. Currently, there are few applications of ultrasound that are useful in COPD, with recent studies providing some innovation potentially useful in clinical practice. The similarity of the trend between the time/volume curve of spirometry and the M-mode representation of diaphragm during forced breath allowed to identify the M-mode Index of Obstruction (MIO), an index obtained from the ratio between forced diaphragmatic excursion in the first second (FEDE1, cm) and the maximal expiratory diaphragmatic excursion (EDEMax, cm). MIO has shown a linear correlation with the ratio between forced expiratory volume in the first second (FEV1) and vital capacity (VC), used in spirometry to identify airways obstruction. The value of MIO seems to be lower in patients affected by airways obstruction as showed by a recent study. The technique is easy to learn and fast to perform and the analysis could be provided with any ultrasound machine equipped with M-mode. In conclusion, these findings, if confirmed by other studies, could suggest a new add-on screening tool for obstructive lung diseases, in particular COPD, that could be performed during a routine abdominal ultrasound exam. PMID:26550063

  4. Effect of upper airway obstruction in acute stroke on functional outcome at 6 months

    PubMed Central

    Turkington, P; Allgar, V; Bamford, J; Wanklyn, P; Elliott, M

    2004-01-01

    Background: The aim of this study was to determine whether upper airway obstruction occurring within the first 24 hours of stroke onset has an effect on outcome following stroke at 6 months. Traditional definitions used for obstructive sleep apnoea (OSA) are arbitrary and may not apply in the acute stroke setting, so a further aim of the study was to redefine respiratory events and to assess their impact on outcome. Methods: 120 patients with acute stroke underwent a sleep study within 24 hours of onset to determine the severity of upper airway obstruction (respiratory disturbance index, RDI-total study). Stroke severity (Scandinavian Stroke Scale, SSS) and disability (Barthel score) were also recorded. Each patient was subsequently followed up at 6 months to determine morbidity and mortality. Results: Death was independently associated with SSS (OR (95% CI) 0.92 (0.88 to 0.95), p<0.00001) and RDI-total study (OR (95% CI) 1.07 (1.03 to 1.12), p<0.01). The Barthel index was independently predicted by SSS (p = 0.0001; r = 0.259; 95% CI 0.191 to 0.327) and minimum oxygen saturation during the night (p = 0.037; r = 0.16; 95% CI 0.006 to 0.184). The mean length of the respiratory event most significantly associated with death at 6 months was 15 seconds (sensitivity 0.625, specificity 0.525) using ROC curve analysis. Conclusion: The severity of upper airway obstruction appears to be associated with a worse functional outcome following stroke, increasing the likelihood of death and dependency. Longer respiratory events appear to have a greater effect. These data suggest that long term outcome might be improved by reducing upper airway obstruction in acute stroke. PMID:15115859

  5. Tube Law of the Pharyngeal Airway in Sleeping Patients with Obstructive Sleep Apnea

    PubMed Central

    Genta, Pedro R.; Edwards, Bradley A.; Sands, Scott A.; Owens, Robert L.; Butler, James P.; Loring, Stephen H.; White, David P.; Wellman, Andrew

    2016-01-01

    Study Objectives: Obstructive sleep apnea (OSA) is characterized by repetitive pharyngeal collapse during sleep. However, the dynamics of pharyngeal narrowing and re-expansion during flow-limited breathing are not well described. The static pharyngeal tube law (end-expiratory area versus luminal pressure) has demonstrated increasing pharyngeal compliance as luminal pressure decreases, indicating that the airway would be sucked closed with sufficient inspiratory effort. On the contrary, the airway is rarely sucked closed during inspiratory flow limitation, suggesting that the airway is getting stiffer. Therefore, we hypothesized that during inspiratory flow limitation, as opposed to static conditions, the pharynx becomes stiffer as luminal pressure decreases. Methods: Upper airway endoscopy and simultaneous measurements of airflow and epiglottic pressure were performed during natural nonrapid eye movement sleep. Continuous positive (or negative) airway pressure was used to induce flow limitation. Flow-limited breaths were selected for airway cross-sectional area measurements. Relative airway area was quantified as a percentage of end-expiratory area. Inspiratory airway radial compliance was calculated at each quintile of epiglottic pressure versus airway area plot (tube law). Results: Eighteen subjects (14 males) with OSA (apnea-hypopnea index = 57 ± 27 events/h), aged 49 ± 8 y, with a body mass index of 35 ± 6 kg/m2 were studied. A total of 163 flow limited breaths were analyzed (9 ± 3 breaths per subject). Compliances at the fourth (2.0 ± 4.7 % area/cmH2O) and fifth (0.0 ± 1.7 % area/cmH2O) quintiles were significantly lower than the first (12.2 ± 5.5 % area/cmH2O) pressure quintile (P < 0.05). Conclusions: The pharyngeal tube law is concave (airway gets stiffer as luminal pressure decreases) during respiratory cycles under inspiratory flow limitation. Citation: Genta PR, Edwards BA, Sands SA, Owens RL, Butler JP, Loring SH, White DP, Wellman A. Tube law of

  6. Serious neonatal airway obstruction with massive congenital sublingual ranula and contralateral occurrence

    PubMed Central

    George, Manish M.; Mirza, Omar; Solanki, Kohmal; Goswamy, Jay; Rothera, Michael P.

    2015-01-01

    Background Congenital ranulas seldom occur, with bilateral presentation and prenatal diagnosis reported very rarely. We believe this is the first reported case of a neonate with a antenally diagnosed massive congenital ranula, who went on to develop a non-contiguous contralateral ranula, both contributing to obstruction in a complex paediatric airway. Case report A female neonate was born to a non-primagravid mother via a planned elective caesarean section due to a lower facial defect and oral cyst. Antenatal aspiration of the pseudocyst was performed under ultrasound guidance with limited success. In the immediate post-natal period a poor airway was observed and the cyst was subsequently marsupialised. With the development of macroglossia secondary to oedema and tongue base collapse the airway was secured through surgical tracheostomy. A subsequent ultrasound scan revealed the presence of a second solitary cystic mass on the contralateral side. After careful excision of the contralateral pseudocyst, tongue function improved, with the resolution of a safe airway which permitted successful decannulation. A planned definitive procedure antenatally did not result in the anticipated improvement in function. However the subsequent development of a second non-contiguous pseudocyst and further surgical management resulted in a safe airway, improved masticator function and the ability to thrive. Conclusions The prenatal diagnosis of congenital ranulas have been seldom reported, with no reported cases of contralateral occurrence and airway obstruction from an intraoral ranula. This rare case highlights the need for a well considered contingency plan when surgery is required for a neonatal airway at risk. PMID:25984300

  7. Mucus clearance, MyD88-dependent and MyD88-independent immunity modulate lung susceptibility to spontaneous bacterial infection and inflammation

    PubMed Central

    Livraghi-Butrico, Alessandra; Kelly, E. Jane; Klem, Erich R.; Dang, Hong; Wolfgang, Matthew C.; Boucher, Richard C.; Randell, Scott H.; O’Neal, Wanda K.

    2012-01-01

    It has been postulated that mucus stasis is central to the pathogenesis of obstructive lung diseases. In Scnn1b-transgenic (Scnn1b-Tg+) mice, airway-targeted overexpression of the epithelial Na+ channel β subunit causes airway surface dehydration, which results in mucus stasis and inflammation. Bronchoalveolar lavage from neonatal Scnn1b-Tg+ mice, but not wild-type littermates, contained increased mucus, bacteria, and neutrophils, which declined with age. Scnn1b-Tg+ mice lung bacterial flora included environmental and oropharyngeal species, suggesting inhalation and/or aspiration as routes of entry. Genetic deletion of the Toll/Interleukin-1 receptor adapter molecule MyD88 in Scnn1b-Tg+ mice did not modify airway mucus obstruction, but caused defective neutrophil recruitment and increased bacterial infection, which persisted into adulthood. Scnn1b-Tg+ mice derived into germ-free conditions exhibited mucus obstruction similar to conventional Scnn1b-Tg+ mice and sterile inflammation. Collectively, these data suggest that dehydration-induced mucus stasis promotes infection, compounds defects in other immune mechanisms, and alone is sufficient to trigger airway inflammation. PMID:22419116

  8. [Use of cryoextraction in different types of airway obstruction].

    PubMed

    Franke, K-J; Nilius, G; Rühle, K-H

    2010-06-01

    With the development of mechanically stable cryoprobes, direct endoscopic removal of tissue from the bronchial system with cryotherapy is now possible. Tissue is frozen to the tip of the probe and removed by pulling on the probe together with the fiberscope. This procedure, also referred to as cryoextraction, additionally provides good quality biopsy specimens for histopathological examination. We report here on four patients with different forms of bronchial obstruction, in whom cryoextraction was performed for rapid recanalization. In addition to the immediate effect, the procedure has few complications and is cost-effective. Indications were mucoid impaction, foreign body aspiration, removal of suprastomal granulation tissue prior to decannulation after prolonged mechanical ventilation, and obstruction of the trachea and the main bronchi by a carcinosarcoma. In the latter case, the diagnosis was additionally based on a specimen obtained by cryobiopsy. PMID:20391320

  9. Diagnosis of airway obstruction in the elderly: contribution of the SARA study

    PubMed Central

    Sorino, Claudio; Battaglia, Salvatore; Scichilone, Nicola; Pedone, Claudio; Antonelli-Incalzi, Raffaele; Sherrill, Duane; Bellia, Vincenzo

    2012-01-01

    Background The choice between lower limit of normal or fixed value of forced expiratory volume in one second/forced vital capacity ratio (FEV1/FVC) < 0.70 as the criterion for confirming airway obstruction is an open issue. In this study, we compared the criteria of lower limit of normal and fixed FEV1/FVC for diagnosis of airway obstruction, with a focus on healthy elderly people. Methods We selected 367 healthy nonsmoking subjects aged 65–93 years from 1971 participants in the population-based SARA (Salute Respiratoria nell’Anziano, Italian for “Respiratory Health in the Elderly”) study, analyzed their spirometric data, and tested the relationship between spirometric indices and anthropometric variables. The lower limit of normal for FEV1/FVC was calculated as the fifth percentile of the normal distribution for selected subjects. Results While FEV1 and FVC decreased significantly with aging, the relationship between FEV1/FVC and age was not statistically significant in men or women. The lower limit of normal for FEV1/FVC was 0.65 in men and 0.67 in women. Fifty-five participants (15%) had FEV1/FVC < 0.70 and would have been inappropriately classified as obstructed according to the Global Initiative for Obstructive Lung Disease, American Thoracic Society/European Respiratory Society, and Canadian guidelines on chronic obstructive pulmonary disease. By applying different FEV1/FVC thresholds for the different age groups, as previously proposed in the literature, (0.70 for <70 years, 0.65 for 70–80 years, and 0.60 for >80 years) the percentage of patients classified as obstructed decreased to 6%. No subjects older than 80 years had an FEV1/FVC < 0.60. Conclusion The present results confirm the inadequacy of FEV1/FVC < 0.70 as a diagnostic criterion for airway obstruction after the age of 65 years. FEV1/FVC < 0.65 and <0.67 (for men and women, respectively) could identify subjects with airway obstruction in such a population. Further reduction of the

  10. Total resistance and reactance in patients with respiratory complaints with and without airways obstruction.

    PubMed

    Clément, J; Làndsér, F J; Van de Woestijne, K P

    1983-02-01

    A comparison was made of the frequency dependence of total respiratory resistance, (Rrs), and reactance (Xrs), determined by a forced oscillation technique in 442 healthy subjects and in 126 patients with respiratory complaints, with or without slight airways obstruction. The comparison was performed by means of a discriminant analysis. The latter demonstrated that the Rrs and Xrs data, measured between 8 and 24 Hz, of patients differ from those of healthy subjects primarily by a decrease of Rrs with frequency associated with more negative Xrs (and thus with an increase in resonant frequency). This probably also applies to patients with more advanced airways obstruction. The addition of the FEV1 values to the analysis provides only a small amount of independent information. The forced oscillation technique thus appears to be a sensitive tool to separate healthy subjects (smokers and nonsmokers) from patients with respiratory complaints associated or not with a reduced FEV1. PMID:6822104

  11. Percutaneous Transtracheal Jet Ventilation with Various Upper Airway Obstruction

    PubMed Central

    Doi, Tomoki; Miyashita, Tetsuya; Furuya, Ryousuke; Sato, Hitoshi; Takaki, Shunsuke; Goto, Takahisa

    2015-01-01

    A “cannot-ventilate, cannot-intubate” situation is critical. In difficult airway management, transtracheal jet ventilation (TTJV) has been recommended as an invasive procedure, but specialized equipment is required. However, the influence of upper airway resistance (UAR) during TTJV has not been clarified. The aim of this study was to compare TTJV using a manual jet ventilator (MJV) and the oxygen flush device of the anesthetic machine (AM). We made a model lung offering variable UAR by adjustment of tracheal tube size that can ventilate through a 14-G cannula. We measured side flow due to the Venturi effect during TTJV, inspired tidal volume (TVi), and expiratory time under various inspiratory times. No Venturi effect was detected during TTJV with either device. With the MJV, TVi tended to increase in proportion to UAR. With AM, significant variations in TVi was not detected with changes in any UAR. In conclusion, UAR influenced forward flow of TTJV in the model lung. The influence of choked flow from the Venturi effect was minimal under all UAR settings with the MJV, but the AM could not deliver sufficient flow. PMID:26161402

  12. Prenatal diagnosis of congenital high airway obstruction syndrome (CHAOS). Five case report.

    PubMed

    Aslan, Halil; Ekiz, Ali; Acar, Deniz Kanber; Aydiner, Burchan; Kaya, Basak; Sezer, Salim

    2015-03-01

    Congenital high airway obstruction syndrome (CHAOS) is an extremely rare life-threatening condition. Laryngeal atresia appears to be the most frequent cause. Generally the diagnosis is made with severely enlarged and highly echogenic lungs and additional ultrasound findings. The prognosis of the affected infants is often poor. Five cases are reported here that were diagnosed in a tertiary center between 2008 and 2014. PMID:25745665

  13. New Approaches to Positive Airway Pressure Treatment in Obstructive Sleep Apnea.

    PubMed

    Kuźniar, Tomasz J

    2016-06-01

    Continuous positive airway pressure (CPAP) is a mainstay of therapy in patients with obstructive sleep apnea (OSA). This technology has gone through tremendous changes that resulted in devices that can recognize and differentiate sleep-disordered breathing events, adjust their output to these events, monitor usage, and communicate with the treatment team. This article discusses recent developments in treatment of OSA with PAP. PMID:27236053

  14. Flat trachea syndrome: a rare condition with symptoms similar to obstructive airway disease.

    PubMed

    Gani, Mohammed Akil D; Rogers, Vanessa J C; Sachak, Khalid H; Marzouk, Joseph F K

    2015-01-01

    Flat trachea syndrome, commonly known as 'tracheobronchomalacia', is a central airway disease characterised by excessive expiratory collapse of the tracheobronchial posterior membrane due to weakness in the airway walls. Patients present with symptoms such as chronic cough, dyspnoea and recurrent respiratory tract infections, which are often attributed to more common conditions such as asthma and chronic obstructive pulmonary disease (COPD). The term 'Flat Trachea Syndrome' was first proposed by Niranjan and Marzouk in 2010 following a retrospective study of 28 patients with the condition who underwent surgery for it. The authors advocated the term due to the primary abnormality being collapse of the posterior membranous wall of the central airways as opposed to softening of the tracheal cartilage (tracheobronchomalacia), which they proposed is a misnomer. We present a rare case of a patient with flat trachea syndrome on a history of COPD who initially presented with recurrent respiratory tract infections. PMID:25721828

  15. Rigid bronchoscopy and silicone stents in the management of central airway obstruction

    PubMed Central

    Yarmus, Lonny

    2015-01-01

    The field of interventional pulmonology has grown significantly over the past several decades now including the diagnosis and therapeutic treatment of complex airway disease. Rigid bronchoscopy is an invaluable tool in the diagnosis and management of several malignant and non-malignant causes of central airway obstruction (CAO) and has become integral after the inception of airway stenting. The management of CAO can be a complicated endeavor with significant risks making the understanding of basic rigid bronchoscopy techniques, ablative technologies, anesthetic care and stenting of utmost importance in the care of these complex patients. This review article will focus on the history of rigid bronchoscopy, the technical aspects of performing a rigid bronchoscopy as well as the use of silicone stents their indications, complications and placement techniques. PMID:26807283

  16. Lung perfusion impairments in pulmonary embolic and airway obstruction with noncontrast MR imaging.

    PubMed

    Suga, Kazuyoshi; Ogasawara, Nobuhiko; Okada, Munemasa; Tsukuda, Toshinobu; Matsunaga, Naofumi; Miyazaki, Mitsue

    2002-06-01

    A noncontrast electrocardiography (ECG)-gated, fast-spin-echo magnetic resonance imaging was applied to noninvasively define perfusion impairments in pulmonary embolic and airway obstruction dog models. Two-phase ECG-gated lung images of the minimal lung signal intensity during systole and maximal signal intensity during diastole were acquired by using optimized R-wave triggering delay times in seven dogs anesthetized with pentobarbital sodium before, soon after, and 2 mo after embolization with enbucrilate and in another eight dogs before and after bronchial occlusion with balloon catheters, in combination with a gadolinium diethylenetriaminepentaacetic acid-enhanced dynamic study. An ECG-gated subtraction image between the two-phase lung images provided a uniform but gravity-dependent perfusion map in normal lungs. Furthermore, it defined all 13 variable-size perfusion deficits associated with pulmonary embolism and the dynamically decreased perfusion with time after bronchial occlusion in all the airway obstruction models. These results were consistent with contrast-enhanced pulmonary arterial perfusion phase images. This noncontrast imaging could be equivalent to a contrast-enhanced dynamic study in the definition of regionally impaired pulmonary arterial perfusion in pulmonary embolism and airway obstruction. PMID:12015358

  17. Interventional pulmonology techniques for immediate desobstruction of malignant central airway obstruction.

    PubMed

    Zarić, B; Canak, V; Sarcev, T; Marković, M; Jovanović, S; Budisin, E

    2007-01-01

    In recent years interventional pulmonology techniques have found their place in the palliative treatment of lung cancer invading central airways (trachea and principal bronchi). The curative effect of interventional techniques is reported in a number of studies with very different success ratios, but with excellent potential and perspective. Increase in number and variety of these techniques led to the development of internationally accepted guidelines for their use. The choice of a specific interventional technique in the treatment of lung cancer patients with central airway obstruction (CAO) depends on several factors: patient's general condition and comorbidities, type and characteristics of airway stenosis, availability of techniques and trained personnel. The aim of this review was to introduce interventional pulmonology procedures aimed at urgent desobstruction of central airways obstruction to medical oncologists who are dealing with the problem of malignant CAO. We tried to emphasize indications, contraindications, technique procedure and possible complications in the treatment of malignant CAO. At the Institute for Pulmonary Diseases of Vojvodina Nd: YAG laser resection, electrocautery, argon plasma coagulation and metallic and silicone stent insertions for immediate treatment of malignant CAO are practised. PMID:17436396

  18. The role of the small airways in the pathophysiology of asthma and chronic obstructive pulmonary disease.

    PubMed

    Bonini, Matteo; Usmani, Omar S

    2015-12-01

    Chronic respiratory diseases, such as asthma and chronic obstructive pulmonary disease (COPD), represent a major social and economic burden for worldwide health systems. During recent years, increasing attention has been directed to the role of small airways in respiratory diseases, and their exact contribution to the pathophysiology of asthma and COPD continues to be clarified. Indeed, it has been suggested that small airways play a distinct role in specific disease phenotypes. Besides providing information on small airways structure and diagnostic procedures, this review therefore aims to present updated and evidence-based findings on the role of small airways in the pathophysiology of asthma and COPD. Most of the available information derives from either pathological studies or review articles and there are few data on the natural history of small airways disease in the onset or progression of asthma and COPD. Comparisons between studies on the role of small airways are hard to draw because both asthma and COPD are highly heterogeneous conditions. Most studies have been performed in small population samples, and different techniques to characterize aspects of small airways function have been employed in order to assess inflammation and remodelling. Most methods of assessing small airways dysfunction have been largely confined to research purposes, but some data are encouraging, supporting the utilization of certain techniques into daily clinical practice, particularly for early-stage diseases, when subjects are often asymptomatic and routine pulmonary function tests may be within normal ranges. In this context further clinical trials and real-life feedback on large populations are desirable. PMID:26037949

  19. [Airway rescue in a patient with severe obstructive sleep apnea syndrome and impossible ventilation after induction of general anesthesia].

    PubMed

    Komasawa, Nobuyasu; Kusunoki, Tomohiro; Soen, Masako; Minami, Toshiaki

    2014-06-01

    We report the successful rescue ventilation of a patient with severe obstructive sleep apnea syndrome after induction of general anesthesia using the i-gel supraglottic airway device. A 55-year-old man was scheduled for resection of a cerebellopontine angle tumor. He suffered from severe obstructive sleep apnea syndrome and routinely used continuous positive airway pressure. His apnea hypopnea index was 57.8. Manual assisted ventilation following propofol and fentanyl administration was successful. On rocuronium administration, manual ventilation became impossible and oropharyngeal airway could not release this condition. We immediately inserted the i-gel device to provide sufficient ventilation. As tracheal intubation with the i-gel device was difficult, we intubated a spiral tube (internal diameter, 8.0 mm) using the Pentax-AWS Airwayscope. Our findings suggest that the i-gel device may be useful for emergent airway rescue in the event of impossible ventilation for patients with severe obstructive sleep apnea syndrome. PMID:24979854

  20. Oropharyngeal Dermoid Cyst in an Infant with Intermittent Airway Obstruction

    PubMed Central

    Wagner, Matthias W.; Haileselassie, Bereketeab; Kannan, Sujatha; Chen, Cynthia; Poretti, Andrea; Tunkel, David E.; Huisman, Thierry A.G.M.

    2014-01-01

    Summary Dermoid cysts are benign epithelial inclusions and cystic lesions that may occur in several locations including the oropharynx. We describe the case of a two-month-old baby girl who presented with progressive respiratory distress, hypoxemia, and feeding difficulties because of an oropharyngeal dermoid cyst. The child had an airway work-up that included laryngoscopy. However, the mass remained undetected. This is most likely explained by the mobile nature of the lesion, prolapsing into the high nasopharynx in supine position. In our patient, magnetic resonance imaging (MRI), initially performed to rule out brainstem pathology, revealed an oropharyngeal dermoid cyst. This case shows the potential role of neuroimaging in the diagnostic work-up of a young child presenting with respiratory distress by excluding a central nervous system lesion and diagnosing an “unexpected” nasopharyngeal mass lesion. In addition, MRI allowed exclusion of skull base lesions of neural origin such as an anterior meningoencephalocele or heterotopic neuroglial tissue which would be managed differently from pharyngeal masses. PMID:25260210

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

    PubMed Central

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

    2013-01-01

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

  2. Upper Airway Collapsibility During REM Sleep in Children with the Obstructive Sleep Apnea Syndrome

    PubMed Central

    Huang, Jingtao; Karamessinis, Laurie R.; Pepe, Michelle E.; Glinka, Stephen M.; Samuel, John M.; Gallagher, Paul R.; Marcus, Carole L.

    2009-01-01

    Study Objectives: In children, most obstructive events occur during rapid eye movement (REM) sleep. We hypothesized that children with the obstructive sleep apnea syndrome (OSAS), in contrast to age-matched control subjects, would not maintain airflow in the face of an upper airway inspiratory pressure drop during REM sleep. Design: During slow wave sleep (SWS) and REM sleep, we measured airflow, inspiratory time, inspiratory time/total respiratory cycle time, respiratory rate, tidal volume, and minute ventilation at a holding pressure at which flow limitation occurred and at 5 cm H2O below the holding pressure in children with OSAS and in control subjects. Setting: Sleep laboratory. Participants: Fourteen children with OSAS and 23 normal control subjects. Results: In both sleep states, control subjects were able to maintain airflow, whereas subjects with OSAS preserved airflow in SWS but had a significant decrease in airflow during REM sleep (change in airflow of 18.58 ± 12.41 mL/s for control subjects vs −44.33 ± 14.09 mL/s for children with OSAS, P = 0.002). Although tidal volume decreased, patients with OSAS were able to maintain minute ventilation by increasing the respiratory rate and also had an increase in inspiratory time and inspiratory time per total respiratory cycle time Conclusion: Children with OSAS do not maintain airflow in the face of upper-airway inspiratory-pressure drops during REM sleep, indicating a more collapsible upper airway, compared with that of control subjects during REM sleep. However, compensatory mechanisms exist to maintain minute ventilation. Local reflexes, central control mechanisms, or both reflexes and control mechanisms need to be further explored to better understand the pathophysiology of this abnormality and the compensation mechanism. Citation: Huang J; Karamessinis LR; Pepe ME; Glinka SM; Samuel JM; Gallagher PR; Marcus CL. Upper airway collapsibility during REM sleep in children with the obstructive sleep apnea

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

    SciTech Connect

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

    2013-10-01

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

  4. Comparison of NHANES III and ERS/GLI 12 for airway obstruction classification and severity.

    PubMed

    Linares-Perdomo, Olinto; Hegewald, Matthew; Collingridge, Dave S; Blagev, Denitza; Jensen, Robert L; Hankinson, John; Morris, Alan H

    2016-07-01

    The diagnosis and severity categorisation of obstructive lung disease is determined using reference values. The American Thoracic Society/European Respiratory Society in 2005 recommended the National Health and Nutrition Examination Survey (NHANES) III spirometry prediction equations for patients in USA aged 8-80 years. The Global Lung Initiative 2012 (GLI 12) provided spirometry prediction equations for patients aged 3-95 years. Comparison of the NHANES III and GLI 12 prediction equations for diagnosing and categorising airway obstruction in patients in USA has not been made.We aimed to quantify the differences between NHANES III and GLI 12 predicted values in Caucasians aged 18-95 years, using both mathematical simulation and clinical data. We compared predicted forced expiratory volume in 1 s (FEV1) and lower limit of normal (LLN) FEV1/forced vital capacity (FVC) % for NHANES III and GLI 12 prediction equations by applying both a simulation model and clinical spirometry data to quantify differences in the diagnosis and categorisation of airway obstruction.Mathematical simulation revealed significant similarities and differences between prediction equations for both LLN FEV1/FVC % and predicted FEV1 There are significant differences when using GLI 12 and NHANES III to diagnose airway obstruction and severity in Caucasian patients aged 18-95 years.Similarities and differences exist between NHANES III and GLI 12 for some age and height combinations. The differences in LLN FEV1/FVC % and predicted FEV1 are most prominent in older taller/shorter individuals. The magnitude of the differences can be large and may result in differences in clinical management. PMID:27288032

  5. Effects of cessation of terbutaline treatment on airway obstruction and responsiveness in patients with chronic obstructive pulmonary disease.

    PubMed Central

    de Jong, J. W.; Koëter, G. H.; van der Mark, T. W.; Postma, D. S.

    1996-01-01

    BACKGROUND: Cessation of regular therapy with inhaled beta 2 agonists in patients with asthma may lead to a temporary deterioration of lung function and airway responsiveness. Few such studies have been reported in patients with chronic obstructive pulmonary disease (COPD), so an investigation was carried out to determine whether rebound airway responsiveness and rebound bronchoconstriction also occurs in COPD and if there is any relationship with the dose of beta 2 agonist being used. METHODS: Lung function (forced expiratory volume in one second (FEV1) and peak expiratory flow (PEF)), airway responsiveness (PC20 methacholine (PC20)) and symptoms were assessed in a double blind, placebo controlled crossover study during and after cessation of two weeks regular treatment with placebo, and low dose (250 micrograms) and high dose (1000 micrograms) inhaled terbutaline via a dry powder inhaler (Turbohaler) all given three times a day. Sixteen non-allergic patients with COPD of mean (SD) age 58.7 (6.5) years, FEV1 57.1 (12.8)% of predicted, and reversibility on 1000 micrograms terbutaline of 4.5 (3.5)% predicted were studied. PC20 and FEV1 were measured 10, 14, 34 and 82 hours after the last inhalation of terbutaline or placebo. Measurements performed at 10, 14, and 34 hours were expressed relative to 82 hour values in each period, transformed into an area under the curve (AUC) value and analysed by ANOVA. RESULTS: Mean morning and evening PEF increased during terbutaline treatment. PC20 and FEV1 did not change after cessation of terbutaline treatment. CONCLUSIONS: Cessation of regular treatment with both low and high dose inhaled terbutaline does not result in a rebound bronchoconstriction and rebound airway responsiveness in patients with COPD. PMID:8882073

  6. Differential Gene Expression Profiles and Selected Cytokine Protein Analysis of Mediastinal Lymph Nodes of Horses with Chronic Recurrent Airway Obstruction (RAO) Support an Interleukin-17 Immune Response

    PubMed Central

    2015-01-01

    Recurrent airway obstruction (RAO) is a pulmonary inflammatory condition that afflicts certain mature horses exposed to organic dust particulates in hay. Its clinical and pathological features, manifested by reversible bronchoconstriction, excessive mucus production and airway neutrophilia, resemble the pulmonary alterations that occur in agricultural workers with occupational asthma. The immunological basis of RAO remains uncertain although its chronicity, its localization to a mucosal surface and its domination by a neutrophilic, non-septic inflammatory response, suggest involvement of Interleukin-17 (IL-17). We examined global gene expression profiles in mediastinal (pulmonary-draining) lymph nodes isolated from RAO-affected and control horses. Differential expression of > 200 genes, coupled with network analysis, supports an IL-17 response centered about NF-κB. Immunohistochemical analysis of mediastinal lymph node sections demonstrated increased IL-17 staining intensity in diseased horses. This result, along with the finding of increased IL-17 concentrations in lymph node homogenates from RAO-affected horses (P = 0.1) and a down-regulation of IL-4 gene and protein expression, provides additional evidence of the involvement of IL-17 in the chronic stages of RAO. Additional investigations are needed to ascertain the cellular source of IL-17 in this equine model of occupational asthma. Understanding the immunopathogenesis of this disorder likely will enhance the development of therapeutic interventions beneficial to human and animal pulmonary health. PMID:26561853

  7. Pharyngolaryngeal location of Kaposi's sarcoma with airway obstruction in an HIV-negative patient.

    PubMed

    Torretta, Sara; Gaffuri, Michele; Recalcati, Sebastiano; Marzano, Angelo Valerio; Cantarella, Giovanna; Iofrida, Elisabetta; Pignataro, Lorenzo

    2013-01-01

    Kaposi's sarcoma (KS) is a human herpes virus-8 (HHV-8)-associated angioproliferative disorder, and its occurrence may be favored by human immunodeficiency virus (HIV) infection and iatrogenic immunosuppression. It has also been postulated that a chronic inflammatory disease of the skin can pave the way to its development. KS generally involves mucosal and cutaneous sites, including the head and neck. An oropharyngeal location is quite common, but laryngeal involvement with possible upper airway obstruction and respiratory distress requiring tracheotomy is rare, and no hypopharyngeal locations have yet been reported. We describe the case of a 68-year-old male patient who developed KS after immunosuppressive treatment for pemphigus vulgaris, an autoimmune bullous disease presenting with blisters and erosions on the skin and the oral mucosa. KS was initially localized to the oral cavity and oropharynx, but subsequent involvement of the laryngeal and hypopharyngeal tract led to acute airway obstruction and the need for tracheotomy. This unique case of pharyngolaryngeal KS suggests that clinicians faced with purple nodular lesions should consider a differential diagnosis of KS in immunocompromised patients, even if they are HIV negative, and should carefully manage the patency of the upper airways. PMID:24362871

  8. Citric acid cough threshold and airway responsiveness in asthmatic patients and smokers with chronic airflow obstruction.

    PubMed Central

    Auffarth, B; de Monchy, J G; van der Mark, T W; Postma, D S; Koëter, G H

    1991-01-01

    The relation between citric acid cough threshold and airway hyperresponsiveness was investigated in 11 non-smoking patients with allergic asthma (mean FEV1 94% predicted) and 25 non-atopic smokers with chronic airflow obstruction (mean FEV1 65% predicted). Cough threshold was determined on two occasions by administering doubling concentrations of citric acid. Seven of the 11 asthmatic subjects and 14 of 25 smokers with chronic airflow obstruction had a positive cough threshold on both test days. Cough threshold measurements were reproducible in both groups (standard deviation of duplicate measurements 1.2 doubling concentrations in asthma, 1.1 doubling concentrations in chronic airflow obstruction). Citric acid provocation did not cause bronchial obstruction in most patients, though four patients had a fall in FEV1 of more than 20% for a short time on one occasion only. No significant difference in cough threshold was found between the two patient groups despite differences in baseline FEV1 values. There was no significant correlation between cough threshold and the provocative concentration of histamine causing a 20% fall in FEV1 (PC20) histamine in either group. Thus sensory nerves can be activated with a tussive agent in patients with asthma and chronic airflow obstruction without causing bronchial smooth muscle contraction. PMID:1948792

  9. Blockage of upper airway

    MedlinePlus

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

  10. Analysis of the interplay between neurochemical control of respiration and upper airway mechanics producing upper airway obstruction during sleep in humans.

    PubMed

    Longobardo, G S; Evangelisti, C J; Cherniack, N S

    2008-02-01

    Increased loop gain (a function of both controller gain and plant gain), which results in instability in feedback control, is of major importance in producing recurrent central apnoeas during sleep but its role in causing obstructive apnoeas is not clear. The purpose of this study was to investigate the role of loop gain in producing obstructive sleep apnoeas. Owing to the complexity of factors that may operate to produce obstruction during sleep, we used a mathematical model to sort them out. The model used was based on our previous model of neurochemical control of breathing, which included the effects of chemical stimuli and changes in alertness on respiratory pattern generator activity. To this we added a model of the upper airways that contained a narrowed section which behaved as a compressible elastic tube and was tethered during inspiration by the contraction of the upper airway dilator muscles. These muscles in the model, as in life, responded to changes in hypoxia, hypercapnia and alertness in a manner similar to the action of the chest wall muscles, opposing the compressive action caused by the negative intraluminal pressure generated during inspiration which was magnified by the Bernoulli Effect. As the velocity of inspiratory airflow increased, with sufficiently large increase in airflow velocity, obstruction occurred. Changes in breathing after sleep onset were simulated. The simulations showed that increases in controller gain caused the more rapid onset of obstructive apnoeas. Apnoea episodes were terminated by arousal. With a constant controller gain, as stiffness decreased, obstructed breaths appeared and periods of obstruction recurred longer after sleep onset before disappearing. Decreased controller gain produced, for example, by breathing oxygen eliminated the obstructive apnoeas resulting from moderate reductions in constricted segment stiffness. This became less effective as stiffness was reduced more. Contraction of the upper airway muscles

  11. Use of modified barium swallow study to measure posterior airway space in obstructive sleep apnea.

    PubMed

    Crosby, Tyler; Phillips, Jeff; Carbo, Alberto; Babcock, Kelley; Nathan, Cherie-Ann

    2016-06-01

    Conclusion Measurement of the posterior airway space (PAS) using modified barium swallow (MBS) appears to correlate well with CT imaging. This data suggests MBS may be a low-cost alternative imaging modality to assess obstructive sleep apnea patients. Objectives Obstructive sleep apnea research has focused on imaging modalities that supplement polysomnography in evaluation of potential sites of airway obstruction. While several techniques have been used to assess the PAS, many incur significant costs and risks to the patient. This study proposes use of MBS as a simple modality to measure PAS. Advantages include its simplicity, lower radiation, and dynamic tongue base visualization, which may help predict surgical outcomes. It is hypothesized that cephalometric measurements obtained using MBS will correlate well with CT. Methods Thirty-six adult patients who underwent both CT imaging and MBS for head and neck cancer were included. Cephalometric measurements of the PAS were obtained using each imaging modality. Statistical analysis focused on correlating measurements taken using CT and MBS. Results The average PAS measurements were 12.53 ± 1.81 mm and 12.80 ± 1.75 mm by MBS and CT imaging, respectively. In comparing the two modalities, Pearson correlation between CT and MBS measurements revealed significant positive correlations between r = 0.769 and 0.937. PMID:26852777

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

    PubMed Central

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

    2013-01-01

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

  13. Effect of Continuous Positive Airway Pressure on Airway Inflammation and Oxidative Stress in Patients with Obstructive Sleep Apnea

    PubMed Central

    Tichanon, Promsrisuk; Sopida, Santamit; Orapin, Pasurivong; Watchara, Boonsawat; Banjamas, Intarapoka

    2016-01-01

    Background. Airway inflammation and oxidative stress may be linked in obstructive sleep apnea (OSA) patients. We determined the effectiveness of continuous positive airway pressure (CPAP) therapy in reducing fractional exhaled nitric oxide (FeNO) and malondialdehyde (MDA) levels in OSA patients. Methods. Thirteen patients with OSA and 13 normal controls were recruited. FeNO and MDA levels were measured in the controls and in OSA patients before and after three months of CPAP therapy. Results. FeNO and MDA levels were higher in the patients compared to the age and gender matched controls (FeNO: 25.9 ± 5.0 versus 17.5 ± 5.9 ppb, P < 0.001; MDA: 14.6 ± 7.8 versus 2.1 ± 0.3 μmol/L, P < 0.001). FeNO and MDA levels were lower post-CPAP compared to pre-CPAP (FeNO: 25.9 ± 5.0 versus 17.0 ± 2.3 ppb, P < 0.001; MDA: 14.6 ± 7.8 versus 10.0 ± 6.4 μmol/L, P < 0.01). Apnea-hypopnea index (15.9 ± 6.6 versus 4.1 ± 2.1/h, P < 0.001) and mean arterial pressure (P < 0.01) decreased following CPAP treatment. Daytime mean SpO2 (P < 0.05) increased. Conclusion. Our study demonstrates that CPAP therapy yields clinical benefits by reducing upper airway inflammation and oxidative stress in OSA patients. PMID:27445526

  14. Tracheobronchomalacia/excessive dynamic airway collapse in patients with chronic obstructive pulmonary disease with persistent expiratory wheeze: A pilot study

    PubMed Central

    Sindhwani, Girish; Sodhi, Rakhee; Saini, Manju; Jethani, Varuna; Khanduri, Sushant; Singh, Baltej

    2016-01-01

    Background: Tracheobronchomalacia (TBM) refers to a condition in which structural integrity of cartilaginous wall of trachea is lost. Excessive dynamic airway collapse (EDAC) is characterized by excessive invagination of posterior wall of trachea. In both these conditions, airway lumen gets compromised, especially during expiration, which can lead to symptoms such as breathlessness, cough, and wheezing. Both these conditions can be present in obstructive lung diseases; TBM due to chronic airway inflammation and EDAC due to dynamic compressive forces during expiration. The present study was planned with the hypothesis that TBM/EDAC could also produce expiratory wheeze in patients with obstructive airway disorders. Hence, prevalence and factors affecting presence of this entity in patients with obstructive airway diseases were the aims and objectives of this study. Materials and Methods: Twenty-five patients with obstructive airway disorders (chronic obstructive pulmonary disease [COPD] or bronchial asthma), who were stable on medical management, but having persistent expiratory wheezing, were included in the study. They were evaluated for TBM/EDAC by bronchoscopy and computed tomographic scan of chest. The presence of TBM/EDAC was correlated with variables including age, sex, body mass index (BMI), smoking index, level of dyspnea, and severity of disease. Results: Mean age of the patients was 62.7 ± 7.81 years. Out of 25 patients, 14 were males. TBM/EDAC was found in 40% of study subjects. Age, sex, BMI, severity of disease, frequency of exacerbations and radiological findings etc., were not found to have any association with presence of TBM/EDAC. Conclusion: TBM/EDAC is common in patients with obstructive airway disorders and should be evaluated in these patients, especially with persistent expiratory wheezing as diagnosis of this entity could provide another treatment option in these patients with persistent symptoms despite medical management. PMID:27578929

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

    PubMed Central

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

    2016-01-01

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

  16. [Intraoperative acute airway obstruction due to the damage of a reinforced endotracheal tube in thyroidectomy].

    PubMed

    Ida, Mitsuru; Kuzumoto, Naoya; Nakayama, Kana; Krimoto, Katsuhiro; Kamiya, Toru; Iwata, Masato; Shimomura, Toshiyuki

    2014-10-01

    A 55-year-old woman was scheduled for left thyroidectomy. Anesthesia was induced without problems and maintained without nitrous oxide. Sixteen minutes after the start of the procedure, airway pressures and endtidal carbon dioxide concentration increased suddenly. An attempt to pass a suction catheter down the endotracheal tube was unsuccessful. A protuberance was found in the reinforced endotracheal tube. After reintubation with a new reinforced endotracheal tube, ventilation was improved immediately. The rest of the procedure was done uneventfully. Similar phenomenon was reported in the reuse of endotracheal tube and the use of nitrous oxide. In our case, airway obstruction was caused by the pinhole that was created in a manufacturing process. We have to keep in mind that endotracheal tube itself may be out of order if other causes have been excluded. PMID:25693343

  17. New developments in the use of positive airway pressure for obstructive sleep apnea

    PubMed Central

    Boeder, Schafer; Malhotra, Atul; Patel, Sanjay R.

    2015-01-01

    Obstructive sleep apnea (OSA) is a disorder which afflicts a large number of individuals around the world. OSA causes sleepiness and is a major cardiovascular risk factor. Since its inception in the early 1980’s, continuous positive airway pressure (CPAP) has emerged as the major treatment of OSA, and it has been shown to improve sleepiness, hypertension, and a number of cardiovascular indices. Despite its successes, adherence with treatment remains a major limitation. Herein we will review the evidence behind the use of positive airway pressure (PAP) therapy, its various modes, and the methods employed to improve adherence. We will also discuss the future of PAP therapy in OSA and personalization of care. PMID:26380760

  18. Respiratory failure due to upper airway obstruction in children: use of the helmet as bridge interface.

    PubMed

    Racca, F; Cutrera, R; Robba, C; Caldarelli, V; Paglietti, M; De Angelis, M C; Sekhon, M S; Gualino, J; Bella, C; Passoni, N; Ranieri, V M

    2015-02-01

    Upper airway obstruction (UAO) can cause severe respiratory distress in young children by increasing inspiratory muscle load and decreasing alveolar ventilation, ultimately resulting in hypercapnia and hypoxemia which have long term negative cardiovascular effects. Although non-invasive continuous positive airway pressure (CPAP) improves gas exchange in these patients, use of conventional interfaces (nasal mask, nasal pillow and facial mask) may cause significant discomfort and lead to CPAP intolerance. We report five cases of children affected by UAO who experienced CPAP intolerance via application of conventional interfaces. Alternatively, we acutely applied helmet-CPAP which resulted in improved breathing pattern and gas exchange. Thereafter, patients received training with respect to a nasal CPAP interface, allowing successful long term treatment. In conclusion, these five clinical cases demonstrate that helmet-CPAP can be used acutely in children with UAO if compliance to conventional modalities is problematic, allowing for sufficient time to achieve compliance to nasal-CPAP. PMID:24918190

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

    NASA Astrophysics Data System (ADS)

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

    2014-03-01

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

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

    SciTech Connect

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

    2008-03-01

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

  1. Role of Orexin in Respiratory and Sleep Homeostasis during Upper Airway Obstruction in Rats

    PubMed Central

    Tarasiuk, Ariel; Levi, Avishag; Berdugo-Boura, Nilly; Yahalom, Ari; Segev, Yael

    2014-01-01

    Study Objectives: Chronic upper airway obstruction (UAO) elicits a cascade of complex endocrine derangements that affect growth, sleep, and energy metabolism. We hypothesized that elevated hypothalamic orexin has a role in maintaining ventilation during UAO, while at the same time altering sleep-wake activity and energy metabolism. Here, we sought to explore the UAO-induced changes in hypothalamic orexin and their role in sleep-wake balance, respiratory activity, and energy metabolism. Interventions: The tracheae of 22-day-old Sprague-Dawley rats were surgically narrowed; UAO and sham-operated control animals were monitored for 7 weeks. We measured food intake, body weight, temperature, locomotion, and sleep-wake activity. Magnetic resonance imaging was used to quantify subcutaneous and visceral fat tissue volumes. In week 7, the rats were sacrificed and levels of hypothalamic orexin, serum leptin, and corticosterone were determined. The effect of dual orexin receptor antagonist (almorexant 300 mg/kg) on sleep and respiration was also explored. Measurements and Results: UAO increased hypothalamic orexin mRNA and protein content by 64% and 65%, respectively. UAO led to 30% chronic sleep loss, excessive active phase sleepiness, decreased body temperature, increased food intake, reduction of abdominal and subcutaneous fat tissue volume, and growth retardation. Administration of almorexant normalized sleep but induced severe breathing difficulties in UAO rats, while it had no effect on sleep or on breathing of control animals. Conclusions: In upper airway obstruction animals, enhanced orexin secretion, while crucially important for respiratory homeostasis maintenance, is also responsible for chronic partial sleep loss, as well as considerable impairment of energy metabolism and growth. Citation: Tarasiuk A, Levi A, Berdugo-Boura N, Yahalom A, Segev Y. Role of orexin in respiratory and sleep homeostasis during upper airway obstruction in rats. SLEEP 2014

  2. Supramolecular Dynamics of Mucus

    PubMed Central

    Verdugo, Pedro

    2012-01-01

    Our purpose here is not to address specific issues of mucus pathology, but to illustrate how polymer networks theory and its remarkable predictive power can be applied to study the supramolecular dynamics of mucus. Avoiding unnecessary mathematical formalization, in the light of available theory, we focus on the rather slow progress and the still large number of missing gaps in the complex topology and supramolecular dynamics of airway mucus. We start with the limited information on the polymer physics of respiratory mucins to then converge on the supramolecular organization and resulting physical properties of the mucus gel. In each section, we briefly discuss progress on the subject, the uncertainties associated with the established knowledge, and the many riddles that still remain. PMID:23125200

  3. Selective indication for positive airway pressure (PAP) in sleep-related breathing disorders with obstruction

    PubMed Central

    Stasche, Norbert

    2006-01-01

    Positive airway pressure (PAP) is the therapy of choice for most sleep-related breathing disorders (SRBD). A variety of PAP devices using positive airway pressure (CPAP, BiPAP, APAP, ASV) must be carefully considered before application. This overview aims to provide criteria for choosing the optimal PAP device according to severity and type of sleep-related breathing disorder. In addition, the range of therapeutic applications, constraints and side effects as well as alternative methods to PAP will be discussed. This review is based on an analysis of current literature and clinical experience. The data is presented from an ENT-sleep-laboratory perspective and is designed to help the ENT practitioner initiate treatment and provide support. Different titration methods, current devices and possible applications will be described. In addition to constant pressure devices (CPAP), most commonly used for symptomatic obstructive sleep apnoea (OSA) without complicating conditions, BiPAP models will be introduced. These allow two different positive pressure settings and are thus especially suitable for patients with cardiopulmonary diseases or patients with pressure intolerance, increasing compliance in this subgroup considerably. Compliance can also be increased in patients during first night of therapy, patients with highly variable pressure demands or position-dependent OSA, by using self-regulating Auto-adjust PAP devices (Automatic positive airway pressure, APAP). Patients with Cheyne-Stokes breathing, a subtype of central sleep apnoea, benefit from adaptive servo-ventilation (ASV), which analyzes breathing patterns continually and adjusts the actual ventilation pressure accordingly. This not only reduces daytime sleepiness, but can also influence heart disease positively. Therapy with positive airway pressure is very effective in eliminating obstruction-related sleep diseases and symptoms. However, because therapy is generally applied for life, the optimal PAP device

  4. Practice Parameters for the Surgical Modifications of the Upper Airway for Obstructive Sleep Apnea in Adults

    PubMed Central

    Aurora, R. Nisha; Casey, Kenneth R.; Kristo, David; Auerbach, Sanford; Bista, Sabin R.; Chowdhuri, Susmita; Karippot, Anoop; Lamm, Carin; Ramar, Kannan; Zak, Rochelle; Morgenthaler, Timothy I.

    2010-01-01

    Background: Practice parameters for the treatment of obstructive sleep apnea syndrome (OSAS) in adults by surgical modification of the upper airway were first published in 1996 by the American Academy of Sleep Medicine (formerly ASDA). The following practice parameters update the previous practice parameters. These recommendations were reviewed and approved by the Board of Directors of the American Academy of Sleep Medicine. Methods: A systematic review of the literature was performed, and the GRADE system was used to assess the quality of evidence. The findings from this evaluation are provided in the accompanying review paper, and the subsequent recommendations have been developed from this review. The following procedures have been included: tracheostomy, maxillo-mandibular advancement (MMA), laser assisted uvulopalatoplasty (LAUP), uvulopalatopharyngoplasty (UPPP),radiofrequency ablation (RFA), and palatal implants. Recommendations: The presence and severity of obstructive sleep apnea must be determined before initiating surgical therapy (Standard). The patient should be advised about potential surgical success rates and complications, the availability of alternative treatment options such as nasal positive airway pressure and oral appliances, and the levels of effectiveness and success rates of these alternative treatments (Standard). The desired outcomes of treatment include resolution of the clinical signs and symptoms of obstructive sleep apnea and the normalization of sleep quality, the apnea-hypopnea index, and oxyhemoglobin saturation levels (Standard). Tracheostomy has been shown to be an effective single intervention to treat obstructive sleep apnea. This operation should be considered only when other options do not exist, have failed, are refused, or when this operation is deemed necessary by clinical urgency (Option). MMA is indicated for surgical treatment of severe OSA in patients who cannot tolerate or who are unwilling to adhere to positive

  5. Multidisciplinary correction of anterior open bite relapse and upper airway obstruction

    PubMed Central

    Perri, Alessandro; Siviero, Laura; Bonetti, Giulio Alessandri; Cocilovo, Francesco; Stellini, Edoardo

    2015-01-01

    A 27-year-old man presented an anterior open bite relapse. He had low tongue posture positioned anteriorly at rest and during swallowing and reported chronic difficulty in nose breathing. Head cone-beam computed tomography revealed nasal septum deviation, right turbinate hypertrophy, and left maxillary sinus congestion, which were thought to contribute to the breathing problem, encourage the improper tongue posture, and thereby cause the relapse. Multidisciplinary treatment involving an otorhinolaryngologist, an orthodontist, and a periodontist resolved the upper airway obstruction and corrected the malocclusion. The follow-up examination after 3 years 5 months demonstrated stable results. PMID:25667917

  6. Dental implant removal to facilitate suspension laryngoscopy and laser treatment of an obstructed airway.

    PubMed

    Hume-Smith, H; Fowler, A; Vaz, F; Suaris, P

    2010-01-01

    A 29-year-old patient presented with dysphonia, dysphagia and a progressive history of stridor over 6 weeks. His past medical history included childhood nasolabial rhabdomyosarcoma treated by surgery, chemotherapy and radiotherapy. This had resulted in marked abnormalities of the facial skeleton, limited neck extension and restricted mouth opening of 1 cm, in part due to dental implants. After careful discussion and planning within a multidisciplinary team, the airway was optimised by temporary removal of the dental implants. This enabled a suspension laryngoscope to be passed, permitting carbon dioxide laser treatment to an obstruction at the laryngeal inlet and eliminating the need for a tracheostomy. PMID:19849679

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

    PubMed

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

    2016-09-01

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

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

    PubMed

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

    1995-04-01

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

  9. Occupational obstructive airway diseases in Germany: Frequency and causes in an international comparison

    SciTech Connect

    Latza, U.; Baur, X.

    2005-08-01

    Occupational inhalative exposures contribute to a significant proportion of obstructive airway diseases (OAD), namely chronic obstructive pulmonary disease (COPD) and asthma. The number of occupational OAD in the German industrial sector for the year 2003 are presented. Other analyses of surveillance data were retrieved from Medline. Most confirmed reports of OAD are cases of sensitizer induced occupational asthma (625 confirmed cases) followed by COPD in coal miners (414 cases), irritant induced occupational asthma (156 cases), and isocyanate asthma (54 cases). Main causes of occupational asthma in Germany comprise flour/flour constituents (35.9%), food/feed dust (9.0%), and isocyanates (6.5%). Flour and grain dust is a frequent cause of occupational asthma in most European countries and South Africa. Isocyanates are still a problem worldwide. Although wide differences in the estimated incidences between countries exist due to deficits in the coverage of occupational OAD, the high numbers necessitate improvement of preventive measures.

  10. [Experimental studies on cardiopulmonary relation under hypoxia, hypercapnia and airway obstruction in dog (author's transl)].

    PubMed

    Kowalski, J; Islam, M S; Bugalho de Almeida, A A; Ulmer, W T

    1980-01-01

    On 18 dogs the effects of hypoxia (12, 10, 7.5% O2) and hypoxia and hypercapnia (10% O2 + 5, 7.5, 11% CO2) on breathing, pulmonary vascular resistance, cardiac output and on the arterial and venous oxygen pressure were investigated. The relationship between arterial oxygen pressure to Pap as to vascular resistance is not in the mean linear. There are good, bad and nearly nonresponders in respect to the vascular resistance on the dogs. Therefore, calculation and evaluation of mean values are less helpful. A similar variation on men could help to understand also better the large scatter which is always shown on correlations between PO2a : Pap or PO2a : vascular resistance. Also the different pattern of the V/Q relationship may be influenced by the amount of the vascular response to local alveolar hypoxia. An increase of PCO/a potentiates the local vasoconstrictor effect of hypoxia. Mainly this was seen in the range between hypocapnia and moderate rates of hypercapnia. Hypoxia shows an increase of breathing frequency, hypercapnia shows and increase in tidal volume. Also under hypercapnia there are nonresponders and better responders in response to the vascular resistance in the lung circulation. Mechanical airway obstruction is followed by an increase of tidal volume; obstruction caused by acetylcholine is followed by a decrease of tidal volume and an increase of breathing frequency. Changes in the arterial blood gases are caused by changes in the ventilation perfusion relationship only under acetylcholine obstruction. Influences on the lung circulation by the airway obstruction under these experimental conditions as direct effects are small or not existent. PMID:7221190

  11. Airway Gland Structure and Function.

    PubMed

    Widdicombe, Jonathan H; Wine, Jeffrey J

    2015-10-01

    Submucosal glands contribute to airway surface liquid (ASL), a film that protects all airway surfaces. Glandular mucus comprises electrolytes, water, the gel-forming mucin MUC5B, and hundreds of different proteins with diverse protective functions. Gland volume per unit area of mucosal surface correlates positively with impaction rate of inhaled particles. In human main bronchi, the volume of the glands is ∼ 50 times that of surface goblet cells, but the glands diminish in size and frequency distally. ASL and its trapped particles are removed from the airways by mucociliary transport. Airway glands have a tubuloacinar structure, with a single terminal duct, a nonciliated collecting duct, then branching secretory tubules lined with mucous cells and ending in serous acini. They allow for a massive increase in numbers of mucus-producing cells without replacing surface ciliated cells. Active secretion of Cl(-) and HCO3 (-) by serous cells produces most of the fluid of gland secretions. Glands are densely innervated by tonically active, mutually excitatory airway intrinsic neurons. Most gland mucus is secreted constitutively in vivo, with large, transient increases produced by emergency reflex drive from the vagus. Elevations of [cAMP]i and [Ca(2+)]i coordinate electrolyte and macromolecular secretion and probably occur together for baseline activity in vivo, with cholinergic elevation of [Ca(2+)]i being mainly responsive for transient increases in secretion. Altered submucosal gland function contributes to the pathology of all obstructive diseases, but is an early stage of pathogenesis only in cystic fibrosis. PMID:26336032

  12. Effect of Nasal Obstruction on Continuous Positive Airway Pressure Treatment: Computational Fluid Dynamics Analyses

    PubMed Central

    Wakayama, Tadashi; Suzuki, Masaaki; Tanuma, Tadashi

    2016-01-01

    Objective Nasal obstruction is a common problem in continuous positive airway pressure (CPAP) therapy for obstructive sleep apnea and limits treatment compliance. The purpose of this study is to model the effects of nasal obstruction on airflow parameters under CPAP using computational fluid dynamics (CFD), and to clarify quantitatively the relation between airflow velocity and pressure loss coefficient in subjects with and without nasal obstruction. Methods We conducted an observational cross-sectional study of 16 Japanese adult subjects, of whom 9 had nasal obstruction and 7 did not (control group). Three-dimensional reconstructed models of the nasal cavity and nasopharynx with a CPAP mask fitted to the nostrils were created from each subject’s CT scans. The digital models were meshed with tetrahedral cells and stereolithography formats were created. CPAP airflow simulations were conducted using CFD software. Airflow streamlines and velocity contours in the nasal cavities and nasopharynx were compared between groups. Simulation models were confirmed to agree with actual measurements of nasal flow rate and with pressure and flow rate in the CPAP machine. Results Under 10 cmH2O CPAP, average maximum airflow velocity during inspiration was 17.6 ± 5.6 m/s in the nasal obstruction group but only 11.8 ± 1.4 m/s in the control group. The average pressure drop in the nasopharynx relative to inlet static pressure was 2.44 ± 1.41 cmH2O in the nasal obstruction group but only 1.17 ± 0.29 cmH2O in the control group. The nasal obstruction and control groups were clearly separated by a velocity threshold of 13.5 m/s, and pressure loss coefficient threshold of approximately 10.0. In contrast, there was no significant difference in expiratory pressure in the nasopharynx between the groups. Conclusion This is the first CFD analysis of the effect of nasal obstruction on CPAP treatment. A strong correlation between the inspiratory pressure loss coefficient and maximum airflow

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

    PubMed Central

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

    2016-01-01

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

  14. A Case of Spontaneous Postpartum Thyroid Hemorrhage Leading to Upper Airway Obstruction

    PubMed Central

    Hristov, Boris D.; Borrego, Robert; Harding, Patricia A.; Hristov, Dimiter B.

    2016-01-01

    Patient: Female, 36 Final Diagnosis: Thyroid hemorrhage Symptoms: Shortness of breath Medication: — Clinical Procedure: Thyroidectomy Specialty: Surgery Objective: Rare disease Background: Spontaneous goiter hemorrhage is a rare entity that can lead to life-threatening respiratory compromise. Goiter hemorrhages are usually due to effects of anticoagulation or neoplastic processes. The hormonal effects of pregnancy may also lead to such life-threatening goiter hemorrhages in the immediate postpartum period. Case Report: We report the case of a 36-year-old woman who complained of progressive neck swelling as well as eventual shortness of breath in the immediate postpartum period. Computed tomography scans and ultrasound of the neck revealed an enlarged and heterogenous thyroid with airway compression. The patient underwent an emergent subtotal thyroidectomy to alleviate the mass effect on the airway. Upon resection, the thyroid was noted to contain a goiter hemorrhage with no signs of neoplastic degeneration on pathology. Conclusions: Pregnancy is a known hormonal stressor that routinely increases the size of the thyroid and also predisposes patients to goiter formation. In rare cases, thyroid goiters may be predisposed to hemorrhage, causing airway obstruction and necessitating urgent surgical intervention. PMID:27012654

  15. Computational fluid dynamics simulation of the upper airway of obstructive sleep apnea syndrome by Muller maneuver.

    PubMed

    Nie, Ping; Xu, Xiao-Long; Tang, Yan-Mei; Wang, Xiao-Ling; Xue, Xiao-Chen; Wu, Ya-Dong; Zhu, Min

    2015-06-01

    This study aimed to use computer simulation to describe the fluid dynamic characteristics in patients with obstructive sleep apnea syndrome (OSAS) and to evaluate the difference between during quiet respiration and the Muller maneuver (MM). Seven patients with OSAS were involved to perform computed tomographic (CT) scanning during quiet respiration and the MM. CT data in DICOM format were transformed into an anatomically three-dimensional computational fluid dynamics (CFD) model of the upper airway. The velocity magnitude, relative pressure, and flow distribution were obtained. Numerical simulation of airflow was performed to discuss how the MM affected airflow in the upper airway. To measure the discrepancy, the SPSS19.0 software package was utilized for statistic analysis. The results showed that the shape of the upper airway became narrower, and the pressure decreased during the MM. The minimal cross-sectional area (MCSA) of velopharynx was significantly decreased (P<0.05) and the airflow velocity in MCSAs of velopharynx and glossopharynx significantly accelerated (P<0.05) during the MM. This study demonstrated the possibility of CFD model combined with the MM for understanding pharyngeal aerodynamics in the pathophysiology of OSAS. PMID:26072090

  16. Eosinophilic airway inflammation: role in asthma and chronic obstructive pulmonary disease

    PubMed Central

    George, Leena; Brightling, Christopher E.

    2016-01-01

    The chronic lung diseases, asthma and chronic obstructive pulmonary disease (COPD), are common affecting over 500 million people worldwide and causing substantial morbidity and mortality. Asthma is typically associated with Th2-mediated eosinophilic airway inflammation, in contrast to neutrophilic inflammation observed commonly in COPD. However, there is increasing evidence that the eosinophil might play an important role in 10–40% of patients with COPD. Consistently in both asthma and COPD a sputum eosinophilia is associated with a good response to corticosteroid therapy and tailored strategies aimed to normalize sputum eosinophils reduce exacerbation frequency and severity. Advances in our understanding of the multistep paradigm of eosinophil recruitment to the airway, and the consequence of eosinophilic inflammation, has led to the development of new therapies to target these molecular pathways. In this article we discuss the mechanisms of eosinophilic trafficking, the tools to assess eosinophilic airway inflammation in asthma and COPD during stable disease and exacerbations and review current and novel anti-eosinophilic treatments. PMID:26770668

  17. Eosinophilic airway inflammation: role in asthma and chronic obstructive pulmonary disease.

    PubMed

    George, Leena; Brightling, Christopher E

    2016-01-01

    The chronic lung diseases, asthma and chronic obstructive pulmonary disease (COPD), are common affecting over 500 million people worldwide and causing substantial morbidity and mortality. Asthma is typically associated with Th2-mediated eosinophilic airway inflammation, in contrast to neutrophilic inflammation observed commonly in COPD. However, there is increasing evidence that the eosinophil might play an important role in 10-40% of patients with COPD. Consistently in both asthma and COPD a sputum eosinophilia is associated with a good response to corticosteroid therapy and tailored strategies aimed to normalize sputum eosinophils reduce exacerbation frequency and severity. Advances in our understanding of the multistep paradigm of eosinophil recruitment to the airway, and the consequence of eosinophilic inflammation, has led to the development of new therapies to target these molecular pathways. In this article we discuss the mechanisms of eosinophilic trafficking, the tools to assess eosinophilic airway inflammation in asthma and COPD during stable disease and exacerbations and review current and novel anti-eosinophilic treatments. PMID:26770668

  18. Contribution of flow-volume curves to the detection of central airway obstruction*

    PubMed Central

    Raposo, Liliana Bárbara Perestrelo de Andrade e; Bugalho, António; Gomes, Maria João Marques

    2013-01-01

    OBJECTIVE: To assess the sensitivity and specificity of flow-volume curves in detecting central airway obstruction (CAO), and to determine whether their quantitative and qualitative criteria are associated with the location, type and degree of obstruction. METHODS: Over a four-month period, we consecutively evaluated patients with bronchoscopy indicated. Over a one-week period, all patients underwent clinical evaluation, flow-volume curve, bronchoscopy, and completed a dyspnea scale. Four reviewers, blinded to quantitative and clinical data, and bronchoscopy results, classified the morphology of the curves. A fifth reviewer determined the morphological criteria, as well as the quantitative criteria. RESULTS: We studied 82 patients, 36 (44%) of whom had CAO. The sensitivity and specificity of the flow-volume curves in detecting CAO were, respectively, 88.9% and 91.3% (quantitative criteria) and 30.6% and 93.5% (qualitative criteria). The most prevalent quantitative criteria in our sample were FEF50%/FIF50% ≥ 1, in 83% of patients, and FEV1/PEF ≥ 8 mL . L–1 . min–1, in 36%, both being associated with the type, location, and degree of obstruction (p < 0.05). There was concordance among the reviewers as to the presence of CAO. There is a relationship between the degree of obstruction and dyspnea. CONCLUSIONS: The quantitative criteria should always be calculated for flow-volume curves in order to detect CAO, because of the low sensitivity of the qualitative criteria. Both FEF50%/FIF50% ≥ 1 and FEV1/PEF ≥ 8 mL . L–1 . min–1 were associated with the location, type and degree of obstruction. PMID:24068266

  19. Obstructive airway in Morquio A syndrome, the past, the present and the future.

    PubMed

    Tomatsu, Shunji; Averill, Lauren W; Sawamoto, Kazuki; Mackenzie, William G; Bober, Michael B; Pizarro, Christian; Goff, Christopher J; Xie, Li; Orii, Tadao; Theroux, Mary

    2016-02-01

    Patients with severe tracheal obstruction in Morquio A syndrome are at risk of dying of sleep apnea and related complications. Tracheal obstruction also leads to life-threatening complications during anesthesia as a result of the difficulty in managing the upper airway due to factors inherent to the Morquio A syndrome, compounded by the difficulty in intubating the trachea. A detailed description of the obstructive pathology of the trachea is not available in the literature probably due to lack of a homogenous group of Morquio A patients to study at any one particular center. We present a series of cases with significant tracheal obstruction who were unrecognized due to the difficulty in interpreting tracheal narrowing airway symptoms. Our goal is to provide the guidelines in the management of these patients that allow earlier recognition and intervention of tracheal obstruction. Sagittal MRI images of the cervical spine of 28 Morquio A patients (12±8.14years) showed that19/28 (67.9%) patients had at least 25% tracheal narrowing and that narrowing worsened with age (all 8 patients over 15years had greater than 50% narrowing). Eight out of 28 patients were categorized as severe (>75%) tracheal narrowing when images were evaluated in neutral head and neck position. Of the 19 patients with tracheal narrowing, compression by the tortuous brachiocephalic artery was the most common cause (n=15). Evidence of such tracheal narrowing was evident as early as at 2years of age. The etiology of tracheal impingement by the brachiocephalic artery in Morquio A appears to be due to a combination of the narrow thoracic inlet crowding structures and the disproportionate growth of trachea and brachiocephalic artery in relationship to the chest cavity leading to tracheal tortuosity. In conclusion, tracheal narrowing, often due to impression from the crossing tortuous brachiocephalic artery, increases with age in Morquio A patients. Greater attention to the trachea is needed when

  20. Extracorporeal Lung Support as a Bridge to Airway Stenting and Radiotherapy for Airway-Obstructing Pancoast Tumor.

    PubMed

    McLenon, Melissa; Bittle, Gregory J; Jones, Kevin; Menaker, Jay; Pham, Si M; Iacono, Aldo T; Sachdeva, Ashutosh; Rajagopal, Keshava

    2016-07-01

    Venovenous (V-V) extracorporeal membrane oxygenation (ECMO) is used for respiratory failure that is suspected to be reversible (bridge to recovery), or as a bridge to lung transplantation. Patients with proximal airway obstruction due to endobronchial malignancy can develop acute respiratory failure, and may benefit from V-V ECMO as a bridge to airway intervention, further treatment, and eventual recovery. We describe a case of a superior sulcus tumor with tracheobronchial and superior vena cava invasion causing both respiratory failure and superior vena cava syndrome. This was treated successfully with V-V ECMO, bronchial stenting, and radiotherapy. PMID:27343540

  1. Mandibular distraction osteogenesis for the management of upper airway obstruction in children with micrognathia: a systematic review.

    PubMed

    Breik, O; Tivey, D; Umapathysivam, K; Anderson, P

    2016-06-01

    Mandibular distraction osteogenesis (MDO) is increasingly used for neonates and infants with upper airway obstruction secondary to micrognathia. This systematic review was conducted to determine the effectiveness of MDO in the treatment of airway obstruction. The databases searched included PubMed, Embase, Scopus, and grey literature sources. The inclusion criteria were applied to identify studies in children with clinical evidence of micrognathia/Pierre Robin sequence (PRS) who had failed conservative treatments, including both syndromic and non-syndromic patients. Overall 66 studies were included in this review. Primary MDO for the relief of upper airway obstruction was found to be successful at preventing tracheostomy in 95% of cases. Syndromic patients were found to have a four times greater odds of failure compared to those with isolated PRS. The most common causes of failure were previously undiagnosed lower airway obstruction, central apnoea, undiagnosed neurological abnormalities, and the presence of additional cardiovascular co-morbidities. MDO was less effective (81% success rate) at facilitating decannulation of tracheostomy-dependent children (P<0.0001). Failure in these patients was most commonly due to severe preoperative gastro-oesophageal reflux disease, swallowing dysfunction, and tracheostomy-related complications. The failure rate was higher when MDO was performed at an age of ≥24 months. More studies are needed to evaluate the long-term implications of MDO on facial development and long-term complications. PMID:26867668

  2. Small airway dysfunction and flow and volume bronchodilator responsiveness in patients with chronic obstructive pulmonary disease

    PubMed Central

    Pisi, Roberta; Aiello, Marina; Zanini, Andrea; Tzani, Panagiota; Paleari, Davide; Marangio, Emilio; Spanevello, Antonio; Nicolini, Gabriele; Chetta, Alfredo

    2015-01-01

    Background We investigated whether a relationship between small airways dysfunction and bronchodilator responsiveness exists in patients with chronic obstructive pulmonary disease (COPD). Methods We studied 100 (20 female; mean age: 68±10 years) patients with COPD (forced expiratory volume in 1 second [FEV1]: 55% pred ±21%; FEV1/forced vital capacity [FVC]: 53%±10%) by impulse oscillometry system. Resistance at 5 Hz and 20 Hz (R5 and R20, in kPa·s·L−1) and the fall in resistance from 5 Hz to 20 Hz (R5 – R20) were used as indices of total, proximal, and peripheral airway resistance; reactance at 5 Hz (X5, in kPa·s·L−1) was also measured. Significant response to bronchodilator (salbutamol 400 μg) was expressed as absolute (≥0.2 L) and percentage (≥12%) change relative to the prebronchodilator value of FEV1 (flow responders, FRs) and FVC (volume responders, VRs). Results Eighty out of 100 participants had R5 – R20 >0.03 kPa·s·L−1 (> upper normal limit) and, compared to patients with R5 – R20 ≤0.030 kPa·s·L−1, showed a poorer health status, lower values of FEV1, FVC, FEV1/FVC, and X5, along with higher values of residual volume/total lung capacity and R5 (P<0.05 for all comparisons). Compared to the 69 nonresponders and the 8 FRs, the 16 VRs had significantly higher R5 and R5 – R20 values (P<0.05), lower X5 values (P<0.05), and greater airflow obstruction and lung hyperinflation. Conclusion This study shows that peripheral airway resistance is increased in the vast majority of patients with COPD, who showed worse respiratory reactance, worse spirometry results, more severe lung hyperinflation, and poorer health status. Small airway dysfunction was also associated with the bronchodilator responsiveness in terms of FVC, but not in terms of FEV1. PMID:26150710

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

    PubMed

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

    2016-01-15

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

  4. Paradoxical responses to positive end-expiratory pressure in patients with airway obstruction during controlled ventilation*

    PubMed Central

    Caramez, Maria Paula; Borges, Joao B.; Tucci, Mauro R.; Okamoto, Valdelis N.; Carvalho, Carlos R. R.; Kacmarek, Robert M.; Malhotra, Atul; Velasco, Irineu Tadeu; Amato, Marcelo B. P.

    2008-01-01

    Objective To reevaluate the clinical impact of external positive end-expiratory pressure (external-PEEP) application in patients with severe airway obstruction during controlled mechanical ventilation. The controversial occurrence of a paradoxic lung deflation promoted by PEEP was scrutinized. Design External-PEEP was applied stepwise (2 cm H2O, 5-min steps) from zero-PEEP to 150% of intrinsic-PEEP in patients already submitted to ventilatory settings minimizing overinflation. Two commonly used frequencies during permissive hypercapnia (6 and 9/min), combined with two different tidal volumes (VT: 6 and 9 mL/kg), were tested. Setting A hospital intensive care unit. Patients Eight patients were enrolled after confirmation of an obstructive lung disease (inspiratory resistance, >20 cm H2O/L per sec) and the presence of intrinsic-PEEP (≥5 cm H2O) despite the use of very low minute ventilation. Interventions All patients were continuously monitored for intra-arterial blood gas values, cardiac output, lung mechanics, and lung volume with plethysmography. Measurements and Main Results Three different responses to external-PEEP were observed, which were independent of ventilatory settings. In the biphasic response, isovolume-expiratory flows and lung volumes remained constant during progressive PEEP steps until a threshold, beyond which overinflation ensued. In the classic overinflation response, any increment of external-PEEP caused a decrease in isovolume-expiratory flows, with evident overinflation. In the paradoxic response, a drop in functional residual capacity during external-PEEP application (when compared to zero-external-PEEP) was commonly accompanied by decreased plateau pressures and total-PEEP, with increased isovolume-expiratory flows. The paradoxic response was observed in five of the eight patients (three with asthma and two with chronic obstructive pulmonary disease) during at least one ventilator pattern. Conclusions External-PEEP application may

  5. Total body and exchangeable potassium in chronic airways obstruction: a controversial area?

    PubMed Central

    Boddy, K; Davies, D L; Howie, A D; Madkour, M M; Mahaffy, M E; Pack, A I

    1978-01-01

    Potassium deficiency is an important complication in the treatment of heart disease. However, there is a serious dichotomy in the literature. Severe potassium depletion has been reported in this condition when exchangeable potassium was measured whereas normal levels or marginal depletion were found in measurements of total body potassium. To clarify this situation, simultaneous measurements of total body potassium by whole-body counting, and of exchangeable potassium by isotope dilution using 43K, were made in 10 male subjects with established airways obstruction. Sequential determinations showed that exchangeable potassium increased up to 68 hours after administration, and values obtained at only 24 hours would have been a substantial underestimate. In this group of subjects neither total body nor exchangeable potassium at 48 hours was significantly different from the expected normal value. PMID:417419

  6. Occult central venous stenosis leading to airway obstruction after subtotal parathyroidectomy.

    PubMed

    Meiklejohn, Duncan A; Chan, Dylan K; Lalakea, M Lauren

    2016-07-01

    Subtotal parathyroidectomy may be indicated in patients with chronic renal failure and tertiary hyperparathyroidism, a population at increased risk for central venous stenosis (CVS) due to repeated vascular access. Here we report a case of complete upper airway obstruction precipitated by subtotal parathyroidectomy with ligation of anterior jugular vein collaterals in a patient with occult CVS. This case demonstrates a previously unreported risk of anterior neck surgery in patients with chronic renal failure. We present a review of the literature and discuss elements of the history and physical examination suggestive of occult CVS, with additional workup proposed for appropriate cases. Recommendations are discussed for perioperative and postoperative care in patients at increased risk for CVS. PMID:27434479

  7. Impact of Treatment with Continuous Positive Airway Pressure (CPAP) on Weight in Obstructive Sleep Apnea

    PubMed Central

    Quan, Stuart F.; Budhiraja, Rohit; Clarke, Denise P.; Goodwin, James L.; Gottlieb, Daniel J.; Nichols, Deborah A.; Simon, Richard D.; Smith, Terry W.; Walsh, James K.; Kushida, Clete A.

    2013-01-01

    Study Objective: To determine the impact of continuous positive airway pressure (CPAP) on weight change in persons with obstructive sleep apnea (OSA). Design, Setting, and Participants: The Apnea Positive Pressure Long-term Efficacy Study (APPLES) was a 6-month, randomized, double-blinded sham-controlled multicenter clinical trial conducted at 5 sites in the United States. Of 1,105 participants with an apnea hypopnea index ≥ 10 events/ hour initially randomized, 812 had body weight measured at baseline and after 6 months of study. Intervention: CPAP or Sham CPAP. Measurements: Body weight, height, hours of CPAP or Sham CPAP use, Epworth Sleepiness Scale score. Results: Participants randomized to CPAP gained 0.35 ± 5.01 kg, whereas those on Sham CPAP lost 0.70 ± 4.03 kg (mean ± SD, p = 0.001). Amount of weight gain with CPAP was related to hours of device adherence, with each hour per night of use predicting a 0.42 kg increase in weight. This association was not noted in the Sham CPAP group. CPAP participants who used their device ≥ 4 h per night on ≥ 70% of nights gained the most weight over 6 months in comparison to non-adherent CPAP participants (1.0 ± 5.3 vs. -0.3 ± 5.0 kg, p = 0.014). Conclusions: OSA patients using CPAP may gain a modest amount of weight with the greatest weight gain found in those most compliant with CPAP. Commentary: A commentary on this article appears in this issue on page 995. Citation: Quan SF; Budhiraja R; Clarke DP; Goodwin JL; Gottlieb DJ; Nichols DA; Simon RD; Smith TW; Walsh JK; Kushida CA. Impact of treatment with continuous positive airway pressure (CPAP) on weight in obstructive sleep apnea. J Clin Sleep Med 2013;9(10):989-993. PMID:24127141

  8. Air Trapping and Airflow Obstruction in Newborn Cystic Fibrosis Piglets

    PubMed Central

    Adam, Ryan J.; Michalski, Andrew S.; Bauer, Christian; Abou Alaiwa, Mahmoud H.; Gross, Thomas J.; Awadalla, Maged S.; Bouzek, Drake C.; Gansemer, Nicholas D.; Taft, Peter J.; Hoegger, Mark J.; Diwakar, Amit; Ochs, Matthias; Reinhardt, Joseph M.; Hoffman, Eric A.; Beichel, Reinhard R.; Meyerholz, David K.

    2013-01-01

    Rationale: Air trapping and airflow obstruction are being increasingly identified in infants with cystic fibrosis. These findings are commonly attributed to airway infection, inflammation, and mucus buildup. Objectives: To learn if air trapping and airflow obstruction are present before the onset of airway infection and inflammation in cystic fibrosis. Methods: On the day they are born, piglets with cystic fibrosis lack airway infection and inflammation. Therefore, we used newborn wild-type piglets and piglets with cystic fibrosis to assess air trapping, airway size, and lung volume with inspiratory and expiratory X-ray computed tomography scans. Micro–computed tomography scanning was used to assess more distal airway sizes. Airway resistance was determined with a mechanical ventilator. Mean linear intercept and alveolar surface area were determined using stereologic methods. Measurements and Main Results: On the day they were born, piglets with cystic fibrosis exhibited air trapping more frequently than wild-type piglets (75% vs. 12.5%, respectively). Moreover, newborn piglets with cystic fibrosis had increased airway resistance that was accompanied by luminal size reduction in the trachea, mainstem bronchi, and proximal airways. In contrast, mean linear intercept length, alveolar surface area, and lung volume were similar between both genotypes. Conclusions: The presence of air trapping, airflow obstruction, and airway size reduction in newborn piglets with cystic fibrosis before the onset of airway infection, inflammation, and mucus accumulation indicates that cystic fibrosis impacts airway development. Our findings suggest that early airflow obstruction and air trapping in infants with cystic fibrosis might, in part, be caused by congenital airway abnormalities. PMID:24168209

  9. [Automatic positive airway pressure in titration and treatment of the obstructive sleep apnea syndrome].

    PubMed

    Randerath, W J

    2007-04-01

    Although continuous airway pressure therapy (CPAP) represents the standard treatment for obstructive sleep apnea syndrome (OSAS) auto-adjusting CPAP (APAP) devices were developed which adapt the treatment pressure to the actual requirement of the patients. The aim of automatic CPAP therapy is to improve the patients' acceptance of positive pressure treatment. The devices react to respiratory flow, flattening of the inspiratory flow contour, snoring, generator speed or the upper airway impedance. In recent years several studies showed that auto CPAP effectively treats respiratory disturbances, improves sleep profile and the self-assessment of the patients equally as good as the gold standard constant CPAP. Moreover, APAP reduces the treatment pressure substantially. Although an improvement of the patient's compliance has not consistently been proven, most patients prefer APAP versus constant CPAP. APAP devices use different algorithms depending on the primary purpose of the application. Therefore, a clear distinction between automatic titration and treatment is of major relevance. While titration devices aim at the finding of one single pressure which is fixed to a constant CPAP device, automatic treatment means the chronic use of APAP at home for optimal adaptation of the treatment pressure to the actual requirements of the patient. A high constant CPAP level, huge pressure variability, insufficient compliance with constant CPAP may be indications for APAP treatment. The main reason for automatic titration is the standardisation of the initiation process. PMID:17455137

  10. Symbolic dynamics of pulse transit time and heart period in children with upper airway obstruction.

    PubMed

    Baumert, Mathias; Kohler, Mark; Pamula, Yvonne; Immanuel, Sarah A

    2015-08-01

    Upper airway obstruction (UAO) is a relatively common condition during childhood that is characterized by periods of partial or complete upper airway closure, resulting in restless sleep. It has also been suggested that UAO triggers early cardiovascular changes that may predispose to an increased risk of developing cardiovascular diseases later in life. The aim of this study was to assess the temporal dynamics of heart period (HP) and pulse transit time (PTT) during quite, event-free periods of sleep in children with UAO (n = 40) and matched healthy controls. The dynamics of HP and PTT were symbolized based on the sextiles of their distribution and words of length three were formed and classified into four types based on their patterns. Joint symbolic dynamics represent the concomitant occurrence of words in HP and PTT. Children with UAO showed a significantly increased frequency in word types of monotonously increasing and decreasing HP and PTT as well as joint dynamics across all stages of sleep. The dynamics of HP showed a marked sleep stage dependence, while PTT dynamics appeared to be relatively unaffected. In conclusion, cardiovascular dynamics are altered in children with UAO during scored event-free sleep, indicative of frequent bursts in sympathetic nervous system activity, possibly reflecting subcortical arousal responses to brief and subtle increases in UAO. PMID:26736629

  11. Effects of feeding sunflower oil or seal blubber oil to horses with recurrent airway obstruction

    PubMed Central

    Khol-Parisini, Annabella; van den Hoven, René; Leinker, Sandra; Hulan, Howard W.; Zentek, Juergen

    2007-01-01

    A crossover feeding trial was performed with 9 horses suffering from recurrent airway obstruction (RAO). The study aimed to determine whether ingestion of sunflower oil (SFO), rich in linoleic acid, or seal blubber oil (SBO), a source of long-chain omega-3 polyunsaturated fatty acids (LC n-3 PUFAs), changes the fatty acid (FA) ratios in plasma and leukocyte membrane phospholipids (PLs) or the leukocyte numbers or proportions of cell types in the airways. We also investigated diet-related changes in respiratory rate, maximum change in pleural pressure (ΔPplmax), dynamic compliance (Cdyn), and pulmonary resistance (RL). Each animal was fed hay and oats supplemented with 320 mg/kg body weight (BW) of either SFO or SBO for 10 wk. Before and after the feeding periods, we performed FA analyses, cytologic testing of the pulmonary epithelial lining fluid (PELF), clinical scoring, and pulmonary function testing. The results demonstrated that supplementary FAs were readily ingested and incorporated into leukocyte cell membranes. The n-6:n-3 FA ratios in plasma and leukocyte PLs were reduced after SBO supplementation, as were the PELF leukocyte counts (P < 0.05). On the other hand, pulmonary function and clinical signs were not markedly changed by the different dietary FAs. These results indicate a possible influence of dietary n-3 PUFAs on the pulmonary inflammation of horses with RAO. Further studies are warranted to address effects on inflammatory mediators and clinical outcome. PMID:17193883

  12. Obstructive Sleep Apnoea Modulates Airway Inflammation and Remodelling in Severe Asthma

    PubMed Central

    Taillé, Camille; Rouvel-Tallec, Anny; Stoica, Maria; Danel, Claire; Dehoux, Monique; Marin-Esteban, Viviana; Pretolani, Marina; Aubier, Michel; d’Ortho, Marie-Pia

    2016-01-01

    Background Obstructive sleep apnoea (OSA) is frequently observed in severe asthma but the causal link between the 2 diseases remains hypothetical. The role of OSA-related systemic and airway neutrophilic inflammation in asthma bronchial inflammation or remodelling has been rarely investigated. The aim of this study was to compare hallmarks of inflammation in induced sputum and features of airway remodelling in bronchial biopsies from adult patients with severe asthma with and without OSA. Materials and Methods An overnight polygraphy was performed in 55 patients referred for difficult-to-treat asthma, who complained of nocturnal respiratory symptoms, poor sleep quality or fatigue. We compared sputum analysis, reticular basement membrane (RBM) thickness, smooth muscle area, vascular density and inflammatory cell infiltration in bronchial biopsies. Results In total, 27/55 patients (49%) had OSA diagnosed by overnight polygraphy. Despite a moderate increase in apnoea-hypopnoea index (AHI; 14.2±1.6 event/h [5–35]), the proportion of sputum neutrophils was higher and that of macrophages lower in OSA than non-OSA patients, with higher levels of interleukin 8 and matrix metalloproteinase 9. The RBM was significantly thinner in OSA than non-OSA patients (5.8±0.4 vs. 7.8±0.4 μm, p<0.05). RBM thickness and OSA severity assessed by the AHI were negatively correlated (rho = -0.65, p<0.05). OSA and non-OSA patients did not differ in age, sex, BMI, lung function, asthma control findings or treatment. Conclusion Mild OSA in patients with severe asthma is associated with increased proportion of neutrophils in sputum and changes in airway remodelling. PMID:26934051

  13. Survival and Quality of Life Benefit after Endoscopic Management of Malignant Central Airway Obstruction

    PubMed Central

    Stratakos, Grigoris; Gerovasili, Vasiliki; Dimitropoulos, Charalampos; Giozos, Ioannis; Filippidis, Filippos T.; Gennimata, Sofia; Zarogoulidis, Paul; Zissimopoulos, Athanasios; Pataka, Athanasia; Koufos, Nikos; Zakynthinos, Spyros; Syrigos, Konstantinos; Koulouris, Nikos

    2016-01-01

    Background: Although interventional management of malignant central airway obstruction (mCAO) is well established, its impact on survival and quality of life (QoL) has not been extensively studied. Aim: We prospectively assessed survival, QoL and dyspnea (using validated EORTC questionnaire) in patients with mCAO 1 day before interventional bronchoscopy, 1 week after and every following month, in comparison to patients who declined this approach. Material/Patients/Methods: 36 patients underwent extensive interventional bronchoscopic management as indicated, whereas 12 declined. All patients received full chemotherapy and radiotherapy as indicated. Patients of the 2 groups were matched for age, comorbidities, type of malignancy and level of obstruction. Follow up time was 8.0±8.7 (range 1-38) months. Results: Mean survival for intervention and control group was 10±9 and 4±3 months respectively (p=0.04). QoL improved significantly in intervention group patients up to the 6th month (p<0.05) not deteriorating for those surviving up to 12 months. Dyspnea decreased in patients of the intervention group 1 month post procedure remaining reduced for survivors over the 12th month. Patients of the control group had worse QoL and dyspnea in all time points. Conclusions: Interventional management of patients with mCAO, may achieve prolonged survival with sustained significant improvement of QoL and dyspnea. PMID:27162537

  14. Dose response relation to oral theophylline in severe chronic obstructive airways disease.

    PubMed Central

    Chrystyn, H.; Mulley, B. A.; Peake, M. D.

    1988-01-01

    OBJECTIVE--To evaluate measurement of the trapped gas volume as a measure of respiratory function in patients with chronic obstructive airways disease and their response to treatment with theophylline. DESIGN--Patients able to produce consistent results on testing of respiratory function spent two weeks having dosage of theophylline adjusted to give individual pharmacokinetic data. This was followed by random assignment to four consecutive two month treatment periods--placebo and low, medium, and high dose, as assessed by serum concentrations of theophylline. Respiratory function and exercise performance was assessed at the end of each two month period. SETTING--Chest unit in district hospital. PATIENTS--Thirty eight patients with chronic bronchitis and moderate to severe chronic obstruction to airflow were recruited; 33 aged 53-73 years completed the study. INTERVENTIONS--Dosage of oral theophylline increased during two week optimisation period to 800 mg daily unless toxicity was predicted, when 400 mg was given. Targets for the steady state serum theophylline concentrations were 5-10 mg/l in the low dose period, 10-15 mg/l in the medium dose, and 15-20 mg/l in the high dose period. ENDPOINTS--Respiratory function as measured by forced expiratory volume in one second, forced vital capacity, peak expiratory flow rate, slow vital capacity, and static lung volumes using helium dilution and body plethysmography from which trapped gas volume was derived. Exercise performance assessed by six minute walking test and diary cards using visual analogue scale. MEASUREMENTS AND MAIN RESULTS--The forced expiratory volume in one second, forced vital capacity, and peak expiratory flow rate changed only slightly (about 13%) over the range of doses. There was a linear dose dependent fall of trapped gas volume from 1.84 l (SE 0.157) to 1.42 l (0.152), 1.05 l (0.128), and 0.67 l (0.102) during the placebo and low, medium, and high dose treatment periods. Mean walking distance

  15. The role of upper airway stimulation therapy in the multidisciplinary management approach of obstructive sleep apnea in the adult patient.

    PubMed

    Doghramji, Karl; Boon, Maurits

    2016-09-01

    Upper airway stimulation therapy (UAS) is a novel and effective treatment modality for obstructive sleep apnea (OSA). It is indicated for patients who are intolerant to traditional forms of therapy such as CPAP, and who have moderate to severe disease. Its success also relies upon the absence of certain upper airway structural and functional abnormalities. Therefore, the implementation of UAS necessitates a comprehensive evaluation with the coordinated efforts of otolaryngologist and sleep specialist, utilizing the consultative input of various other specialists. This same collaborative process also underlies the successful long-term followup care of patients following implantation surgery. Laryngoscope, 126:S9-S11, 2016. PMID:27572121

  16. Neonatal Pulmonary Macrophage Depletion Coupled to Defective Mucus Clearance Increases Susceptibility to Pneumonia and Alters Pulmonary Immune Responses.

    PubMed

    Saini, Yogesh; Wilkinson, Kristen J; Terrell, Kristy A; Burns, Kimberlie A; Livraghi-Butrico, Alessandra; Doerschuk, Claire M; O'Neal, Wanda K; Boucher, Richard C

    2016-02-01

    Resident immune cells (e.g., macrophages [MΦs]) and airway mucus clearance both contribute to a healthy lung environment. To investigate interactions between pulmonary MΦ function and defective mucus clearance, a genetic model of lysozyme M (LysM) promoter-mediated MΦ depletion was generated, characterized, and crossed with the sodium channel β subunit transgenic (Scnn1b-Tg) mouse model of defective mucus clearance. Diphtheria toxin A-mediated depletion of LysM(+) pulmonary MΦs in wild-type mice with normal mucus clearance resulted in lethal pneumonia in 24% of neonates. The pneumonias were dominated by Pasteurella pneumotropica and accompanied by emaciation, neutrophilic inflammation, and elevated Th1 cytokines. The incidence of emaciation and pneumonia reached 51% when LysM(+) MΦ depletion was superimposed on the airway mucus clearance defect of Scnn1b-Tg mice. In LysM(+) MΦ-depleted Scnn1b-Tg mice, pneumonias were associated with a broader spectrum of bacterial species and a significant reduction in airway mucus plugging. Bacterial burden (CFUs) was comparable between Scnn1b-Tg and nonpneumonic LysM(+) MΦ-depleted Scnn1b-Tg mice. However, the nonpneumonic LysM(+) MΦ-depleted Scnn1b-Tg mice exhibited increased airway inflammation, the presence of neutrophilic infiltration, and increased levels of inflammatory cytokines in bronchoalveolar lavage fluid compared with Scnn1b-Tg mice. Collectively, these data identify key MΦ-mucus clearance interactions with respect to both infectious and inflammatory components of muco-obstructive lung disease. PMID:26121027

  17. The dissection of reinforced endotracheal tube internal wall causing intraoperative airway obstruction under general anesthesia. Case report.

    PubMed

    Mercanoglu, Esra; Topuz, Derya; Kaya, Nur

    2013-01-01

    Endotracheal intubation is performed to establish a secure airway. However, this carries its risks and obstruction of an endotracheal tube (ETT) is a potentially life-threatening event. We report two cases with an obstruction of the resterilized, single use, spiral, reinforced endotracheal tubes by dissection of the internal wall. As a conclusion, we suggest not reusing and resterilizing single tubes in these cases to avoid a complication like dissection of the internal wall of the tube, as this has been the main cause. PMID:24565248

  18. The dissection of reinforced endotracheal tube internal wall causing intraoperative airway obstruction under general anesthesia: case report.

    PubMed

    Mercanoglu, Esra; Topuz, Derya; Kaya, Nur

    2013-01-01

    Endotracheal intubation is performed to establish a secure airway. However, this carries its risks and obstruction of an endotracheal tube (ETT) is a potentially life-threatening event. We report two cases with an obstruction of the resterilized, single use, spiral, reinforced endotracheal tubes by dissection of the internal wall. As a conclusion, we suggest not reusing and resterilizing single tubes in these cases to avoid a complication like dissection of the internal wall of the tube, as this has been the main cause. PMID:23931255

  19. Usefulness of intraoperative bronchoscopy during surgical repair of a congenital cardiac anomaly with possible airway obstruction: three cases report

    PubMed Central

    Oh, JongEun; Kim, Jung-won; Shin, Won-Jung; Park, Pyung Hwan

    2016-01-01

    Compression of the airway is relatively common in pediatric patients, although it is often an unrecognized complication of congenital cardiac and aortic arch anomalies. Aortopexy has been established as a surgical treatment for tracheobronchial obstruction associated with vascular anomaly, aortic arch anomaly, esophageal atresia, and tracheoesophageal fistula. The tissue-to-tissue arch repair technique could result in severe airway complication such as compression of the left main bronchus which was not a problem before the correction. We report three cases of corrective open heart surgery monitored by intraoperative bronchoscopy performed during prebypass, and performed immediately before weaning from bypass, to evaluate tracheobronchial obstruction caused by congenital, complex cardiac anomalies in the operating room. PMID:26885306

  20. Outgrowth of the Bacterial Airway Microbiome after Rhinovirus Exacerbation of Chronic Obstructive Pulmonary Disease

    PubMed Central

    Molyneaux, Philip L.; Mallia, Patrick; Cox, Michael J.; Footitt, Joseph; Willis-Owen, Saffron A. G.; Homola, Daniel; Trujillo-Torralbo, Maria-Belen; Elkin, Sarah; Kon, Onn Min; Cookson, William O. C.; Johnston, Sebastian L.

    2013-01-01

    Rationale: Rhinovirus infection is followed by significantly increased frequencies of positive, potentially pathogenic sputum cultures in chronic obstructive pulmonary disease (COPD). However, it remains unclear whether these represent de novo infections or an increased load of organisms from the complex microbial communities (microbiome) in the lower airways. Objectives: To investigate the effect of rhinovirus infection on the airway bacterial microbiome. Methods: Subjects with COPD (n = 14) and healthy control subjects with normal lung function (n = 17) were infected with rhinovirus. Induced sputum was collected at baseline before rhinovirus inoculation and again on Days 5, 15, and 42 after rhinovirus infection and DNA was extracted. The V3–V5 region of the bacterial 16S ribosomal RNA gene was amplified and pyrosequenced, resulting in 370,849 high-quality reads from 112 of the possible 124 time points. Measurements and Main Results: At 15 days after rhinovirus infection, there was a sixfold increase in 16S copy number (P = 0.007) and a 16% rise in numbers of proteobacterial sequences, most notably in potentially pathogenic Haemophilus influenzae (P = 2.7 × 10-20), from a preexisting community. These changes occurred only in the sputum microbiome of subjects with COPD and were still evident 42 days after infection. This was in contrast to the temporal stability demonstrated in the microbiome of healthy smokers and nonsmokers. Conclusions: After rhinovirus infection, there is a rise in bacterial burden and a significant outgrowth of Haemophilus influenzae from the existing microbiota of subjects with COPD. This is not observed in healthy individuals. Our findings suggest that rhinovirus infection in COPD alters the respiratory microbiome and may precipitate secondary bacterial infections. PMID:23992479

  1. High-Sensitivity C-Reactive Protein Can Reflect Small Airway Obstruction in Childhood Asthma

    PubMed Central

    Ko, A Ra; Sol, In Suk; Kim, Min Jung; Yoon, Seo Hee; Kim, Kyung Won; Kim, Kyu-Earn

    2016-01-01

    Purpose High-sensitivity assays enabled the identification of C-reactive protein (hs-CRP) at levels that were previously undetectable. We aimed to determine if hs-CRP could reflect airway inflammation in children, by comparing hs-CRP with spirometry and impulse oscillometry (IOS) parameters and symptomatic severities. Materials and Methods A total of 276 asthmatic children who visited Severance Children's Hospital from 2012–2014 were enrolled. Serum hs-CRP and pulmonary function tests were performed on the same day. Patients were divided into hs-CRP positive and negative groups (cut-off value, 3.0 mg/L). Results Of the 276 asthmatic children [median age 7.5 (5.9/10.1) years, 171 boys (62%)], 39 were hs-CRP positive and 237 were negative. Regarding spirometry parameters, we observed significant differences in maximum mid-expiratory flow, % predicted (FEF25–75) (p=0.010) between hs-CRP positive and negative groups, and a negative correlation between FEF25–75 and hs-CRP. There were significant differences in the reactance area (AX) (p=0.046), difference between resistance at 5 Hz and 20 Hz (R5–R20) (p=0.027), resistance at 5 Hz, % predicted (R5) (p=0.027), and reactance at 5 Hz, % predicted (X5) (p=0.041) between hs-CRP positive and negative groups. There were significant positive correlations between hs-CRP and R5 (r=0.163, p=0.008), and X5 (r=0.164, p=0.007). Spirometry and IOS parameters had more relevance in patients with higher blood neutrophil levels in comparison to hs-CRP. Conclusion Hs-CRP showed significant correlation with FEF25–75, R5, and X5. It can reflect small airway obstruction in childhood asthma, and it is more prominent in neutrophil dominant inflammation. PMID:26996570

  2. Impact of Facial Conformation on Canine Health: Brachycephalic Obstructive Airway Syndrome

    PubMed Central

    Packer, Rowena M. A.; Hendricks, Anke; Tivers, Michael S.; Burn, Charlotte C.

    2015-01-01

    The domestic dog may be the most morphologically diverse terrestrial mammalian species known to man; pedigree dogs are artificially selected for extreme aesthetics dictated by formal Breed Standards, and breed-related disorders linked to conformation are ubiquitous and diverse. Brachycephaly–foreshortening of the facial skeleton–is a discrete mutation that has been selected for in many popular dog breeds e.g. the Bulldog, Pug, and French Bulldog. A chronic, debilitating respiratory syndrome, whereby soft tissue blocks the airways, predominantly affects dogs with this conformation, and thus is labelled Brachycephalic Obstructive Airway Syndrome (BOAS). Despite the name of the syndrome, scientific evidence quantitatively linking brachycephaly with BOAS is lacking, but it could aid efforts to select for healthier conformations. Here we show, in (1) an exploratory study of 700 dogs of diverse breeds and conformations, and (2) a confirmatory study of 154 brachycephalic dogs, that BOAS risk increases sharply in a non-linear manner as relative muzzle length shortens. BOAS only occurred in dogs whose muzzles comprised less than half their cranial lengths. Thicker neck girths also increased BOAS risk in both populations: a risk factor for human sleep apnoea and not previously realised in dogs; and obesity was found to further increase BOAS risk. This study provides evidence that breeding for brachycephaly leads to an increased risk of BOAS in dogs, with risk increasing as the morphology becomes more exaggerated. As such, dog breeders and buyers should be aware of this risk when selecting dogs, and breeding organisations should actively discourage exaggeration of this high-risk conformation in breed standards and the show ring. PMID:26509577

  3. Impact of Facial Conformation on Canine Health: Brachycephalic Obstructive Airway Syndrome.

    PubMed

    Packer, Rowena M A; Hendricks, Anke; Tivers, Michael S; Burn, Charlotte C

    2015-01-01

    The domestic dog may be the most morphologically diverse terrestrial mammalian species known to man; pedigree dogs are artificially selected for extreme aesthetics dictated by formal Breed Standards, and breed-related disorders linked to conformation are ubiquitous and diverse. Brachycephaly--foreshortening of the facial skeleton--is a discrete mutation that has been selected for in many popular dog breeds e.g. the Bulldog, Pug, and French Bulldog. A chronic, debilitating respiratory syndrome, whereby soft tissue blocks the airways, predominantly affects dogs with this conformation, and thus is labelled Brachycephalic Obstructive Airway Syndrome (BOAS). Despite the name of the syndrome, scientific evidence quantitatively linking brachycephaly with BOAS is lacking, but it could aid efforts to select for healthier conformations. Here we show, in (1) an exploratory study of 700 dogs of diverse breeds and conformations, and (2) a confirmatory study of 154 brachycephalic dogs, that BOAS risk increases sharply in a non-linear manner as relative muzzle length shortens. BOAS only occurred in dogs whose muzzles comprised less than half their cranial lengths. Thicker neck girths also increased BOAS risk in both populations: a risk factor for human sleep apnoea and not previously realised in dogs; and obesity was found to further increase BOAS risk. This study provides evidence that breeding for brachycephaly leads to an increased risk of BOAS in dogs, with risk increasing as the morphology becomes more exaggerated. As such, dog breeders and buyers should be aware of this risk when selecting dogs, and breeding organisations should actively discourage exaggeration of this high-risk conformation in breed standards and the show ring. PMID:26509577

  4. Early onset airway obstruction in response to organic dust in the horse.

    PubMed

    Deaton, Christopher M; Deaton, Laura; Jose-Cunilleras, Eduard; Vincent, Thea L; Baird, Alan W; Dacre, K; Marlin, David J

    2007-03-01

    Equine recurrent airway obstruction (RAO) has been used as a naturally occurring model of human asthma. However, it is unknown whether there is an early-phase response in RAO. The aim of this study was to determine whether exposure to organic dust induces immediate changes in lung function in RAO-affected horses, which could be mediated by airway mast cells. Six RAO-affected horses in remission and six control horses were challenged with hay-straw dust suspension by nebulization. Total respiratory resistance at 1 Hz, measured by forced oscillation, was increased from 0.62 +/- 0.09 cmH(2)O.l(-1).s (mean +/- SE) to 1.23 +/- 0.20 cmH(2)O.l(-1).s 15 min after nebulization in control horses (P = 0.023) but did not change significantly in the RAO group. Total respiratory reactance at 1 Hz (P = 0.005) was significantly lower in the control horses (-0.77 +/- 0.07 cmH(2)O.l(-1).s) than in the RAO group (-0.49 +/- 0.04 cmH(2)O.l(-1).s) 15 min after nebulization. Bronchoalveolar lavage fluid (BALF) histamine concentration was significantly elevated 10 and 20 min postnebulization in control horses but not in RAO horses. Minimum reactance at 1 Hz in the early postnebulization period significantly correlated with both prechallenge BALF mast cell numbers (r = -0.65, P = 0.02) and peak BALF histamine concentration postnebulization (r = -0.61, P = 0.04). In conclusion, RAO horses, unlike human asthmatic patients, do not exhibit an early-phase response. However, healthy control horses do demonstrate a mild but significant early (<20 min) phase response to inhaled organic dust. This response may serve to decrease the subsequent dose of dust inhaled and as such provide a protective mechanism, which may be compromised in RAO horses. PMID:17158251

  5. Continuous Positive Airway Pressure Compliance in Patients with Obstructive Sleep Apnea

    PubMed Central

    Afsharpaiman, Shahla; Vahedi, Encieh; Aqaee, Hossein

    2016-01-01

    Background: Obstructive sleep apnea (OSA) is a common condition in adults. In most cases, first-line therapy includes treatment with positive airway pressure devices. However, because of discomfort, continuous positive airway pressure (CPAP) compliance is often poor. To determine the willingness of patients to use CPAP device, the relationship of demographic and polysomnographic variables with tolerance and the willingness to use CPAP, was evaluated. Materials and Methods: In this cross-sectional study, 120 OSA patients who were treated with CPAP in Baqiyatallah Hospital, Tehran, Iran, were selected by convenience sampling. Polysomnographic variables, willingness to use CPAP for short and long periods of time and possible complications were evaluated. Results: One hundred-twenty cases with a mean age of 53±10.3 years were assessed. The mean Epworth Sleepiness Scale (ESS) score was 11.9 ± 6.2 in CPAP users versus 11.8±6.1 in patients who did not use CPAP. The willingness to use CPAP for short-term was significantly different between the two groups (P=0.008). The average minimum oxygen saturation rate of patients was 75.21% in CPAP users versus 71.63% in non CPAP users. Also, the average desaturation index was higher in CPAP users (54.5 vs. 44.98). The mean ESS was 14.03 ± 6.19 in those who accepted long-term treatment versus 8.85 ± 4.89 (P=0.003). Skin wounds and rhinitis were reported in 4.1% and 4.1% of patients, respectively. Conclusion: It is concluded that high CPAP compliance rates are achievable through comprehensive CPAP therapy.

  6. Upper Airway Stimulation for Obstructive Sleep Apnea: Self-Reported Outcomes at 24 Months

    PubMed Central

    Soose, Ryan J.; Woodson, B. Tucker; Gillespie, M. Boyd; Maurer, Joachim T.; de Vries, Nico; Steward, David L.; Strohl, Kingman P.; Baskin, Jonathan Z.; Padhya, Tapan A.; Badr, M. Safwan; Lin, Ho-sheng; Vanderveken, Olivier M.; Mickelson, Sam; Chasens, Eileen; Strollo, Patrick J.

    2016-01-01

    Objectives: To evaluate the long-term (24-mo) effect of cranial nerve upper airway stimulation (UAS) therapy on patient-centered obstructive sleep apnea (OSA) outcome measures. Methods: Prospective, multicenter, cohort study of 126 patients with moderate to severe OSA who had difficulty adhering to positive pressure therapy and received the surgically implanted UAS system. Outcomes were measured at baseline and postoperatively at 12 mo and 24 mo, and included self- and bedpartner-report of snoring intensity, Epworth Sleepiness Scale (ESS), and Functional Outcomes of Sleep Questionnaire (FOSQ). Additional analysis included FOSQ subscales, FOSQ-10, and treatment effect size. Results: Significant improvement in mean FOSQ score was observed from baseline (14.3) to 12 mo (17.3), and the effect was maintained at 24 mo (17.2). Similar improvements and maintenance of effect were seen with all FOSQ subscales and FOSQ-10. Subjective daytime sleepiness, as measured by mean ESS, improved significantly from baseline (11.6) to 12 mo (7.0) and 24 mo (7.1). Self-reported snoring severity showed increased percentage of “no” or “soft” snoring from 22% at baseline to 88% at 12 mo and 91% at 24 mo. UAS demonstrated large effect size (> 0.8) at 12 and 24 mo for overall ESS and FOSQ measures, and the effect size compared favorably to previously published effect size with other sleep apnea treatments. Conclusions: In a selected group of patients with moderate to severe OSA and body mass index ≤ 32 kg/m2, hypoglossal cranial nerve stimulation therapy can provide significant improvement in important sleep related quality-of-life outcome measures and the effect is maintained across a 2-y follow-up period. Citation: Soose RJ, Woodson BT, Gillespie MB, Maurer JT, de Vries N, Steward DL, Strohl KP, Baskin JZ, Padhya TA, Badr MS, Lin H, Vanderveken OM, Mickelson S, Chasens E, Strollo Jr PJ, STAR Trial Investigators. Upper airway stimulation for obstructive sleep apnea: self

  7. Abdominal adiposity and obstructive airway disease: testing insulin resistance and sleep disordered breathing mechanisms

    PubMed Central

    2012-01-01

    Background This study examined associations of abdominal adiposity with lung function, asthma symptoms and current doctor-diagnosed asthma and mediation by insulin resistance (IR) and sleep disordered breathing (SDB). Methods A random sample of 2500 households was drawn from the community of Whyalla, South Australia (The Whyalla Intergenerational Study of Health, WISH February 2008 - July 2009). Seven-hundred twenty-two randomly selected adults (≥18 years) completed clinical protocols (32.2% response rate). Lung function was measured by spirometry. Post-bronchodilator FEV1/FVC was used to measure airway obstruction and reversibility of FEV1 was calculated. Current asthma was defined by self-reported doctor-diagnosis and evidence of currently active asthma. Symptom scores for asthma (CASS) and SDB were calculated. Intra-abdominal fat (IAF) was estimated using dual-energy x-ray absorptiometry (DXA). IR was calculated from fasting glucose and insulin concentrations. Results The prevalence of current doctor-diagnosed asthma was 19.9% (95% CI 16.7 – 23.5%). The ratio of observed to expected cases given the age and sex distribution of the population was 2.4 (95%CI 2.1, 2.9). IAF was not associated with current doctor-diagnosed asthma, FEV1/FVC or FEV1 reversibility in men or women but was positively associated with CASS independent of IR and SDB in women. A 1% increase in IAF was associated with decreases of 12 mL and 20 mL in FEV1 and FVC respectively in men, and 4 mL and 7 mL respectively in women. SDB mediated 12% and 26% of these associations respectively in men but had minimal effects in women. Conclusions In this population with an excess of doctor-diagnosed asthma, IAF was not a major factor in airway obstruction or doctor-diagnosed asthma, although women with higher IAF perceived more severe asthma symptoms which did not correlate with lower FEV1. Higher IAF was significantly associated with lower FEV1 and FVC and in men SDB mechanisms may

  8. Analysis of genomic copy number variation in equine recurrent airway obstruction (heaves).

    PubMed

    Ghosh, S; Das, P J; McQueen, C M; Gerber, V; Swiderski, C E; Lavoie, J-P; Chowdhary, B P; Raudsepp, T

    2016-06-01

    We explored the involvement of genomic copy number variants (CNVs) in susceptibility to recurrent airway obstruction (RAO), or heaves-an asthmalike inflammatory disease in horses. Analysis of 16 RAO-susceptible (cases) and six RAO-resistant (control) horses on a custom-made whole-genome 400K equine tiling array identified 245 CNV regions (CNVRs), 197 previously known and 48 new, distributed on all horse autosomes and the X chromosome. Among the new CNVRs, 30 were exclusively found in RAO cases and were further analyzed by quantitative PCR, including additional cases and controls. Suggestive association (P = 0.03; corrected P = 0.06) was found between RAO and a loss on chromosome 5 involving NME7, a gene necessary for ciliary functions in lungs and involved in primary ciliary dyskinesia in humans. The CNVR could be a potential marker for RAO susceptibility but needs further study in additional RAO cohorts. Other CNVRs were not associated with RAO, although several involved genes of interest, such as SPI2/SERPINA1 from the serpin gene family, which are associated with chronic obstructive pulmonary disease and asthma in humans. The SPI2/SERPINA1 CNVR showed striking variation among horses, but it was not significantly different between RAO cases and controls. The findings provide baseline information on the relationship between CNVs and RAO susceptibility. Discovery of new CNVs and the use of a larger population of RAO-affected and control horses are needed to shed more light on their significance in modulating this complex and heterogeneous disease. PMID:26932307

  9. Respirable quartz dust exposure and airway obstruction: a systematic review and meta-analysis.

    PubMed

    Brüske, Irene; Thiering, Elisabeth; Heinrich, Joachim; Huster, Katharina M; Nowak, Dennis

    2014-08-01

    Studies on exposure to respirable quartz dust at the workplace and the development of chronic obstructive pulmonary disease (COPD) were selected into a systematic review and meta-analysed to obtain an overall estimate of forced expiratory volume in 1 s (FEV1) and FEV1/forced vital capacity (FVC) reduction. PubMed and Embase were searched from 1970 to 2010. In total, 257 cross-sectional and longitudinal studies were identified that reported on inorganic dust exposure and had available lung function data. Of the 55 publications which met our inclusion criteria, 11 reported on associations with occupational exposure to respirable quartz dust. The combined average effect estimate of respirable quartz dust on spirometric parameters was obtained using a random effects model meta-analysis. Between-study heterogeneity was assessed via the I(2) statistic. Most studies found a significant negative association of FEV1 and FEV1/FVC related to increasing exposure to crystalline quartz at the workplace. One study found an effect only for smokers, and one did not observe such an effect at all. The meta-analysis of cross-sectional studies showed that the mean ratio FEV1 to FVC was reduced and FEV1 of workers exposed to respirable quartz dust was 4.6% less than predicted compared with workers with no/low exposure. Both results showed a statistically significant difference. Occupational exposure to respirable quartz dust was associated with a statistically significant decrease in FEV1 and FEV1/FVC, revealing airway obstruction consistent with COPD. PMID:24863263

  10. Clinical, functional and pathological correspondence in early stage idiopathic pulmonary fibrosis: evidence for small airway obstruction 1-2.

    PubMed

    Myre, M; Allard, S; Bernard, C; Martin, R R

    1988-01-01

    We describe the clinical, physiological and pathological features of 23 subjects with early stage idiopathic pulmonary fibrosis. Thirteen subjects who had no symptoms had been fortuitously recruited by a routine chest radiograph, whereas the 10 other subjects complained of dyspnea. Twenty-one subjects showed only light to moderate extent of abnormalities on the chest radiograph. Fourteen subjects had a reduced vital capacity whereas 16 and 17 showed a reduced pulmonary compliance and an increase in lung elastic recoil, respectively. Transfer factor was significantly reduced in 18 subjects. Evidence for significant airway obstruction, mainly located at the peripheral level, was demonstrated by a reduced specific lung conductance and upstream conductance in 13 subjects. Airway obstruction was not associated with smoking habits. Bronchial hyperresponsiveness was noted in 50% of the 18 subjects studied. Although fibrosis was mild to moderate in 15 instances, it was only focal, i.e. at least one zone of normal parenchyma in the lung specimen in 17 subjects. Peribronchial fibrosis was established in 8/11 satisfactory biopsy specimens. Significant correlations were observed between rales, the radiological score, some functional indices and the characteristics of fibrosis. We conclude that small airway obstruction documented by physiological and pathological means is frequent in early stage idiopathic pulmonary fibrosis. PMID:3420306

  11. Hyper-osmolarity and calcium chelation: Effects on cystic fibrosis mucus.

    PubMed

    Ermund, Anna; Meiss, Lauren N; Gustafsson, Jenny K; Hansson, Gunnar C

    2015-10-01

    A non-functional Cystic Fibrosis Transmembrane conductance Regulator (CFTR) leads to the disease cystic fibrosis (CF). Although the CFTR is expressed in multiple organs, pulmonary disease is the major cause of illness and death in patients with CF. Stagnant mucus, causing airway obstruction, bacterial overgrowth, persistent inflammation and tissue destruction characterizes the disease, but how the defect in CFTR function is coupled to the mucus phenotype is still controversial. We have recently shown that bicarbonate ions passing through CFTR are necessary for proper unfolding of the MUC2 mucin, thus highlighting the importance of bicarbonate ion transport via the CFTR and the ability of these ions to raise the pH and chelate calcium bound to the mucin as the important steps in forming normal mucus. In order to find potential CF treatments and expand our knowledge about the usefulness of bicarbonate as an active ingredient in formulations to alleviate mucus plugging, we used an Ussing-type chamber and explants from the F508del-CFTR mutant mouse ileum to test the effect of calcium chelators on mucus attachment, either in isolation or in combination with osmolytes such as mannitol or hypertonic saline. We found that increasing the concentration of bicarbonate, both alone or in combination with increased osmolarity of the solution, detached the otherwise attached CF mucus. PMID:26134505

  12. Upper Airway Stimulation for Obstructive Sleep Apnea: Durability of the Treatment Effect at 18 Months

    PubMed Central

    Strollo, Patrick J.; Gillespie, M. Boyd; Soose, Ryan J.; Maurer, Joachim T.; de Vries, Nico; Cornelius, Jason; Hanson, Ronald D.; Padhya, Tapan A.; Steward, David L.; Woodson, B. Tucker; Verbraecken, Johan; Vanderveken, Olivier M.; Goetting, Mark G.; Feldman, Neil; Chabolle, Frédéric; Badr, M. Safwan; Randerath, Winfried; Strohl, Kingman P.

    2015-01-01

    , Strohl KP, Stimulation Therapy for Apnea Reduction Trial Group. Upper airway stimulation for obstructive sleep apnea: durability of the treatment effect at 18 months. SLEEP 2015;38(10):1593–1598. PMID:26158895

  13. Effects of second hand smoke on airway secretion and mucociliary clearance

    PubMed Central

    Liu, Yanyan; Di, Y. Peter

    2012-01-01

    The airway acts as the first defense against inhaled pathogens and particulate matter from the environment. One major way for the airway to clear inhaled foreign objects is through mucociliary clearance (MCC), an important component of the respiratory innate immune defense against lung disease. MCC is characterized by the upward movement of mucus by ciliary motion that requires a balance between the volume and composition of the mucus, adequate periciliary liquid (PCL) volume, and normal ciliary beat frequency (CBF). Airway surface fluid (ASL) is a thin layer liquid that consists of the highly viscous mucus upper “gel” layer, and the watery lubricating lower “sol” layer. Mucus production, secretion and clearance are considered to play a critical role in maintenance of airway health because it maintains hydration in the airway and traps particulates, bacteria, and viruses. Different types of epithelial cells, including secretory cells, and ciliated cells, contribute to the MCC function. Cigarette smoke (CS) contains chemicals and particulates that significantly affect airway secretion. Active and passive CS-induced chronic obstructive pulmonary disease (COPD) is frequently associated with hyperplasia of goblet cells and submucosal glands (SMGs), thus increasing the secretory capacity of the airways that impairs MCC. PMID:22973232

  14. Early events in the pathogenesis of chronic obstructive pulmonary disease. Smoking-induced reprogramming of airway epithelial basal progenitor cells.

    PubMed

    Shaykhiev, Renat; Crystal, Ronald G

    2014-12-01

    The airway epithelium is the primary site of the earliest pathologic changes induced by smoking, contributing to the development of chronic obstructive pulmonary disease (COPD). The normal human airway epithelium is composed of several major cell types, including differentiated ciliated and secretory cells, intermediate undifferentiated cells, and basal cells (BC). BC contain the stem/progenitor cell population responsible for maintenance of the normally differentiated airway epithelium. Although inflammatory and immune processes play a significant role in the pathogenesis of COPD, the earliest lesions include hyperplasia of the BC population, suggesting that the disease may start with this cell type. Apart from BC hyperplasia, smoking induces a number of COPD-relevant airway epithelial remodeling phenotypes that are likely initiated in the BC population, including mucous cell hyperplasia, squamous cell metaplasia, epithelial-mesenchymal transition, altered ciliated and nonmucous secretory cell differentiation, and suppression of junctional barrier integrity. Significant progress has been recently made in understanding the biology of human airway BC, including gene expression features, stem/progenitor, and other functions, including interaction with other airway cell types. Accumulating evidence suggests that human airway BC function as both sensors and cellular sources of various cytokines and growth factors relevant to smoking-associated airway injury, as well as the origin of various molecular and histological phenotypes relevant to the pathogenesis of COPD. In the context of these considerations, we suggest that early BC-specific smoking-induced molecular changes are critical to the pathogenesis of COPD, and these represent a candidate target for novel therapeutic approaches to prevent COPD progression in susceptible individuals. PMID:25525728

  15. Evidence of prednisolone induced mood change ('steroid euphoria') in patients with chronic obstructive airways disease.

    PubMed Central

    Swinburn, C R; Wakefield, J M; Newman, S P; Jones, P W

    1988-01-01

    1. It is a clinical impression that some patients given oral corticosteroids develop a sense of wellbeing that is 'inappropriate' to improvements in physical health. This has been termed steroid 'euphoria', but unlike steroid-induced psychosis it has not been documented. 2. To test for the size and frequency of this phenomenon, 20 patients with severe chronic obstructive airways disease (mean FEV1 0.86 l) were given 30 mg of prednisolone for 14 days, after a period of placebo administration in a single-blind study. 3. Lung spirometry and arterial saturation during exercise were measured serially, together with established measures of mood state. 4. No changes in spirometry or arterial saturation during exercise were detected until 7 days of active therapy. 5. Mood state did not change during the placebo period, but small significant reductions in anxiety and depression were measured after 3 days of prednisolone and before any measurable improvement in lung function. Mood state did not then further improve, despite measurable improvements in lung spirometry. 6. This is evidence that prednisolone may produce a mild 'inappropriate' sense of wellbeing within a population receiving the drug, rather than as an occasional idiosyncratic response. PMID:3242575

  16. Adherence to Continuous Positive Airway Pressure Treatment for Obstructive Sleep Apnea: Implications for Future Interventions

    PubMed Central

    Weaver, Terri E.; Sawyer, Amy M.

    2010-01-01

    Adherence to continuous positive airway pressure (CPAP) treatment for obstructive sleep apnea (OSA) is a critical problem with adherence rates ranging from 30–60%. Poor adherence to CPAP is widely recognized as a significant limiting factor in treating OSA, reducing the overall effectiveness of the treatment and leaving many OSA patients at heightened risk for comorbid conditions, impaired function and quality of life. The extant literature examining adherence to CPAP provides critical insight to measuring adherence outcomes, defining optimal adherence levels, and predicting CPAP adherence. This research has revealed salient factors that are associated with or predict CPAP adherence and may guide the development of interventions to promote CPAP adherence. Over the past 10 years, intervention studies to promote CPAP adherence have incorporated a multitude of strategies including education, support, cognitive behavioral approaches, and mixed strategies. This review of the current state of science of CPAP adherence will (1) synthesize the extant literature with regard to measuring, defining, and predicting CPAP adherence, (2) review published intervention studies aimed at promoting CPAP adherence, and (3) suggest directions for future empiric study of adherence to CPAP that will have implications for translational science. Our current understanding of CPAP adherence suggests that adherence is a multi-factorial, complex clinical problem that requires similarly designed approaches to effectively address poor CPAP adherence in the OSA population. PMID:20308750

  17. A systematic review of continuous positive airway pressure for obstructive sleep apnoea-hypopnoea syndrome.

    PubMed

    McDaid, Catriona; Durée, Kate H; Griffin, Susan C; Weatherly, Helen L A; Stradling, John R; Davies, Robert J O; Sculpher, Mark J; Westwood, Marie E

    2009-12-01

    We conducted a systematic review of current evidence on the effectiveness of continuous positive airway pressure (CPAP) for treatment of obstructive sleep apnoea-hypopnoea syndrome (OSAHS). The primary outcomes were subjective sleepiness, using Epworth Sleepiness Scale (ESS) and objective sleepiness using Maintenance of Wakefulness Test (MWT) and Multiple Sleep Latency Test (MSLT). Mean difference (MD) in endpoints was used to compare CPAP to usual care, placebo and dental devices. The analysis was stratified by symptom and disease severity at baseline. CPAP significantly reduced ESS score compared to control (MD -2.7, 95% CI -3.45, -1.96). The benefit was greatest in patients whose symptoms were severe at baseline: severely symptomatic population (MD -5.0, -6.5, -3.5); moderate (MD -2.3, -3.0, -1.6); mild (MD -1.1, -1.8, -0.3). CPAP significantly improved MWT score compared to control (MD 3.3, 1.3, 5.3) but not on the MSLT. There was no statistically significant difference between CPAP and dental devices on the ESS, MWT or MSLT, in a population with moderate symptoms. There was some evidence of benefit for blood pressure with CPAP compared to control. CPAP is an effective treatment for OSAHS in moderate to severe symptomatic patients and there may be benefits for mild symptoms. Dental devices may be a treatment option for moderate symptoms. PMID:19362029

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

    PubMed Central

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

    2015-01-01

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

  19. Cigarette smoke exposure induces CFTR internalization and insolubility, leading to airway surface liquid dehydration.

    PubMed

    Clunes, Lucy A; Davies, Catrin M; Coakley, Raymond D; Aleksandrov, Andrei A; Henderson, Ashley G; Zeman, Kirby L; Worthington, Erin N; Gentzsch, Martina; Kreda, Silvia M; Cholon, Deborah; Bennett, William D; Riordan, John R; Boucher, Richard C; Tarran, Robert

    2012-02-01

    Cigarette smoke (CS) exposure induces mucus obstruction and the development of chronic bronchitis (CB). While many of these responses are determined genetically, little is known about the effects CS can exert on pulmonary epithelia at the protein level. We, therefore, tested the hypothesis that CS exerts direct effects on the CFTR protein, which could impair airway hydration, leading to the mucus stasis characteristic of both cystic fibrosis and CB. In vivo and in vitro studies demonstrated that CS rapidly decreased CFTR activity, leading to airway surface liquid (ASL) volume depletion (i.e., dehydration). Further studies revealed that CS induced internalization of CFTR. Surprisingly, CS-internalized CFTR did not colocalize with lysosomal proteins. Instead, the bulk of CFTR shifted to a detergent-resistant fraction within the cell and colocalized with the intermediate filament vimentin, suggesting that CS induced CFTR movement into an aggresome-like, perinuclear compartment. To test whether airway dehydration could be reversed, we used hypertonic saline (HS) as an osmolyte to rehydrate ASL. HS restored ASL height in CS-exposed, dehydrated airway cultures. Similarly, inhaled HS restored mucus transport and increased clearance in patients with CB. Thus, we propose that CS exposure rapidly impairs CFTR function by internalizing CFTR, leading to ASL dehydration, which promotes mucus stasis and a failure of mucus clearance, leaving smokers at risk for developing CB. Furthermore, our data suggest that strategies to rehydrate airway surfaces may provide a novel form of therapy for patients with CB. PMID:21990373

  20. Surgical Modifications of the Upper Airway for Obstructive Sleep Apnea in Adults: A Systematic Review and Meta-Analysis

    PubMed Central

    Caples, Sean M.; Rowley, James A.; Prinsell, Jeffrey R.; Pallanch, John F.; Elamin, Mohamed B.; Katz, Sheri G.; Harwick, John D.

    2010-01-01

    A substantial portion of patients with obstructive sleep apnea (OSA) seek alternatives to positive airway pressure (PAP), the usual first-line treatment for the disorder. One option is upper airway surgery. As an adjunct to the American Academy of Sleep Medicine (AASM) Standards of Practice paper, we conducted a systematic review and meta-analysis of literature reporting outcomes following various upper airway surgeries for the treatment of OSA in adults, including maxillomandibular advancement (MMA), pharyngeal surgeries such as uvulopharyngopalatoplasty (UPPP), laser assisted uvulopalatoplasty (LAUP), and radiofrequency ablation (RFA), as well as multi-level and multi-phased procedures. We found that the published literature is comprised primarily of case series, with few controlled trials and varying approaches to pre-operative evaluation and post-operative follow-up. We include surgical morbidity and adverse events where reported but these were not systematically analyzed. Utilizing the ratio of means method, we used the change in the apnea-hypopnea index (AHI) as the primary measure of efficacy. Substantial and consistent reductions in the AHI were observed following MMA; adverse events were uncommonly reported. Outcomes following pharyngeal surgeries were less consistent; adverse events were reported more commonly. Papers describing positive outcomes associated with newer pharyngeal techniques and multi-level procedures performed in small samples of patients appear promising. Further research is needed to better clarify patient selection, as well as efficacy and safety of upper airway surgery in those with OSA. Citation: Caples SM; Rowley JA; Prinsell JR; Pallanch JF; Elamin MB; Katz SG; Harwick JD. Surgical modifications of the upper airway for obstructive sleep apnea in adults: a systematic review and meta-analysis. SLEEP 2010;33(10):1396-1407. PMID:21061863

  1. DNA Methylation Is Globally Disrupted and Associated with Expression Changes in Chronic Obstructive Pulmonary Disease Small Airways

    PubMed Central

    Chari, Raj; Thu, Kelsie L.; Wilson, Ian M.; Cotton, Allison M.; Kennett, Jennifer Y.; Zhang, May; Lonergan, Kim M.; Steiling, Katrina; Brown, Carolyn J.; McWilliams, Annette; Ohtani, Keishi; Lenburg, Marc E.; Sin, Don D.; Spira, Avrum; MacAulay, Calum E.; Lam, Stephen; Lam, Wan L.

    2014-01-01

    DNA methylation is an epigenetic modification that is highly disrupted in response to cigarette smoke and involved in a wide spectrum of malignant and nonmalignant diseases, but surprisingly not previously assessed in small airways of patients with chronic obstructive pulmonary disease (COPD). Small airways are the primary sites of airflow obstruction in COPD. We sought to determine whether DNA methylation patterns are disrupted in small airway epithelia of patients with COPD, and evaluate whether changes in gene expression are associated with these disruptions. Genome-wide methylation and gene expression analysis were performed on small airway epithelial DNA and RNA obtained from the same patient during bronchoscopy, using Illumina’s Infinium HM27 and Affymetrix’s Genechip Human Gene 1.0 ST arrays. To control for known effects of cigarette smoking on DNA methylation, methylation and gene expression profiles were compared between former smokers with and without COPD matched for age, pack-years, and years of smoking cessation. Our results indicate that aberrant DNA methylation is (1) a genome-wide phenomenon in small airways of patients with COPD, and (2) associated with altered expression of genes and pathways important to COPD, such as the NF-E2–related factor 2 oxidative response pathway. DNA methylation is likely an important mechanism contributing to modulation of genes important to COPD pathology. Because these methylation events may underlie disease-specific gene expression changes, their characterization is a critical first step toward the development of epigenetic markers and an opportunity for developing novel epigenetic therapeutic interventions for COPD. PMID:24298892

  2. Characterisation of Brachycephalic Obstructive Airway Syndrome in French Bulldogs Using Whole-Body Barometric Plethysmography

    PubMed Central

    Liu, Nai-Chieh; Sargan, David R.; Adams, Vicki J.; Ladlow, Jane F.

    2015-01-01

    Brachycephalic obstructive airway syndrome (BOAS) is an important health and welfare problem in several popular dog breeds. Whole-body barometric plethysmography (WBBP) is a non-invasive method that allows safe and repeated quantitative measurements of respiratory cycles on unsedated dogs. Here respiratory flow traces in French bulldogs from the pet population were characterised using WBBP, and a computational application was developed to recognise affected animals. Eighty-nine French bulldogs and twenty non-brachycephalic controls underwent WBBP testing. A respiratory functional grading system was used on each dog based on respiratory signs (i.e. respiratory noise, effort, etc.) before and after exercise. For development of an objective BOAS classifier, functional Grades 0 and I were considered to have insignificant clinical signs (termed here BOAS-) and Grades II and III to have significant signs (termed here BOAS+). A comparison between owner-perception of BOAS and functional grading revealed that 60 % of owners failed to recognise BOAS in dogs that graded BOAS+ in this study.WBBP flow traces were found to be significantly different between non-brachycephalic controls and Grade 0 French bulldogs; BOAS- and BOAS+ French bulldogs. A classifier was developed using quadratic discriminant analysis of the respiratory parameters to distinguish BOAS- and BOAS + French bulldogs, and a BOAS Index was calculated for each dog. A cut-off value of the BOAS Index was selected based on a receiver operating characteristic (ROC) curve. Sensitivity, specificity, positive predictive value, and negative predictive value of the classifier on the training group (n=69) were 0.97, 0.93, 0.95, and 0.97, respectively. The classifier was validated using a test group of French bulldogs (n=20) with an accuracy of 0.95. WBBP offers objective screening for the diagnosis of BOAS in French Bulldogs. The technique may be applied to other brachycephalic breeds affected by BOAS, and possibly to

  3. Reaginic antibodies from horses with recurrent airway obstruction produce mast cell stimulation.

    PubMed

    Moran, G; Folch, H; Henriquez, C; Ortloff, A; Barria, M

    2012-12-01

    Reaginic antibodies (IgE and some IgG subclasses) and mast cells play important roles in the induction of type I immediate hypersensitivity reactions. These antibodies bind through their Fc fragment to high affinity receptors (FcεRI) present in the membrane of mast cells and basophils. The cross-linking of the receptor initiates a coordinated sequence of biochemical and morphological events that results in exocytosis of secretory granules containing pre-formed inflammatory mediators, secretion of newly formed lipid mediators, and secretion of cytokines. Previously, several studies have investigated the role of reaginic antibodies in the pathogenesis of Recurrent Airway Obstruction (RAO). However, whereas the immunological aspects of RAO have been extensively studied, the precise sequence of events involved in the pathogenesis remains not completely understood, and the role of IgE in this disease remains controversial. Therefore, in this study, several bioassays were conducted to determine whether reaginic antibodies from RAO-affected horses have the ability to activate mast cells. These bioassays involved measuring degranulation of rat peritoneal mast cells, activation of NF-κB and morphological changes in basophilic leukemia cells (RBL-2H3) following incubation with horse serum from RAO-affected horses that were sensitive and insensitive to Aspergillus fumigatus (A. fumigatus) or from unaffected horses. Our results show that reaginic antibodies from horses sensitive to A. fumigatus were able to degranulate rat peritoneal mast cells. In additon, there was an increase in the activity of the transcription factor NF-κB in RBL-2H3 cells, and morphological changes were observed in these cells once cross-linking was produced. These findings were not found in horses not sensitive to A. fumigatus and healthy horses. These bioassays demonstrate the ability of reaginic antibodies to stimulate mast cells and indicate that these antibodies could be involved in the

  4. Temperature effects on outpatient visits of respiratory diseases, asthma, and chronic airway obstruction in Taiwan

    NASA Astrophysics Data System (ADS)

    Wang, Yu-Chun; Lin, Yu-Kai

    2014-09-01

    This study evaluated the risk of outpatient visits for respiratory diseases, asthma, and chronic airway obstruction not elsewhere classified (CAO) associated with ambient temperatures and extreme temperature events from 2000 to 2008 in Taiwan. Based on geographical and socioeconomics characteristics, this study divided the whole island into seven areas. A distributed lag non-linear model was used to estimate the area-disease-specific cumulative relative risk (RR), and random-effect meta-analysis was used to estimate the pooled RR of outpatient visits, from lag 0 to lag 7 days, associated with daily temperature, and added effects of prolonged extreme heat and cold for population of all ages, the elderly and younger than 65 years. Pooled analyses showed that younger population had higher outpatient visits for exposing to low temperature of 18 °C, with cumulative 8-day RRs of 1.36 (95 % confidence interval (CI) 1.31-1.42) for respiratory diseases, 1.10 (95 % CI 1.03-1.18) for asthma, and 1.12 (95 % CI 1.02-1.22) for CAO. The elderly was more vulnerable to high temperature of 30 °C with the cumulative 8-day RR of 1.08 (95 % CI 1.03-1.13) for CAO. Elevated outpatient visits for all respiratory diseases and asthma were associated with extreme heat lasting for 6 to 8 days. On the contrary, the extreme cold lasting more than 8 days had significant negative association with outpatient visits of all respiratory diseases. In summary, elderly patients of respiratory diseases and CAO are vulnerable to high temperature. Cold temperature is associated with all types of respiratory diseases for younger patients.

  5. Temperature effects on outpatient visits of respiratory diseases, asthma, and chronic airway obstruction in Taiwan

    NASA Astrophysics Data System (ADS)

    Wang, Yu-Chun; Lin, Yu-Kai

    2015-07-01

    This study evaluated the risk of outpatient visits for respiratory diseases, asthma, and chronic airway obstruction not elsewhere classified (CAO) associated with ambient temperatures and extreme temperature events from 2000 to 2008 in Taiwan. Based on geographical and socioeconomics characteristics, this study divided the whole island into seven areas. A distributed lag non-linear model was used to estimate the area-disease-specific cumulative relative risk (RR), and random-effect meta-analysis was used to estimate the pooled RR of outpatient visits, from lag 0 to lag 7 days, associated with daily temperature, and added effects of prolonged extreme heat and cold for population of all ages, the elderly and younger than 65 years. Pooled analyses showed that younger population had higher outpatient visits for exposing to low temperature of 18 °C, with cumulative 8-day RRs of 1.36 (95 % confidence interval (CI) 1.31-1.42) for respiratory diseases, 1.10 (95 % CI 1.03-1.18) for asthma, and 1.12 (95 % CI 1.02-1.22) for CAO. The elderly was more vulnerable to high temperature of 30 °C with the cumulative 8-day RR of 1.08 (95 % CI 1.03-1.13) for CAO. Elevated outpatient visits for all respiratory diseases and asthma were associated with extreme heat lasting for 6 to 8 days. On the contrary, the extreme cold lasting more than 8 days had significant negative association with outpatient visits of all respiratory diseases. In summary, elderly patients of respiratory diseases and CAO are vulnerable to high temperature. Cold temperature is associated with all types of respiratory diseases for younger patients.

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

    PubMed Central

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

    2016-01-01

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

  7. Reversibility of albuminuria and continuous positive airway pressure compliance in patients of obstructive sleep apnea syndrome.

    PubMed

    Chen, Ning-Hung; Chou, Yu-Ting; Lee, Pei-Hsien; Lin, Shih-Wei; Chuang, Li-Pang; Lin, Yu-Sheng; Yang, Cheng-Ta

    2016-06-01

    A positive correlation between albuminuria and severity of obstructive sleep apnea syndrome (OSAS) has been demonstrated, as indexed by urine albumin-to-creatinine ratios (UACRs). However, the effect of continuous positive airway pressure (CPAP) treatment on albuminuria in OSAS patients has not been established.Sixty subjects, with apnea-hypopnea indices >15 events per hour and no other diagnoses associated with albuminuria, underwent overnight polysomnography for sleep apnea and were examined for UACR at baseline and after 6 months of CPAP therapy. CPAP compliance rates were also recorded.Significant improvement in UACR was found in OSAS patients with good compliance to CPAP treatment after 6 months of therapy (baseline vs 6-month follow-up, 32.0 ± 9.5 vs 19.2 ± 6.5 mg/g, respectively, P = 0.007), whereas slight worsening in UACRs was noted in patients with poor compliance to CPAP treatment (baseline vs 6-month follow-up, respectively, 16.7 ± 4.4 vs 19.1 ± 6.3 mg/g, respectively, P = 0.39). Change in UACR was significant between poor compliance versus good compliance groups (2.4 ± 2.7 vs -12.8 ± 4.4 mg/g, respectively, t = 2.9, P = 0.005). A significant correlation between improvement in UACR and CPAP compliance rates was also noted (Spearman's correlation coefficient: -0.37, P = 0.007). Baseline UACR, good CPAP compliance, and body mass index were independent predictors of changes in UACR.Adequate CPAP treatment improves albuminuria in OSAS patients. In addition to monitoring CPAP adherence and subjective sleepiness, UACR may offer an objective physiological index of CPAP therapeutic effectiveness. PMID:27368036

  8. Reversibility of albuminuria and continuous positive airway pressure compliance in patients of obstructive sleep apnea syndrome

    PubMed Central

    Chen, Ning-Hung; Chou, Yu-Ting; Lee, Pei-Hsien; Lin, Shih-Wei; Chuang, Li-Pang; Lin, Yu-Sheng; Yang, Cheng-Ta

    2016-01-01

    Abstract A positive correlation between albuminuria and severity of obstructive sleep apnea syndrome (OSAS) has been demonstrated, as indexed by urine albumin-to-creatinine ratios (UACRs). However, the effect of continuous positive airway pressure (CPAP) treatment on albuminuria in OSAS patients has not been established. Sixty subjects, with apnea-hypopnea indices >15 events per hour and no other diagnoses associated with albuminuria, underwent overnight polysomnography for sleep apnea and were examined for UACR at baseline and after 6 months of CPAP therapy. CPAP compliance rates were also recorded. Significant improvement in UACR was found in OSAS patients with good compliance to CPAP treatment after 6 months of therapy (baseline vs 6-month follow-up, 32.0 ± 9.5 vs 19.2 ± 6.5 mg/g, respectively, P = 0.007), whereas slight worsening in UACRs was noted in patients with poor compliance to CPAP treatment (baseline vs 6-month follow-up, respectively, 16.7 ± 4.4 vs 19.1 ± 6.3 mg/g, respectively, P = 0.39). Change in UACR was significant between poor compliance versus good compliance groups (2.4 ± 2.7 vs −12.8 ± 4.4 mg/g, respectively, t = 2.9, P = 0.005). A significant correlation between improvement in UACR and CPAP compliance rates was also noted (Spearman's correlation coefficient: −0.37, P = 0.007). Baseline UACR, good CPAP compliance, and body mass index were independent predictors of changes in UACR. Adequate CPAP treatment improves albuminuria in OSAS patients. In addition to monitoring CPAP adherence and subjective sleepiness, UACR may offer an objective physiological index of CPAP therapeutic effectiveness. PMID:27368036

  9. Characterisation of Brachycephalic Obstructive Airway Syndrome in French Bulldogs Using Whole-Body Barometric Plethysmography.

    PubMed

    Liu, Nai-Chieh; Sargan, David R; Adams, Vicki J; Ladlow, Jane F

    2015-01-01

    Brachycephalic obstructive airway syndrome (BOAS) is an important health and welfare problem in several popular dog breeds. Whole-body barometric plethysmography (WBBP) is a non-invasive method that allows safe and repeated quantitative measurements of respiratory cycles on unsedated dogs. Here respiratory flow traces in French bulldogs from the pet population were characterised using WBBP, and a computational application was developed to recognise affected animals. Eighty-nine French bulldogs and twenty non-brachycephalic controls underwent WBBP testing. A respiratory functional grading system was used on each dog based on respiratory signs (i.e. respiratory noise, effort, etc.) before and after exercise. For development of an objective BOAS classifier, functional Grades 0 and I were considered to have insignificant clinical signs (termed here BOAS-) and Grades II and III to have significant signs (termed here BOAS+). A comparison between owner-perception of BOAS and functional grading revealed that 60 % of owners failed to recognise BOAS in dogs that graded BOAS+ in this study.WBBP flow traces were found to be significantly different between non-brachycephalic controls and Grade 0 French bulldogs; BOAS- and BOAS+ French bulldogs. A classifier was developed using quadratic discriminant analysis of the respiratory parameters to distinguish BOAS- and BOAS + French bulldogs, and a BOAS Index was calculated for each dog. A cut-off value of the BOAS Index was selected based on a receiver operating characteristic (ROC) curve. Sensitivity, specificity, positive predictive value, and negative predictive value of the classifier on the training group (n=69) were 0.97, 0.93, 0.95, and 0.97, respectively. The classifier was validated using a test group of French bulldogs (n=20) with an accuracy of 0.95. WBBP offers objective screening for the diagnosis of BOAS in French Bulldogs. The technique may be applied to other brachycephalic breeds affected by BOAS, and possibly to

  10. Neutrophil and macrophage apoptosis in bronchoalveolar lavage fluid from healthy horses and horses with recurrent airway obstruction (RAO)

    PubMed Central

    2014-01-01

    Background Dysregulation of apoptosis has been implicated in a range of diseases including tumors, neurodegenerative and autoimmine diseases, as well as allergic asthma and chronic obstructive pulmonary disease (COPD) in humans. Although it has a different pathophysiology, delayed apoptosis of various inflammatory cells may play a pivotal role in the development of recurrent airway obstruction (RAO) in horses. Reduction of inflammatory cell apoptosis or a dysregulation of this process could lead to chronic inflammation and tissue injury. Therefore, the aim of this study was to investigate the rate of apoptosis and necrosis of neutrophils and macrophages in bronchoalveolar lavage fluid obtained from seven horses suffering from RAO (study group) and seven control horses. Results We demonstrated that neutrophil/macrophage apoptosis is altered in RAO-affected horses compared with the control group in the BAL fluid. We found a significant difference between the median percentage of early and late apoptosis of neutrophils between the study and control group of horses. Moreover, we found a positive correlation between the rate of apoptosis and the median percentage of macrophages in RAO-affected horses. Conclusion The findings suggest that apoptosis dysregulation may play a significant role in the pathogenesis of RAO. However, further studies are needed to clarify the role of altered apoptosis in the course of equine recurrent airway obstruction. PMID:24460911

  11. Computational fluid dynamics modeling of the upper airway of children with obstructive sleep apnea syndrome in steady flow.

    PubMed

    Xu, Chun; Sin, SangHun; McDonough, Joseph M; Udupa, Jayaram K; Guez, Allon; Arens, Raanan; Wootton, David M

    2006-01-01

    Computational fluid dynamic (CFD) analysis was used to model the effect of airway geometry on internal pressure in the upper airway of three children with obstructive sleep apnea syndrome (OSAS), and three controls. Model geometry was reconstructed from magnetic resonance images obtained during quiet tidal breathing, meshed with an unstructured grid, and solved at normative peak resting flow. The unsteady Reynolds-averaged Navier-Stokes equations were solved with steady flow boundary conditions in inspiration and expiration, using a two-equation low-Reynolds number turbulence model. Model results were validated using an in-vitro scale model, unsteady flow simulation, and reported nasal resistance measurements in children. Pharynx pressure drop strongly correlated to airway area restriction. Inspiratory pressure drop was primarily proportional to the square of flow, consistent with pressure losses due to convective acceleration caused by area restriction. On inspiration, in OSAS pressure drop occurred primarily between the choanae and the region where the adenoids overlap the tonsils (overlap region) due to airway narrowing, rather than in the nasal passages; in controls the majority of pressure drop was in the nasal passages. On expiration, in OSAS the majority of pressure drop occurred between the oropharynx (posterior to the tongue) and overlap region, and local minimum pressure in the overlap region was near atmospheric due to pressure recovery in the anterior nasopharynx. The results suggest that pharyngeal airway shape in children with OSAS significantly affects internal pressure distribution compared to nasal resistance. The model may also help explain regional dynamic airway narrowing during expiration. PMID:16098533

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

    PubMed

    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

    2016-04-01

    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

  13. 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

  14. Established vascular effects of continuous positive airway pressure therapy in patients with obstructive sleep apnoea—an update

    PubMed Central

    Wons, Annette Marie

    2015-01-01

    The aim of this review was to summarize the current data from randomised controlled trials (RCTs) on vascular effects of continuous positive airway pressure (CPAP) therapy in patients with obstructive sleep apnoea (OSA). There is good evidence from RCTs that CPAP lowers blood pressure (BP) to a clinically significant amount. The effect seems to be dependent on the hours of nightly CPAP usage. Data from RCTs have also proven a beneficial effect of CPAP on measures of vascular function such as endothelial function and arterial stiffness. However, there is still a lack of evidence from RCTs proving that CPAP reduces vascular events and mortality. PMID:26101649

  15. [Changes in the upper airway in patients with sleep obstructive apnea and/or chronic snoring treated with mandibular appliances].

    PubMed

    Cobo, J; de Carlos, F; Díaz Esnal, B; Fernández, M P; Llorente, S; Llorente, J

    2001-01-01

    We have analysed the possible modifications in the upper airways (UA) of the lateral cranial teleradiography in 25 adult males with Obstructive Sleep Apnea (OSAS) and/or chronic snoring, with dental and squeletal Class I, treated with advance mandibular appliances (MAD). Results of our study showed a clear increase of the UA in the oropharynx in all the subjects studied. The study of the changes in the UA using the lateral cranial teleradiography in order to evaluate the effectiveness of the MAD can contribute to consider its effectiveness in the cases with OSAS when they are indicated. However it will be needed to contrast these results with polisomnography. PMID:11692961

  16. Genome-Wide Association Study Identification of Novel Loci Associated with Airway Responsiveness in Chronic Obstructive Pulmonary Disease.

    PubMed

    Hansel, Nadia N; Paré, Peter D; Rafaels, Nicholas; Sin, Don D; Sandford, Andrew; Daley, Denise; Vergara, Candelaria; Huang, Lili; Elliott, W Mark; Pascoe, Chris D; Arsenault, Bryna A; Postma, Dirkje S; Boezen, H Marike; Bossé, Yohan; van den Berge, Maarten; Hiemstra, Pieter S; Cho, Michael H; Litonjua, Augusto A; Sparrow, David; Ober, Carole; Wise, Robert A; Connett, John; Neptune, Enid R; Beaty, Terri H; Ruczinski, Ingo; Mathias, Rasika A; Barnes, Kathleen C

    2015-08-01

    Increased airway responsiveness is linked to lung function decline and mortality in subjects with chronic obstructive pulmonary disease (COPD); however, the genetic contribution to airway responsiveness remains largely unknown. A genome-wide association study (GWAS) was performed using the Illumina (San Diego, CA) Human660W-Quad BeadChip on European Americans with COPD from the Lung Health Study. Linear regression models with correlated meta-analyses, including data from baseline (n = 2,814) and Year 5 (n = 2,657), were used to test for common genetic variants associated with airway responsiveness. Genotypic imputation was performed using reference 1000 Genomes Project data. Expression quantitative trait loci (eQTL) analyses in lung tissues were assessed for the top 10 markers identified, and immunohistochemistry assays assessed protein staining for SGCD and MYH15. Four genes were identified within the top 10 associations with airway responsiveness. Markers on chromosome 9p21.2 flanked by LINGO2 met a predetermined threshold of genome-wide significance (P < 9.57 × 10(-8)). Markers on chromosomes 3q13.1 (flanked by MYH15), 5q33 (SGCD), and 6q21 (PDSS2) yielded suggestive evidence of association (9.57 × 10(-8) < P ≤ 4.6 × 10(-6)). Gene expression studies in lung tissue showed single nucleotide polymorphisms on chromosomes 5 and 3 to act as eQTL for SGCD (P = 2.57 × 10(-9)) and MYH15 (P = 1.62 × 10(-6)), respectively. Immunohistochemistry confirmed localization of SGCD protein to airway smooth muscle and vessels and MYH15 to airway epithelium, vascular endothelium, and inflammatory cells. We identified novel loci associated with airway responsiveness in a GWAS among smokers with COPD. Risk alleles on chromosomes 5 and 3 acted as eQTLs for SGCD and MYH15 messenger RNA, and these proteins were expressed in lung cells relevant to the development of airway responsiveness. PMID:25514360

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

    PubMed Central

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

    2016-01-01

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

  18. Sensorimotor function of the upper-airway muscles and respiratory sensory processing in untreated obstructive sleep apnea.

    PubMed

    Eckert, Danny J; Lo, Yu L; Saboisky, Julian P; Jordan, Amy S; White, David P; Malhotra, Atul

    2011-12-01

    Numerous studies have demonstrated upper-airway neuromuscular abnormalities during wakefulness in snorers and obstructive sleep apnea (OSA) patients. However, the functional role of sensorimotor impairment in OSA pathogenesis/disease progression and its potential effects on protective upper-airway reflexes, measures of respiratory sensory processing, and force characteristics remain unclear. This study aimed to gain physiological insight into the potential role of sensorimotor impairment in OSA pathogenesis/disease progression by comparing sensory processing properties (respiratory-related evoked potentials; RREP), functionally important protective reflexes (genioglossus and tensor palatini) across a range of negative pressures (brief pulses and entrained iron lung ventilation), and tongue force and time to task failure characteristics between 12 untreated OSA patients and 13 controls. We hypothesized that abnormalities in these measures would be present in OSA patients. Upper-airway reflexes (e.g., genioglossus onset latency, 20 ± 1 vs. 19 ± 2 ms, P = 0.82), early RREP components (e.g., P1 latency 25 ± 2 vs. 25 ± 1 ms, P = 0.78), and the slope of epiglottic pressure vs. genioglossus activity during iron lung ventilation (-0.68 ± 1.0 vs. -0.80 ± 2.0 cmH(2)O/%max, P = 0.59) were not different between patients and controls. Maximal tongue protrusion force was greater in OSA patients vs. controls (35 ± 2 vs. 27 ± 2 N, P < 0.01), but task failure occurred more rapidly (149 ± 24 vs. 254 ± 23 s, P < 0.01). Upper-airway protective reflexes across a range of negative pressures as measured by electromyography and the early P1 component of the RREP are preserved in OSA patients during wakefulness. Consistent with an adaptive training effect, tongue protrusion force is increased, not decreased, in untreated OSA patients. However, OSA patients may be vulnerable to fatigue of upper-airway dilator muscles, which could contribute to disease progression. PMID:21885797

  19. IL-13-producing BLT1-positive CD8 cells are increased in asthma and are associated with airway obstruction

    PubMed Central

    Dakhama, Azzeddine; Collins, Maureen L.; Ohnishi, Hiroshi; Goleva, Elena; Leung, Donald Y. M.; Alam, Rafeul; Sutherland, E. Rand; Martin, Richard J.; Gelfand, Erwin W.

    2013-01-01

    Background The role of CD8 T lymphocytes in the pathogenesis of asthma is not well understood. We investigated whether a subset of IL-13-producing BLT1-positive CD8 T lymphocytes is present in asthmatic airways and is associated with impaired lung function. Methods Bronchoalveolar lavage (BAL) cells were obtained from asthmatic (n=39) and healthy control (n=28) subjects. Cells were stimulated with phorbol ester and ionomycin in the presence of brefeldin A and stained for CD8, BLT1 and intracellular IL-13. The frequency of IL-13-producing BLT1-positive CD8 T lymphocytes was compared between the two groups and related to lung function, serum IgE levels and reticular basement membrane (RBM) thickness. Results A subset of CD8 T lymphocytes expressing BLT1 and producing IL-13 was detected in the airways of all asthmatic subjects. The frequency of this subset among recovered lymphocytes was significantly higher in the airways of asthmatic subjects compared to controls (mean ± SEM: 16.2 ± 1.4 vs. 5.3 ± 0.5, respectively, p < 0.001), and correlated positively with serum IgE levels and RBM thickness. More importantly, the frequency of CD8 T lymphocytes co-expressing BLT1 and IL-13 was inversely related to FEV1 and FEF[25-75] percent predicted values (p<0.001). Conclusions A subset of CD8 T lymphocytes expressing BLT1 and producing IL-13 is present in the airways of asthmatics. The accumulation of these cells is associated with airway obstruction, suggesting that they may play a significant pathogenic role in bronchial asthma. PMID:23573812

  20. Cigarette smoke and calcium conspire to impair CFTR function in airway epithelia.

    PubMed

    Braun, Andrew P

    2014-01-01

    To maintain health and function in response to inhaled environmental irritants and toxins, the lungs and airways depend upon an innate defense system that involves the secretion of mucus (i.e., mucin, salts, and water) by airway epithelium onto the apical surface to trap foreign particles. Airway mucus is then transported in an oral direction via ciliary beating and coughing, which helps to keep the airways clear. CFTR (cystic fibrosis transmembrane conductance regulator) is a cAMP-regulated Cl(-) channel in the apical membrane of epithelium that contributes to salt and water secretion onto the luminal surface of airways, thereby ensuring that secreted mucus is sufficiently hydrated for movement along the epithelial surface. Dehydration of airway mucus, as occurs in cystic fibrosis, results in a more viscous, less mobile secretion that compromises the lung’s innate defense system by facilitating a build-up of foreign particles and bacterial growth. Related to this situation is chronic obstructive pulmonary disease (COPD), which is a leading cause of death globally. A major cause of COPD is cigarette smoking, which has been reported to decrease the cellular levels of CFTR in airway epithelia. In their recent article, Rasmussen and coworkers now report that exposure to cigarette smoke elevates cytosolic free Ca(2+) in airway epithelium, leading to decreased surface localization and cellular expression of CFTR and reduced levels of secreted airway surface liquid. Blocking this increase in cytosolic Ca(2+) largely prevented CFTR loss in airway epithelium and surprisingly, cellular lysosomes appear to be a major source for smoke-induced Ca(2+) elevation. PMID:24755862

  1. Upper Airway Resistance Syndrome Patients Have Worse Sleep Quality Compared to Mild Obstructive Sleep Apnea

    PubMed Central

    de Godoy, Luciana Balester Mello; Luz, Gabriela Pontes; Palombini, Luciana Oliveira; e Silva, Luciana Oliveira; Hoshino, Wilson; Guimarães, Thaís Moura; Tufik, Sergio; Bittencourt, Lia; Togeiro, Sonia Maria

    2016-01-01

    Purpose To compare sleep quality and sustained attention of patients with Upper Airway Resistance Syndrome (UARS), mild Obstructive Sleep Apnea (OSA) and normal individuals. Methods UARS criteria were presence of excessive daytime sleepiness (Epworth Sleepiness Scale—ESS—≥ 10) and/or fatigue (Modified Fatigue Impact Scale—MFIS—≥ 38) associated to Apnea/hypopnea index (AHI) ≤ 5 and Respiratory Disturbance Index (RDI) > 5 events/hour of sleep or more than 30% of total sleep time with flow limitation. Mild OSA was considered if the presence of excessive daytime sleepiness (ESS ≥ 10) and/or fatigue (MFIS ≥ 38) associated to AHI ≥ 5 and ≤ 15 events/hour. “Control group” criteria were AHI < 5 events/hour and RDI ≤ 5 events/hour and ESS ≤ 9, without any sleep, clinical, neurological or psychiatric disorder. 115 individuals (34 UARS and 47 mild OSA patients and 34 individuals in “control group”), adjusted for age, gender, body mass index (BMI) and schooling years, performed sleep questionnaires and sustained attention evaluation. Psychomotor Vigilance Task (PVT) was performed five times (each two hours) from 8 a.m. to 4 p.m. Results UARS patients had worse sleep quality (Functional Outcomes of Sleep Questionnaire—FOSQ—and Pittsburgh Sleep Quality Index—PSQI: p < 0.05) and more fatigue than mild OSA patients (p = 0.003) and scored significantly higher in both Beck inventories than “control group” (p < 0.02). UARS patients had more lapses early in the morning (in time 1) compared to the results in the afternoon (time 5) than mild OSA (p = 0.02). Mild OSA patients had more lapses in times 2 than in time 5 compared to “control group” (p = 0.04). Conclusions UARS patients have a worse sleep quality, more fatigue and a worse early morning sustained attention compared to mild OSA. These last had a worse sustained attention than controls. PMID:27228081

  2. Excessive variations in the plethysmographic waveform during spontaneous ventilation: an important sign of upper airway obstruction.

    PubMed

    Perel, Azriel

    2014-12-01

    The respiratory variations in the plethysmographic (PLET) waveform of the pulse oximeter during mechanical ventilation can be automatically quantified as the PLET variation index (PVI(®)). Like other dynamic variables, the PVI may provide useful information about fluid responsiveness but only when the patient is receiving fully controlled mechanical ventilation with no spontaneous breathing activity. However, a growing number of monitors that automatically measure and display the values of the PVI and other dynamic variables are being introduced into clinical practice. Using these monitors in spontaneously breathing patients may cause inadequately trained personnel to make erroneous decisions or may eventually lead to a total disregard of dynamic parameters altogether. The aim of this study is to call attention to the fact that excessive variations in the PVI during spontaneous ventilation, termed sPVI, should not be regarded as artifactual since they may be an early important sign of upper airway obstruction (UAO). Among the monitor screen shots that were stored for educational purposes, I have identified 4 screen shots of patients who were clinically diagnosed as having significant UAO. In all instances, UAO was associated with prominent variations in the PLET waveform. These variations were calculated as the difference between the maximal and minimal amplitudes of the PLET signal divided by either the maximal amplitude (sPVI) or by the mean of the 2 values (ΔPOP). The ranges of the measured ΔPOP and sPVI values during UAO were 28% to 42% and 25% to 39%, respectively. These values are 2 to 3 times higher than the range of 9.5% to 15% that was repeatedly found as the best threshold for the identification of fluid responsiveness in mechanically ventilated patients. In 2 of these cases, simultaneously measured values of the pulse pressure variation were high as well (19% and 34%), while the calculated pulsus paradoxus was 28 and 40 mm Hg. In 2 cases, the analog

  3. The effect of obstructive sleep apnea and treatment with continuous positive airway pressure on stroke rehabilitation: rationale, design and methods of the TOROS study

    PubMed Central

    2014-01-01

    Background Obstructive sleep apnea is a common sleep disorder in stroke patients. Obstructive sleep apnea is associated with stroke severity and poor functional outcome. Continuous positive airway pressure seems to improve functional recovery in stroke rehabilitation. To date, the effect of continuous positive airway pressure on cognitive functioning in stroke patients is not well established. The current study will investigate the effectiveness of continuous positive airway pressure on both cognitive and functional outcomes in stroke patients with obstructive sleep apnea. Methods/Design A randomized controlled trial will be conducted on the neurorehabilitation unit of Heliomare, a rehabilitation center in the Netherlands. Seventy stroke patients with obstructive sleep apnea will be randomly allocated to an intervention or control group (n = 2×35). The intervention will consist of four weeks of continuous positive airway pressure treatment. Patients allocated to the control group will receive four weeks of treatment as usual. Outcomes will be assessed at baseline, immediately after the intervention and at two-month follow-up. In a supplementary study, these 70 patients with obstructive sleep apnea will be compared to 70 stroke patients without obstructive sleep apnea with respect to cognitive and functional status at rehabilitation admission. Additionally, the societal participation of both groups will be assessed at six months and one year after inclusion. Discussion This study will provide novel information on the effects of obstructive sleep apnea and its treatment with continuous positive airway pressure on rehabilitation outcomes after stroke. Trial registration Trial registration number: Dutch Trial Register NTR3412 PMID:24568360

  4. Sensory neuropeptides and airway function.

    PubMed

    Solway, J; Leff, A R

    1991-12-01

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

  5. The Relationship of Mucus Concentration (Hydration) to Mucus Osmotic Pressure and Transport in Chronic Bronchitis

    PubMed Central

    Coakley, Raymond D.; Button, Brian; Henderson, Ashley G.; Zeman, Kirby L.; Alexis, Neil E.; Peden, David B.; Lazarowski, Eduardo R.; Davis, C. William; Bailey, Summer; Fuller, Fred; Almond, Martha; Qaqish, Bahjat; Bordonali, Elena; Rubinstein, Michael; Bennett, William D.; Kesimer, Mehmet; Boucher, Richard C.

    2015-01-01

    Rationale: Chronic bronchitis (CB) is characterized by persistent cough and sputum production. Studies were performed to test whether mucus hyperconcentration and increased partial osmotic pressure, in part caused by abnormal purine nucleotide regulation of ion transport, contribute to the pathogenesis of CB. Objectives: We tested the hypothesis that CB is characterized by mucus hyperconcentration, increased mucus partial osmotic pressures, and reduced mucus clearance. Methods: We measured in subjects with CB as compared with normal and asymptomatic smoking control subjects indices of mucus concentration (hydration; i.e., percentage solids) and sputum adenine nucleotide/nucleoside concentrations. In addition, sputum partial osmotic pressures and mucus transport rates were measured in subjects with CB. Measurements and Results: CB secretions were hyperconcentrated as indexed by an increase in percentage solids and total mucins, in part reflecting decreased extracellular nucleotide/nucleoside concentrations. CB mucus generated concentration-dependent increases in partial osmotic pressures into ranges predicted to reduce mucus transport. Mucociliary clearance (MCC) in subjects with CB was negatively correlated with mucus concentration (percentage solids). As a test of relationships between mucus concentration and disease, mucus concentrations and MCC were compared with FEV1, and both were significantly correlated. Conclusions: Abnormal regulation of airway surface hydration may slow MCC in CB and contribute to disease pathogenesis. PMID:25909230

  6. Oxidative stress and quality of life in elderly patients with obstructive sleep apnea syndrome: are there differences after six months of Continuous Positive Airway Pressure treatment?

    PubMed Central

    Yagihara, Fabiana; Lucchesi, Ligia Mendonça; D'Almeida, Vânia; de Mello, Marco Túlio; Tufik, Sergio; Bittencourt, Lia Rita Azeredo

    2012-01-01

    OBJECTIVES: This study evaluated the effect of Continuous Positive Airway Pressure treatment on oxidative stress parameters and the quality of life of elderly patients with obstructive sleep apnea syndrome. METHODS: In total, 30 obstructive sleep apnea syndrome patients and 27 subjects without obstructive sleep apnea syndrome were included in this study. Both groups underwent quality of life and oxidative stress evaluations at baseline and after six months. Polysomnography was performed in both groups at baseline and a second time in the obstructive sleep apnea syndrome group after six months of Continuous Positive Airway Pressure treatment. All of the variables were compared between the control and obstructive sleep apnea syndrome groups in this prospective case-control study. RESULTS: The baseline concentrations of the antioxidant enzyme catalase were higher in the obstructive sleep apnea syndrome group than the control group. After Continuous Positive Airway Pressure treatment, the obstructive sleep apnea syndrome group exhibited a reduction in the level of oxidative stress, as indicated by a decrease in the level of lipid peroxidation measured by the malondialdehyde (MDA) concentration [pre: 2.7 nmol malondialdehyde/mL (95% 1.6-3.7) vs. post: 1.3 nmol MDA/mL (0.7-1.9), p<0.01]. Additionally, improvements were observed in two domains covered by the SF-36 questionnaire: functional capacity [pre: 77.4 (69.2-85.5) vs. post: 83.4 (76.9-89.9), p = 0.002] and pain [pre: 65.4 (52.8-78.1) vs. post: 77.8 (67.2-88.3), p = 0.004]. CONCLUSION: Our study demonstrated that the use of Continuous Positive Airway Pressure to treat obstructive sleep apnea syndrome in elderly patients reduced oxidative stress and improved the quality of life. PMID:22760893

  7. Detection of changes in respiratory mechanics due to increasing degrees of airway obstruction in asthma by the forced oscillation technique.

    PubMed

    Cavalcanti, Juliana V; Lopes, Agnaldo J; Jansen, José M; Melo, Pedro L

    2006-12-01

    Forced expiratory airflows and volumes are often used to assess the airway obstruction in asthmatics. However, forced maneuvers may change bronchial tone and modify airway patency. The aim of this study was to determine whether the Forced Oscillation Technique (FOT), which does not require forced manoeuvres, may be useful to describe the changes in respiratory mechanics in progressive asthma. This study involved 25 healthy and 84 asthmatics, including patients with normal spirometric exam (NE), mild moderate and severe obstruction. Resistive data were interpreted using the respiratory system resistance extrapolated at 0 Hz (R0), the mean respiratory resistance (Rm), and the resistance/frequency slope (S). Reactance data were interpreted by its mean values (Xm), the dynamic compliance (Crs,dyn), and resonant frequency (fr). Receiver operating characteristics curves were used to determine the sensitivity (Se) and specificity (Sp) of FOT parameters in identifying asthma. There were not statistically significant differences between the control and NE groups. Comparing the control and mild groups, significant increases of R0 (P<0.0007), Rm (P<0.003), and S (P<0.003) were observed. In reactive parameters, a significant reduction in Crs,dyn (P<0.04) was observed, while Xm and fr presented significant increases (P<0.0007 and P<0.006, respectively). Comparison between mild and moderate groups showed non-significant modifications in all of the parameters, except for Xm (P<0.02). In the late stages (moderate to severe obstruction), all of the resistive parameters, as well as the reactive ones Xm (P<0.007) and Crs,dyn (P<0.03), presented statistically significant modifications. Among the studied parameters, the effects of airway obstruction in asthma seem to be well described by R0, Rm, S and Xm, which were in close agreement with physiological fundamentals. The best parameters for detecting asthma were R0 (Se=81%, Sp=76%), S (Se=78%, Sp=72%) and Xm (Se=81%, Sp=80%). In

  8. Expression of surface platelet receptors (CD62P and CD41/61) in horses with recurrent airway obstruction (RAO).

    PubMed

    Iwaszko-Simonik, Alicja; Niedzwiedz, Artur; Graczyk, Stanislaw; Slowikowska, Malwina; Pliszczak-Krol, Aleksandra

    2015-03-15

    Recurrent airway obstruction (RAO) is an allergic disease of horses similar to human asthma, which is characterized by airway inflammation and activation of neutrophils, lymphocytes and platelets. Platelet activation and an increase in circulating platelet-leukocyte aggregates may lead to airway remodeling. The aim of this study was to investigate platelet status in RAO-affected horses based on the platelet morphology and platelet surface expression of CD41/61 and CD62P. Ten RAO-affected horses and ten healthy horses were included in this study. Blood samples were obtained to determine the platelet count (PLT), mean platelet volume (MPV) and platelet large cell ratio (P-LCR). Expression of CD62P and CD41/61 was detected by flow cytometry on activated platelets. The median PLT was significantly reduced in horses with RAO compared to the controls. The MPV and the P-LCR values were significantly higher in RAO horses than controls. Expression of CD41/61 on platelets was increased in RAO horses, while CD62P expression was reduced. This study demonstrated the morphological changes in platelets and expression of platelet surface receptors. Despite the decrease of CD62P expression, the observed increased surface expression of CD41/61 on platelets in horses with RAO may contribute to the formation of platelet aggregates in their respiratory system. PMID:25665521

  9. Long-Term Continuous Positive Airway Pressure Therapy Normalizes High Exhaled Nitric Oxide Levels in Obstructive Sleep Apnea

    PubMed Central

    Chua, Ai-Ping; Aboussouan, Loutfi S.; Minai, Omar A.; Paschke, Kelly; Laskowski, Daniel; Dweik, Raed A.

    2013-01-01

    Study Objectives: Upper airway inflammation and oxidative stress have been implicated in the pathogenesis of obstructive sleep apnea (OSA) and may be linked to cardiovascular consequences. We prospectively examined fraction of exhaled nitric oxide (FENO), a surrogate marker of upper airway inflammation using a portable nitric oxide analyzer (NIOX MINO). Design: In consecutive adult nonsmokers with suspected OSA, FENO was measured immediately before and after polysomnographic studies, and within 1-3 months following continuous positive airway pressure (CPAP) therapy. Measurement and Results: FENO levels were increased in the 75 patients with OSA compared to the 29 controls, both before sleep (13.4 ± 6.5 ppb vs. 6.5 ± 3.5; p < 0.001) and after sleep (19.0 ± 7.7 ppb vs. 6.9 ± 3.7; p < 0.001). Furthermore, in patients with OSA, FENO levels were significantly higher post-sleep than pre-sleep (19.0 ± 7.7 ppb vs. 13.4 ± 6.5; p < 0.001), while there was no significant overnight change in patients without OSA. The rise in FENO correlated with the apnea-hypopnea index (r = 0.65, p < 0.001), nadir oxygen saturation (r = 0.54, p < 0.001), and arousal index (r = 0.52, p < 0.001). Thirty-seven of these patients underwent CPAP titration and treatment. Successful titration was associated with a lower overnight increase in FENO (7.2 ± 3.3 vs. 11.0 ± 4.3, p = 0.02). FENO levels declined after 1-3 months of CPAP therapy (11.7 ± 4.4 ppb, p < 0.001). Conclusions: FENO levels are elevated in OSA, correlate with severity, and decrease after positive pressure therapy. This study supports the role of upper airway inflammation in OSA pathogenesis and a possible role for FENO in monitoring CPAP therapy. Citation: Chua AP; Aboussouan LS; Minai OA; Paschke K; Laskowski D; Dweik RA. Long-term continuous positive airway pressure therapy normalizes high exhaled nitric oxide levels in obstructive sleep apnea. J Clin Sleep Med 2013;9(6):529-535. PMID:23772184

  10. Modafinil Increases Awake EEG Activation and Improves Performance in Obstructive Sleep Apnea during Continuous Positive Airway Pressure Withdrawal

    PubMed Central

    Wang, David; Bai, Xiao Xue; Williams, Shaun C.; Hua, Shu Cheng; Kim, Jong-Won; Marshall, Nathaniel S.; D'Rozario, Angela; Grunstein, Ronald R.

    2015-01-01

    Objectives: We examined the changes in waking electroencephalography (EEG) biomarkers with modafinil during continuous positive airway pressure (CPAP) withdrawal in patients with obstructive sleep apnea (OSA) to investigate neurophysiological evidence for potential neurocognitive improvements. Design: Randomized double-blind placebo-controlled crossover study. CPAP was used for the first night and then withdrawn for 2 subsequent nights. Each morning after the 2 CPAP withdrawal nights, patients received either 200 mg modafinil or placebo. After a 5-w washout, the procedure repeated with the crossover drug. Setting: University teaching hospital. Participants: Stable CPAP users (n = 23 men with OSA) Measurement and Results: Karolinska Drowsiness Test (KDT) (awake EEG measurement with eyes open and closed), Psychomotor Vigilance Task (PVT), and driving simulator Performance were assessed bihourly during the 3 testing days following CPAP treatment and CPAP withdrawal nights. Compared to placebo, modafinil significantly increased awake EEG activation (faster EEG frequency) with increased alpha/delta (A/D) ratio (P < 0.0001) and fast ratio = (alpha+beta)/(delta+theta) (P < 0.0001) across the 2 days of CPAP withdrawal. The A/D ratio significantly correlated with the driving simulator response time (P = 0.015), steering variation (P = 0.002), and PVT reaction time (P = 0.006). In contrast, individual EEG band power of alpha, beta, theta, and delta did not correlate with any neurocognitive performance. Conclusions: Modafinil administration during continuous positive airway pressure (CPAP) withdrawal increased awake EEG activation, which correlated to improved performance. This study provides supporting neurophysiological evidence that modafinil is a potential short-term treatment option during acute CPAP withdrawal. Citation: Wang D, Bai XX, Williams SC, Hua SC, Kim JW, Marshall NS, D'Rozario A, Grunstein RR. Modafinil increases awake EEG activation and improves performance

  11. Relationship between surface tension of upper airway lining liquid and upper airway collapsibility during sleep in obstructive sleep apnea hypopnea syndrome.

    PubMed

    Kirkness, Jason P; Madronio, Melanie; Stavrinou, Rosie; Wheatley, John R; Amis, Terence C

    2003-11-01

    Lowering surface tension (gamma) of upper airway lining liquid (UAL) reduces upper airway opening (anesthetized humans) and closing (anesthetized rabbits) pressures. We now hypothesize that in sleeping obstructive sleep apnea hypopnea syndrome (OSAHS) patients lowering gamma of UAL will enhance upper airway stability and decrease the severity of sleep-disordered breathing. Nine OSAHS patients [respiratory disturbance index (RDI): 49 +/- 8 (SE) events/h, diagnostic night] participated in a two-part, one-night, polysomnography study. In the first part, upper airway closing pressures (during non-rapid eye movement sleep, Pcrit) were measured and samples of UAL (awake) were obtained before and after 2.5 ml of surfactant (Exosurf, Glaxo Smith Kline) was instilled into the posterior pharynx. The gamma of UAL was determined with the use of the "pull-off" force technique. In the second part, subjects received a second application of 2.5 ml of surfactant and then slept the remainder of the night (205 +/- 30 min). Instillation of surfactant decreased the gamma of UAL from 60.9 +/- 3.1 mN/m (control) to 45.2 +/- 2.5 mN/m (surfactant group) (n = 9, P < 0.001). Pcrit decreased from 1.19 +/- 1.14 cmH2O (control) to -0.56 +/- 1.15 cmH2O (surfactant group) (n = 7, P < 0.02). Compared with the second half of diagnostic night, surfactant decreased RDI from 51 +/- 8 to 35 +/- 8 events/h (n = 9, P < 0.03). The fall in RDI (deltaRDI) correlated with the fall in gamma of UAL (deltagamma) (deltaRDI = 1.8 x deltagamma, r = 0.68, P = 0.04). Hypopneas decreased approximately 50% from 42 +/- 8 to 20 +/- 5 events/h (n = 9, P < 0.03, paired t-test). The gamma of UAL measured the next morning remained low at 49.5 +/- 2.7 mN/m (n = 9, P < 0.001, ANOVA, compared with control). In conclusion, instillation of surfactant reduced the gamma of UAL in OSAHS patients and decreased Pcrit and the occurrence of hypopneas. Therapeutic manipulation of gamma of UAL may be beneficial in reducing the severity

  12. Consequences of Obstructive Sleep Apnea: Cardiovascular Risk of Obstructive Sleep Apnea and Whether Continuous Positive Airway Pressure Reduces that Risk.

    PubMed

    Khayat, Rami; Pleister, Adam

    2016-09-01

    Obstructive sleep apnea (OSA) is present in up to 25% of otherwise healthy individuals. OSA is associated with intermittent hypoxia, oxidative stress, sympathetic activation, and an inflammatory response. These perturbations mediate the role of OSA as an independent and modifiable risk factor for cardiovascular disease (CVD). OSA can induce CVD or accelerate the progression of CVD into an end-stage disorder, including heart failure and stroke. Current clinical recommendations are based on existing clinical trial data and the clinical experience of our program; current and future clinical trials will help to optimize management of OSA in the setting of CVD. PMID:27542874

  13. Pilot Study of Nasal Expiratory Positive Airway Pressure Devices for the Treatment of Childhood Obstructive Sleep Apnea Syndrome

    PubMed Central

    Kureshi, Suraiya A.; Gallagher, Paul R.; McDonough, Joseph M.; Cornaglia, Mary Anne; Maggs, Jill; Samuel, John; Traylor, Joel; Marcus, Carole L.

    2014-01-01

    Study Objectives: Alternative therapies for childhood obstructive sleep apnea syndrome (OSAS) are needed as OSAS may persist despite adenotonsillectomy, and continuous positive airway pressure (CPAP) adherence is low. Nasal expiratory positive airway pressure (NEPAP) devices have not been studied in children. We hypothesized that NEPAP would result in polysomnographic improvement. Further, we aimed to determine NEPAP adherence, effects on sleepiness, behavior, and quality of life. Methods: A randomized, double-blind, placebo-controlled, crossover pilot study was performed. CPAP candidates, 8-16 years old, underwent NEPAP and placebo polysomnograms. Subjects with ≥ 50% reduction in the apnea hypopnea index (AHI) from placebo to NEPAP night or AHI < 5/h on NEPAP night wore NEPAP at home for 30 days. Adherence was assessed by daily phone calls/emails and collecting used devices. Results: Fourteen subjects (age 13.4 ± 1.9 years, BMI z-scores 2.2 ± 1 [mean ± SD]) were studied. There was significant improvement in the obstructive apnea index with NEPAP vs. placebo: 0.6 (0-21.1)/h vs. 4.2 (0-41.9)/h (median [range], p = 0.010) and trends for improvement in other polysomnographic parameters. However, responses were variable, with 3 subjects not improving and 2 worsening. Older children and those with less hypercapnia had a better response. Eight subjects were sent home with devices; one was lost to follow-up, and adherence in the remainder was 83% of nights; these subjects had a significant improvement in sleepiness and quality of life. Conclusions: NEPAP devices are a potential alternative therapy for OSAS in a small subset of children. Due to variability in individual responses, efficacy of NEPAP should be evaluated with polysomnography. Clinical Trial Registration: www.clinicaltrials.gov, identifier: NCT01768065 Citation: Kureshi SA, Gallagher PR, McDonough JM, Cornaglia MA, Maggs J, Samuel J, Traylor J, Marcus CL. Pilot study of nasal expiratory positive airway

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

    NASA Astrophysics Data System (ADS)

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

    2010-02-01

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

  15. Continuous mucociliary transport by primary human airway epithelial cells in vitro

    PubMed Central

    Sears, Patrick R.; Yin, Wei-Ning

    2015-01-01

    Mucociliary clearance (MCC) is an important innate defense mechanism that continuously removes inhaled pathogens and particulates from the airways. Normal MCC is essential for maintaining a healthy respiratory system, and impaired MCC is a feature of many airway diseases, including both genetic (cystic fibrosis, primary ciliary dyskinesia) and acquired (chronic obstructive pulmonary disease, bronchiectasis) disorders. Research into the fundamental processes controlling MCC, therefore, has direct clinical application, but has been limited in part due to the difficulty of studying this complex multicomponent system in vitro. In this study, we have characterized a novel method that allows human airway epithelial cells to differentiate into a mucociliary epithelium that transports mucus in a continuous circular track. The mucociliary transport device allows the measurement and manipulation of all features of mucociliary transport in a controlled in vitro system. In this initial study, the effect of ciliary beat frequency and mucus concentration on the speed of mucociliary transport was investigated. PMID:25979076

  16. Long term transtracheal oxygen delivery through microcatheter in patients with hypoxaemia due to chronic obstructive airways disease.

    PubMed Central

    Banner, N R; Govan, J R

    1986-01-01

    Transtracheal administration of oxygen is a new technique for long term treatment. Twenty patients with hypoxaemia due to chronic obstructive airways disease were studied while receiving oxygen through a microcatheter inserted percutaneously into the trachea. By bypassing most of the dead space and avoiding oxygen wastage at the face this method of delivery reduced oxygen requirements by roughly half compared with delivery through nasal cannulas, thus reducing costs and facilitating portable treatment. Twelve of these patients continued to use the system for up to 13 months in preference to using nasal cannulas. Two important complications were a staphylococcal infection and a fractured catheter. Transtracheal oxygen reduced breathlessness and helped patients with routine daily activities. Transtracheal administration of oxygen is a practical method of treatment which may have an important role in rehabilitating patients with chronic lung disease. Images p112-a PMID:3089412

  17. Long-Term Effects of Continuous Positive Airway Pressure Treatment on Sexuality in Female Patients with Obstructive Sleep Apnea

    PubMed Central

    Petersen, Marian; Kristensen, Ellids; Berg, Søren; Midgren, Bengt

    2013-01-01

    Introduction Results from a previous study showed that sexuality was negatively affected in females with untreated obstructive sleep apnea (OSA). Data are sparse on the long-term effects of nocturnal continuous positive airway pressure (CPAP) treatment on sexual difficulties and sexual distress in female patients with OSA. Aim The aim of the present study was to investigate the effects after 1 year of CPAP treatment on sexual difficulties, sexual distress, and manifest sexual dysfunction in female patients with OSA. The effect of CPAP on life satisfaction was also investigated. Methods Fifty-four therapy-compliant, female patients (age 22–71) received a survey before and after 1 year of nocturnal CPAP treatment. The questions on this survey were drawn from three self-administered questionnaires: two on sexuality and one on life satisfaction. The results were compared with a population sample. The Epworth Sleepiness Scale was used for assessment of daytime sleepiness. Main Outcome Measures The Female Sexual Function Index, Female Sexual Distress Scale, Manifest Female Sexual Dysfunction, four questions from Life Satisfaction 11, and the Epworth Sleepiness Scale were all used to measure outcome. Results In total, 44 patients responded to the survey (81% response rate). The results were a significant, positive change in manifest female sexual dysfunction, but no significant changes in isolated sexual difficulties or sexual distress. Daytime sleepiness significantly decreased after 1 year. The results from the Life Satisfaction 11 questionnaire remained unchanged after 1 year. Conclusions After 1 year of CPAP treatment, female patients with OSA reported reduced manifest sexual dysfunction. However, it cannot be concluded if this result is due to CPAP treatment alone. Furthermore, reduced daytime tiredness was found in the surveyed population. CPAP treatment, per se, does not seem to affect partner relationships. Petersen M, Kristensen E, Berg S, and Midgren B. Long

  18. Autophagy plays an essential role in cigarette smoke-induced expression of MUC5AC in airway epithelium.

    PubMed

    Zhou, Jie-Sen; Zhao, Yun; Zhou, Hong-Bin; Wang, Yong; Wu, Yin-Fang; Li, Zhou-Yang; Xuan, Nan-Xia; Zhang, Chao; Hua, Wen; Ying, Song-Min; Li, Wen; Shen, Hua-Hao; Chen, Zhi-Hua

    2016-06-01

    Mucus hypersecretion is a common pathological feature of chronic airway inflammatory diseases including chronic obstructive pulmonary disease (COPD). However, the molecular basis for this condition remains incompletely understood. We have previously demonstrated a critical role of autophagy in COPD pathogenesis through mediating apoptosis of lung epithelial cells. In this study, we aimed to investigate the function of autophagy as well as its upstream and downstream signals in cigarette smoke-induced mucus production in human bronchial epithelial (HBE) cells and in mouse airways. Cigarette smoke extract (CSE), as well as the classical autophagy inducers starvation or Torin-1, significantly triggered MUC5AC expression, and inhibition of autophagy markedly attenuated CSE-induced mucus production. The CSE-induced autophagy was mediated by mitochondrial reactive oxygen species (mitoROS), which regulated mucin expression through the JNK and activator protein-1 pathway. Epidermal growth factor receptor (EGFR) was also required for CSE-induced MUC5AC in HBE cells, but it exerted inconsiderable effects on the autophagy-JNK signaling cascade. Airways of mice with dysfunctional autophagy-related genes displayed a markedly reduced number of goblet cells and attenuated levels of Muc5ac in response to cigarette smoke exposure. These results altogether suggest that mitoROS-dependent autophagy is essential for cigarette smoke-induced mucus hyperproduction in airway epithelial cells, and reemphasize autophagy inhibition as a novel therapeutic strategy for chronic airway diseases. PMID:27036871

  19. Effect of laser-assisted uvulopalatoplasty on oral airway resistance during wakefulness in obstructive sleep apnea syndrome.

    PubMed

    Lin, Ching-Chi; Lee, Kuo-Sheng; Chang, Ke-Chang; Wu, Kun-Ming; Chou, Chon-Shin

    2006-03-01

    The aim of the study was to evaluate the effects of successful laser-assisted uvulopalatoplasty (LAUP) on oral airway resistance (R(OA)) during wakefulness in patients with OSAS. Fifteen healthy subjects (group I) and 25 subjects (group II) with moderately severe or severe obstructive sleep apnea syndrome (OSAS) proven by an overnight sleep study and who desired LAUP were enrolled. All underwent an overnight sleep study, pulmonary function testing and measurement of oral airway resistance [R(OA) (including impedance (Zrs), resistance (R) and reactance (X)] measurement by Impulse Oscillometry (IOS) (MasterScreen IOS, VIASYS Healthcare GmbH, Germany) in the upright (seated) position and then in the supine position while awake. Group II subjects had these measurements twice, both before and 3 months after LAUP. Based on the assessment of their sleep study after LAUP, they were divided into two groups: responders (group IIa) and nonresponders (group IIb). Zrs was normal in the sitting position both before and after LAUP in both groups IIa and IIb and comparable to that of group I controls. There was an increase in Zrs in the supine position in both groups IIa and IIb subjects before LAUP. After LAUP, the Zrs in group IIb subjects remained elevated, while that in group IIa subjects returned to levels comparable to those in the normal controls. OSAS patients before LAUP have abnormal R(OA) in the supine position as reflected by a high Zrs. The Zrs is improved after LAUP that successfully ameliorates OSAS. PMID:16163511

  20. Numerical and experimental study of expiratory flow in the case of major upper airway obstructions with fluid structure interaction

    NASA Astrophysics Data System (ADS)

    Chouly, F.; van Hirtum, A.; Lagrée, P.-Y.; Pelorson, X.; Payan, Y.

    2008-02-01

    This study deals with the numerical prediction and experimental description of the flow-induced deformation in a rapidly convergent divergent geometry which stands for a simplified tongue, in interaction with an expiratory airflow. An original in vitro experimental model is proposed, which allows measurement of the deformation of the artificial tongue, in condition of major initial airway obstruction. The experimental model accounts for asymmetries in geometry and tissue properties which are two major physiological upper airway characteristics. The numerical method for prediction of the fluid structure interaction is described. The theory of linear elasticity in small deformations has been chosen to compute the mechanical behaviour of the tongue. The main features of the flow are taken into account using a boundary layer theory. The overall numerical method entails finite element solving of the solid problem and finite differences solving of the fluid problem. First, the numerical method predicts the deformation of the tongue with an overall error of the order of 20%, which can be seen as a preliminary successful validation of the theory and simulations. Moreover, expiratory flow limitation is predicted in this configuration. As a result, both the physical and numerical models could be useful to understand this phenomenon reported in heavy snorers and apneic patients during sleep.

  1. Airway oedema and obstruction in guinea pigs exposed to inhaled endotoxin.

    PubMed Central

    Gordon, T; Balmes, J; Fine, J; Sheppard, D

    1991-01-01

    Protein extravasation and airway conductance (SGaw) were examined in awake guinea pigs exposed to inhaled endotoxin or saline for three hours. A significant increase in protein extravasation (as estimated by the leakage of protein bound Evans blue dye) was seen in the conducting airways of endotoxin exposed animals compared with saline exposed animals. Mean dye extravasation was significantly increased by one to threefold in the mainstem and hilar bronchi of endotoxin exposed animals. These changes in extravasation were accompanied by decrements in pulmonary function and by an influx of polymorphonuclear leucocytes into the airway wall. The SGaw decreased significantly by 60-90 minutes into exposure to endotoxin and had decreased by 22% and 34% at the end of exposure in the low and high dose endotoxin groups, respectively. Similar findings were obtained in animals exposed to cotton dust. Contrary to studies suggesting that platelet activating factor (PAF) is involved in the systemic and peripheral lung effects of endotoxin, pretreatment with the PAF antagonist WEB2086 did not prevent the conducting airway injury produced by inhaled endotoxin. PMID:1911406

  2. Cut-off value of FEV1/FEV6 as a surrogate for FEV1/FVC for detecting airway obstruction in a Korean population

    PubMed Central

    Chung, Kyung Soo; Jung, Ji Ye; Park, Moo Suk; Kim, Young Sam; Kim, Se Kyu; Chang, Joon; Song, Joo Han

    2016-01-01

    Background Forced expiratory volume in 1 second (FEV1)/forced expiratory volume in 6 seconds (FEV6) has been proposed as an alternative to FEV1/forced vital capacity (FVC) for detecting airway obstruction. A fixed cut-off value for FEV1/FEV6 in a Korean population is lacking. We investigated a fixed cut-off for FEV1/FEV6 as a surrogate for FEV1/FVC for detecting airway obstruction. Materials and methods We used data obtained in the 5 years of the Fifth and Sixth Korean National Health and Nutrition Examination Survey. A total of 14,978 participants aged ≥40 years who underwent spirometry adequately were the study cohort. “Airway obstruction” was a fixed cut-off FEV1/FVC <70% according to the Global Initiative for Chronic Obstructive Lung Disease guidelines. We also used European Respiratory Society/Global Lung Initiative 2012 equations for the FEV1/FVC lower limit of normal. Results Among the 14,978 participants (43.5% male, 56.5% female; mean age: 56.9 years for men and 57.0 years for women), 14.0% had obstructive lung function according to a fixed cut-off FEV1/FVC <70%. Optimal FEV1/FEV6 cut-off for predicting FEV1/FVC <70% was 75% using receiver operating characteristic curve analyses (area under receiver operating characteristic curve =0.989, 95% confidence interval 0.987–0.990). This fixed cut-off of FEV1/FEV6 showed 93.8% sensitivity, 94.8% specificity, 74.7% positive predictive value, 98.9% negative predictive value, and 0.8 Cohen’s kappa coefficient. When compared with FEV1/FVC < lower limit of normal, FEV1/FEV6 <75% tended to over-diagnose airflow limitation (just like a fixed cut-off of FEV1/FVC <70%). When grouped according to age and FEV1 (%), FEV1/FEV6 <75% diagnosed more airway obstruction in older participants and mild–moderate stages compared with FEV1/FVC <70%. Conclusion A valid fixed cut-off for detecting airway obstruction in a Korean population is FEV1/FEV6 of 75%, but should be used with caution in older individuals and those with

  3. Oxidative stress–induced mitochondrial dysfunction drives inflammation and airway smooth muscle remodeling in patients with chronic obstructive pulmonary disease

    PubMed Central

    Wiegman, Coen H.; Michaeloudes, Charalambos; Haji, Gulammehdi; Narang, Priyanka; Clarke, Colin J.; Russell, Kirsty E.; Bao, Wuping; Pavlidis, Stelios; Barnes, Peter J.; Kanerva, Justin; Bittner, Anton; Rao, Navin; Murphy, Michael P.; Kirkham, Paul A.; Chung, Kian Fan; Adcock, Ian M.; Brightling, Christopher E.; Davies, Donna E.; Finch, Donna K.; Fisher, Andrew J.; Gaw, Alasdair; Knox, Alan J.; Mayer, Ruth J.; Polkey, Michael; Salmon, Michael; Singh, David

    2015-01-01

    Background Inflammation and oxidative stress play critical roles in patients with chronic obstructive pulmonary disease (COPD). Mitochondrial oxidative stress might be involved in driving the oxidative stress–induced pathology. Objective We sought to determine the effects of oxidative stress on mitochondrial function in the pathophysiology of airway inflammation in ozone-exposed mice and human airway smooth muscle (ASM) cells. Methods Mice were exposed to ozone, and lung inflammation, airway hyperresponsiveness (AHR), and mitochondrial function were determined. Human ASM cells were isolated from bronchial biopsy specimens from healthy subjects, smokers, and patients with COPD. Inflammation and mitochondrial function in mice and human ASM cells were measured with and without the presence of the mitochondria-targeted antioxidant MitoQ. Results Mice exposed to ozone, a source of oxidative stress, had lung inflammation and AHR associated with mitochondrial dysfunction and reflected by decreased mitochondrial membrane potential (ΔΨm), increased mitochondrial oxidative stress, and reduced mitochondrial complex I, III, and V expression. Reversal of mitochondrial dysfunction by the mitochondria-targeted antioxidant MitoQ reduced inflammation and AHR. ASM cells from patients with COPD have reduced ΔΨm, adenosine triphosphate content, complex expression, basal and maximum respiration levels, and respiratory reserve capacity compared with those from healthy control subjects, whereas mitochondrial reactive oxygen species (ROS) levels were increased. Healthy smokers were intermediate between healthy nonsmokers and patients with COPD. Hydrogen peroxide induced mitochondrial dysfunction in ASM cells from healthy subjects. MitoQ and Tiron inhibited TGF-β–induced ASM cell proliferation and CXCL8 release. Conclusions Mitochondrial dysfunction in patients with COPD is associated with excessive mitochondrial ROS levels, which contribute to enhanced inflammation and cell

  4. Obstructive sleep apnea - adults

    MedlinePlus

    Sleep apnea - obstructive - adults; Apnea - obstructive sleep apnea syndrome - adults; Sleep-disordered breathing - adults; OSA - adults ... the upper airway for obstructive sleep apnea in adults. Sleep . 2010;33:1408-1413. PMID: 21061864 www. ...

  5. Cigarette smoke exposure induces CFTR internalization and insolubility, leading to airway surface liquid dehydration

    PubMed Central

    Clunes, Lucy A.; Davies, Catrin M.; Coakley, Raymond D.; Aleksandrov, Andrei A.; Henderson, Ashley G.; Zeman, Kirby L.; Worthington, Erin N.; Gentzsch, Martina; Kreda, Silvia M.; Cholon, Deborah; Bennett, William D.; Riordan, John R.; Boucher, Richard C.; Tarran, Robert

    2012-01-01

    Cigarette smoke (CS) exposure induces mucus obstruction and the development of chronic bronchitis (CB). While many of these responses are determined genetically, little is known about the effects CS can exert on pulmonary epithelia at the protein level. We, therefore, tested the hypothesis that CS exerts direct effects on the CFTR protein, which could impair airway hydration, leading to the mucus stasis characteristic of both cystic fibrosis and CB. In vivo and in vitro studies demonstrated that CS rapidly decreased CFTR activity, leading to airway surface liquid (ASL) volume depletion (i.e., dehydration). Further studies revealed that CS induced internalization of CFTR. Surprisingly, CS-internalized CFTR did not colocalize with lysosomal proteins. Instead, the bulk of CFTR shifted to a detergent-resistant fraction within the cell and colocalized with the intermediate filament vimentin, suggesting that CS induced CFTR movement into an aggresome-like, perinuclear compartment. To test whether airway dehydration could be reversed, we used hypertonic saline (HS) as an osmolyte to rehydrate ASL. HS restored ASL height in CS-exposed, dehydrated airway cultures. Similarly, inhaled HS restored mucus transport and increased clearance in patients with CB. Thus, we propose that CS exposure rapidly impairs CFTR function by internalizing CFTR, leading to ASL dehydration, which promotes mucus stasis and a failure of mucus clearance, leaving smokers at risk for developing CB. Furthermore, our data suggest that strategies to rehydrate airway surfaces may provide a novel form of therapy for patients with CB.—Clunes, L. A., Davies, C. M., Coakley, R. D., Aleksandrov, A. A., Henderson, A. G., Zeman, K. L., Worthington, E. N., Gentzsch, M., Kreda, S. M., Cholon, D., Bennett, W. D., Riordan, J. R., Boucher, R. C., Tarran, R. Cigarette smoke exposure induces CFTR internalization and insolubility, leading to airway surface liquid dehydration. PMID:21990373

  6. Infection with Mycoplasma pneumoniae is not related to asthma control, asthma severity, and location of airway obstruction

    PubMed Central

    Ansarin, Khalil; Abedi, Siavoush; Ghotaslou, Reza; Soroush, Mohammad Hossein; Ghabili, Kamyar; Chapman, Kenneth R

    2011-01-01

    Background Mycoplasma pneumoniae is an organism that reportedly has a strong relationship to asthma. However, asthma severity and location of airway obstruction have not been compared between asthmatic patients with and without evidence for remote mycoplasma infection. Objectives The aim of this research was to study the relationship between previous M. pneumoniae infections in asthmatic patients and presence of any predilection for the involvement of central or peripheral airways, the severity of the disease, and asthma control. Methods Sixty-two patients with asthma were assessed by a validated asthma control test (ACT). All patients underwent spirometry and lung volume studies by body plethysmography. The forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), total lung capacity (TLC), residual volume (RV), and functional residual capacity (FRC) were measured. An oropharyngeal swab was obtained for polymerase chain reaction analysis to detect the mycoplasma antigen. Moreover, blood samples were obtained to measure the titration of antimycoplasma immunoglobulin M (IgM) and IgG antibodies. The asthmatic patients with a positive IgG for mycoplasma and negative PCR and negative IgM antibody were considered to have remote history of mycoplasma infection. The relationship between the asthma control using ACT score and pulmonary function variables were compared in patients with and without evidence for remote mycoplasma infection. Results The incidence of postnasal drip was higher among the patients with asthma who had no evidence for remote mycoplasma infection (61.3% vs 32%, P = 0.035). The median ACT score was 16.5 (11–22) and 20 (13.75–24) in patients with and without remote M. pneumoniae infection, respectively (P > 0.05). In addition, the medians of the predicted values of the pulmonary function test parameters (FEV1, FEV1/FVC, FRC, FRC/TLC, RV/TLC, maximal mean expiratory flow 25%–75%, forced expiratory flow [FEF] 50%, and FEF 75%) and

  7. Higher effective oronasal versus nasal continuous positive airway pressure in obstructive sleep apnea: Effect of mandibular stabilization

    PubMed Central

    Kaminska, M; Montpetit, A; Mathieu, A; Jobin, V; Morisson, F; Mayer, P

    2014-01-01

    BACKGROUND: In some individuals with obstructive sleep apnea (OSA), oronasal continuous positive airway pressure (CPAP) leads to poorer OSA correction than nasal CPAP. The authors hypothesized that this results from posterior mandibular displacement caused by the oronasal mask. OBJECTIVE: To test this hypothesis using a mandibular advancement device (MAD) for mandibular stabilization. METHODS: Subjects whose OSA was not adequately corrected by oronasal CPAP at pressures for which nasal CPAP was effective were identified. These subjects underwent polysomnography (PSG) CPAP titration with each nasal and oronasal mask consecutively, with esophageal pressure and leak monitoring, to obtain the effective pressure (Peff) of CPAP for correcting obstructive events with each mask (maximum 20 cmH2O). PSG titration was repeated using a MAD in the neutral position. Cephalometry was performed. RESULTS: Six subjects with mean (± SD) nasal Peff 10.4±3.0 cmH2O were studied. Oronasal Peff was greater than nasal Peff in all subjects, with obstructive events persisting at 20 cmH2O by oronasal mask in four cases. This was not due to excessive leak. With the MAD, oronasal Peff was reduced in three subjects, and Peff <20 cmH2O could be obtained in two of the four subjects with Peff >20 cmH2O by oronasal mask alone. Subjects’ cephalometric variables were similar to published norms. CONCLUSION: In subjects with OSA with higher oronasal than nasal Peff, this is partially explained by posterior mandibular displacement caused by the oronasal mask. Combination treatment with oronasal mask and MAD may be useful in some individuals if a nasal mask is not tolerated. PMID:24791252

  8. Effects of Nocturnal Continuous Positive Airway Pressure Therapy in Patients with Resistant Hypertension and Obstructive Sleep Apnea

    PubMed Central

    Dernaika, Tarek A.; Kinasewitz, Gary T.; Tawk, Maroun M.

    2009-01-01

    Study Objective: To examine the long-term effects of continuous positive airway pressure (CPAP) therapy on blood pressure (BP) in patients with obstructive sleep apnea and resistant hypertension. Methods: Study subjects were 98 patients with obstructive sleep apnea syndrome and hypertension who had 3 or more documented daytime BP measurements taken within 3 months of enrollment and every 3 months after CPAP initiation for 1 year. Resistant hypertension was defined as daytime BP of at least 140 mm Hg systolic or 90 mm Hg diastolic, despite the use of 3 or more antihypertensive medications. Patients in the resistant hypertension group (n = 42) were compared with subjects with controlled hypertension (n = 56). Results: Mean difference in mean arterial pressure was −5.6 (95% confidence interval [CI] −2.0 to −8.7 mm Hg; p = 0.03) in the resistant group and −0.8 mm Hg (95% CI −2.9 to 3.3 mm Hg; p = 0.53) in patients with controlled BP at the end of follow up period. CPAP permitted de-escalation of antihypertensive treatment in 71% of subjects with resistant hypertension but did not significantly alter the antihypertensive regimen in the controlled group. Multivariate regression analysis showed that baseline BP (odds ratio 5.4, 95% CI 2.3 to 8.9; p = 0.01) and diuretic therapy (odds ratio = 3.2, 95% CI 1.8 to 6.1; p = 0.02), but not apnea-hypopnea index or hours of CPAP use, were independently associated with a decrease in mean arterial pressure after 12 months of CPAP therapy. Conclusion: In this observational study, CPAP was associated with different effects on blood pressure control in hypertensive patients with sleep apnea. A beneficial response to CPAP therapy was found mainly in subjects with the most severe hypertensive disease. Citation: Dernaika TA; Kinasewitz GT; Tawk MM. Effects of nocturnal continuous positive airway pressure therapy in patients with resistant hypertension and obstructive sleep apnea. J Clin Sleep Med 2009;5(2):103–107. PMID

  9. The influence of gender and upper airway resistance on the ventilatory response to arousal in obstructive sleep apnoea in humans

    PubMed Central

    Jordan, Amy S; McEvoy, R Doug; Edwards, Jill K; Schory, Karen; Yang, Chang-Kook; Catcheside, Peter G; Fogel, Robert B; Malhotra, Atul; White, David P

    2004-01-01

    The termination of obstructive respiratory events is typically associated with arousal from sleep. The ventilatory response to arousal may be an important determinant of subsequent respiratory stability/instability and therefore may be involved in perpetuating obstructive respiratory events. In healthy subjects arousal is associated with brief hyperventilation followed by more prolonged hypoventilation on return to sleep. This study was designed to assess whether elevated sleeping upper airway resistance (RUA) alters the ventilatory response to arousal and subsequent breathing on return to sleep in patients with obstructive sleep apnoea (OSA). Inspired minute ventilation (VI), RUA and end-tidal CO2 pressure (PET,CO2) were measured in 22 patients (11 men, 11 women) with OSA (mean ±s.e.m., apnoea–hypopnoea index (AHI) 48.9 ± 5.9 events h−1) during non-rapid eye movement (NREM) sleep with low RUA (2.8 ± 0.3 cmH2O l−1 s; optimal continuous positive airway pressure (CPAP) = 11.3 ± 0.7 cmH2O) and with elevated RUA (17.6 ± 2.8 cmH2O l−1 s; sub-optimal CPAP = 8.4 ± 0.8 cmH2O). A single observer, unaware of respiratory data, identified spontaneous and tone-induced arousals of 3–15 s duration preceded and followed by stable NREM sleep. VI was compared between CPAP levels before and after spontaneous arousal in 16 subjects with tone-induced arousals in both conditions. During stable NREM sleep at sub-optimal CPAP, PET,CO2 was mildly elevated (43.5 ± 0.8 versus 42.5 ± 0.8 Torr). However, baseline VI (7.8 ± 0.3 versus 8.0 ± 0.3 l min−1) was unchanged between CPAP conditions. For the first three breaths following arousal, VI was higher for sub-optimal than optimal CPAP (first breath: 11.2 ± 0.9 versus 9.3 ± 0.6 l min−1). The magnitude of hypoventilation on return to sleep was not affected by the level of CPAP and both obstructive and central respiratory events were rare following arousal. Similar results occurred after tone-induced arousals which led to

  10. Two Cases of Cervical Hemorrhage with Upper Airway Obstruction: A Life-Threatening Condition

    PubMed Central

    Amadei, Enrico Maria; Benedettini, Laura; Piccin, Ottavio

    2014-01-01

    Several are the causes of cervical masses and among them a spontaneous hemorrhage presents a rare and life-threatening condition. Sometimes hemorrhage develops from a previous silent neck lesion as in the case of an anaplastic thyroid carcinoma associated with bleeding. We present two cases: a 70-year-old woman suffering from enlarging cervical mass causing respiratory distress because of upper airway compression due to a spontaneous rupture of the superior thyroid artery and a 74-year-old woman who drew our attention because of a progressively worsening dyspnea due to a large medial cervical mass with rapid onset. We removed it surgically, finding out an anaplastic thyroid carcinoma that is associated with internal bleeding. We discuss our management of these rare and life-threatening conditions, recalling that the patency of upper airway should always be the prerogative in every emergency. Besides, we make a review of the recent literature. PMID:24592280

  11. Acute upper airway obstruction and emergency front of neck access in an achondroplastic patient.

    PubMed

    McCaffer, Craig James; Douglas, Catriona; Wickham, Matthew H; Picozzi, Gerard L

    2015-01-01

    Dwarfism is defined as a failure to attain a height of 148 cm in adulthood. Achondroplasia is the most common form of short-limbed dwarfism. Although this condition is relatively rare, with an incidence of 0.5-1.5 per 10,000 live births, most medical professionals will come across the achondroplastic dwarf (AD) during their career. Faulty endochondral ossification produces the characteristic short stature phenotype, as well as severe craniofacial, central nervous system, spinal, respiratory and cardiac anomalies. These unusual characteristics may present airway management difficulties in elective as well as emergency situations. Within the literature there is very little information regarding the emergency insertion of a surgical airway in an adult AD. We present our experience of this situation in the form of a case report and a review of the relevant literature. PMID:25827920

  12. Chronic Bronchitis and Chronic Obstructive Pulmonary Disease

    PubMed Central

    Criner, Gerard J.

    2013-01-01

    Chronic bronchitis (CB) is a common but variable phenomenon in chronic obstructive pulmonary disease (COPD). It has numerous clinical consequences, including an accelerated decline in lung function, greater risk of the development of airflow obstruction in smokers, a predisposition to lower respiratory tract infection, higher exacerbation frequency, and worse overall mortality. CB is caused by overproduction and hypersecretion of mucus by goblet cells, which leads to worsening airflow obstruction by luminal obstruction of small airways, epithelial remodeling, and alteration of airway surface tension predisposing to collapse. Despite its clinical sequelae, little is known about the pathophysiology of CB and goblet cell hyperplasia in COPD, and treatment options are limited. In addition, it is becoming increasingly apparent that in the classic COPD spectrum, with emphysema on one end and CB on the other, most patients lie somewhere in the middle. It is known now that many patients with severe emphysema can develop CB, and small airway pathology has been linked to worse clinical outcomes, such as increased mortality and lesser improvement in lung function after lung volume reduction surgery. However, in recent years, a greater understanding of the importance of CB as a phenotype to identify patients with a beneficial response to therapy has been described. Herein we review the epidemiology of CB, the evidence behind its clinical consequences, the current understanding of the pathophysiology of goblet cell hyperplasia in COPD, and current therapies for CB. PMID:23204254

  13. Importance of back blow maneuvers in a 6 month old patient with sudden upper airway obstruction.

    PubMed

    Gencpinar, Pinar; Duman, Murat

    2015-12-01

    Foreign body aspiration in children under four years old is one of the most frequently observed reasons for accident related deaths. It is more common in this age group due to inadequate swallowing functions and exploration of objects with the mouth. The most frequently encountered foreign bodies are food and toy parts. Life threatening complete laryngeal obstruction is rarely observed. Dyspnea, hypersalivation, cough and cyanosis can be seen. The basic and life-saving treatment approach is complete removal of foreign body maneuvers in the sudden onset of total obstruction. Here we report a six-month old male, who ingested a foreign body and was treated with back blow maneuvers successfully. In this case we emphasized the importance of back blow maneuvers. PMID:27239623

  14. Vitronectin expression in the airways of subjects with asthma and chronic obstructive pulmonary disease.

    PubMed

    Salazar-Peláez, Lina M; Abraham, Thomas; Herrera, Ana M; Correa, Mario A; Ortega, Jorge E; Paré, Peter D; Seow, Chun Y

    2015-01-01

    Vitronectin, a multifunctional glycoprotein, is involved in coagulation, inhibition of the formation of the membrane attack complex (MAC), cell adhesion and migration, wound healing, and tissue remodeling. The primary cellular source of vitronectin is hepatocytes; it is not known whether resident cells of airways produce vitronectin, even though the glycoprotein has been found in exhaled breath condensate and bronchoalveolar lavage from healthy subjects and patients with interstitial lung disease. It is also not known whether vitronectin expression is altered in subjects with asthma and COPD. In this study, bronchial tissue from 7 asthmatic, 10 COPD and 14 control subjects was obtained at autopsy and analyzed by immunohistochemistry to determine the percent area of submucosal glands occupied by vitronectin. In a separate set of experiments, quantitative colocalization analysis was performed on tracheobronchial tissue sections obtained from donor lungs (6 asthmatics, 4 COPD and 7 controls). Vitronectin RNA and protein expressions in bronchial surface epithelium were examined in 12 subjects who undertook diagnostic bronchoscopy. Vitronectin was found in the tracheobronchial epithelium from asthmatic, COPD, and control subjects, although its expression was significantly lower in the asthmatic group. Colocalization analysis of 3D confocal images indicates that vitronectin is expressed in the glandular serous epithelial cells and in respiratory surface epithelial cells other than goblet cells. Expression of the 65-kDa vitronectin isoform was lower in bronchial surface epithelium from the diseased subjects. The cause for the decreased vitronectin expression in asthma is not clear, however, the reduced concentration of vitronectin in the epithelial/submucosal layer of airways may be linked to airway remodeling. PMID:25768308

  15. Vitronectin Expression in the Airways of Subjects with Asthma and Chronic Obstructive Pulmonary Disease

    PubMed Central

    Salazar-Peláez, Lina M.; Abraham, Thomas; Herrera, Ana M.; Correa, Mario A.; Ortega, Jorge E.; Paré, Peter D.; Seow, Chun Y.

    2015-01-01

    Vitronectin, a multifunctional glycoprotein, is involved in coagulation, inhibition of the formation of the membrane attack complex (MAC), cell adhesion and migration, wound healing, and tissue remodeling. The primary cellular source of vitronectin is hepatocytes; it is not known whether resident cells of airways produce vitronectin, even though the glycoprotein has been found in exhaled breath condensate and bronchoalveolar lavage from healthy subjects and patients with interstitial lung disease. It is also not known whether vitronectin expression is altered in subjects with asthma and COPD. In this study, bronchial tissue from 7 asthmatic, 10 COPD and 14 control subjects was obtained at autopsy and analyzed by immunohistochemistry to determine the percent area of submucosal glands occupied by vitronectin. In a separate set of experiments, quantitative colocalization analysis was performed on tracheobronchial tissue sections obtained from donor lungs (6 asthmatics, 4 COPD and 7 controls). Vitronectin RNA and protein expressions in bronchial surface epithelium were examined in 12 subjects who undertook diagnostic bronchoscopy. Vitronectin was found in the tracheobronchial epithelium from asthmatic, COPD, and control subjects, although its expression was significantly lower in the asthmatic group. Colocalization analysis of 3D confocal images indicates that vitronectin is expressed in the glandular serous epithelial cells and in respiratory surface epithelial cells other than goblet cells. Expression of the 65-kDa vitronectin isoform was lower in bronchial surface epithelium from the diseased subjects. The cause for the decreased vitronectin expression in asthma is not clear, however, the reduced concentration of vitronectin in the epithelial/submucosal layer of airways may be linked to airway remodeling. PMID:25768308

  16. Comparison of genomic and proteomic data in recurrent airway obstruction affected horses using ingenuity pathway analysis®

    PubMed Central

    2011-01-01

    Background Recurrent airway obstruction (RAO) is a severe chronic respiratory disease affecting horses worldwide, though mostly in the Northern hemisphere. Environmental as well as genetic factors strongly influence the course and prognosis of the disease. Research has been focused on characterization of immunologic factors contributing to inflammatory responses, on genetic linkage analysis, and, more recently, on proteomic analysis of airway secretions from affected horses. The goal of this study was to investigate the interactions between eight candidate genes previously identified in a genetic linkage study and proteins expressed in bronchoalveolar lavage fluid (BALF) collected from healthy and RAO-affected horses. The analysis was carried out with Ingenuity Pathway Analysis® bioinformatics software. Results The gene with the greatest number of indirect interactions with the set of proteins identified is Interleukin 4 Receptor (IL-4R), whose protein has also been detected in BALF. Interleukin 21 receptor and chemokine (C-C motif) ligand 24 also showed a large number of interactions with the group of detected proteins. Protein products of other genes like that of SOCS5, revealed direct interactions with the IL-4R protein. The interacting proteins NOD2, RPS6KA5 and FOXP3 found in several pathways are reported regulators of the NFκB pathway. Conclusions The pathways generated with IL-4R highlight possible important intracellular signaling cascades implicating, for instance, NFκB. Furthermore, the proposed interaction between SOCS5 and IL-4R could explain how different genes can lead to identical clinical RAO phenotypes, as observed in two Swiss Warmblood half sibling families because these proteins interact upstream of an important cascade where they may act as a functional unit. PMID:21843342

  17. Aerosol Medications for Treatment of Mucus Clearance Disorders.

    PubMed

    Rubin, Bruce K

    2015-06-01

    Airway mucus hypersecretion and secretion retention can result from inflammation, irritation, stimulation, or mucus-producing tumors. Secretion clearance can be furthered hampered by ciliary dysfunction and by weakness or restrictive lung disease, leading to an ineffective cough. There are a number of different mucoactive medications that have been used to reduce hypersecretion, make secretions easier to transport, or increase the efficiency of cough or mucus clearance. In this paper, I review the pathophysiology of secretory hyper-responsiveness and mucus hypersecretion and discuss the different aerosol medications that can be used to augment secretion clearance. PMID:26070577

  18. Effects of inhaled budesonide on spirometric values, reversibility, airway responsiveness, and cough threshold in smokers with chronic obstructive lung disease.

    PubMed Central

    Auffarth, B; Postma, D S; de Monchy, J G; van der Mark, T W; Boorsma, M; Koëter, G H

    1991-01-01

    Inhaled corticosteroids are known to reduce respiratory symptoms and airway responsiveness in allergic patients with asthma. The aim of the present randomised, double blind study was to assess the effect of eight weeks' treatment with inhaled budesonide in non-allergic smokers with chronic obstructive lung disease. Twenty four subjects (23 male) entered the study. Their ages ranged from 40 to 70 (mean 57) years, with a mean of 35 (range 9-80) pack years of smoking; the mean FEV1 was 53% (range 32-74%) predicted and geometric mean PC20 (histamine concentration causing a 20% fall in FEV1) 0.96 (range 0.07-7.82) mg/ml. After a two week washout, single blind, placebo period, 12 patients were allocated to treatment with budesonide 1600 microgram/day and 12 to placebo for eight weeks. The only additional drug to be taken was ipratropium bromide "if needed." Twenty one patients completed the study, 10 in the budesonide group and 11 in the placebo group. The standard deviation of the difference between duplicate measurements of PC20 histamine and citric acid cough threshold made two weeks apart was below one doubling dose step. There was a significant reduction in dyspnoea in the budesonide group, but otherwise no change in symptom scores or use of ipratropium bromide over the eight weeks of treatment within or between the two groups. No significant differences in spirometric values, peak expiratory flow, PC20 histamine, or citric acid cough threshold were found between the groups. Although differences were not significant, some of the changes showed a trend in favour of budesonide. Whether a longer observation period would show a significant influence of inhaled corticosteroids in patients with chronic obstructive lung disease remains to be determined. Images PMID:2068695

  19. Evaluation of C-reactive protein, Haptoglobin and cardiac troponin 1 levels in brachycephalic dogs with upper airway obstructive syndrome

    PubMed Central

    2012-01-01

    Background Brachycephalic dogs have unique upper respiratory anatomy with abnormal breathing patterns similar to those in humans with obstructive sleep apnea syndrome (OSAS). The objective of this study was to evaluate the correlation between anatomical components, clinical signs and several biomarkers, used to determine systemic inflammation and myocardial damage (C-reactive protein, CRP; Haptoglobin, Hp; cardiac troponin I, cTnI), in dogs with brachycephalic upper airway obstructive syndrome (BAOS). Results Fifty brachycephalic dogs were included in the study and the following information was studied: signalment, clinical signs, thoracic radiographs, blood work, ECG, components of BAOS, and CRP, Hp and cTnI levels. A high proportion of dogs with BAOS (88%) had gastrointestinal signs. The prevalence of anatomic components of BAOS was: elongated soft palate (100%), stenotic nares (96%), everted laryngeal saccules (32%) and tracheal hypoplasia (29.1%). Increased serum levels of biomarkers were found in a variable proportion of dogs: 14% (7/50) had values of CRP > 20 mg/L, 22.9% (11/48) had values of Hp > 3 g/L and 47.8% (22/46) had levels of cTnI > 0.05 ng/dl. Dogs with everted laryngeal saccules had more severe respiratory signs (p<0.02) and higher values of CRP (p<0.044). No other statistical association between biomarkers levels and severity of clinical signs was found. Conclusions According to the low percentage of patients with elevated levels of CRP and Hp, BAOS does not seem to cause an evident systemic inflammatory status. Some degree of myocardial damage may occur in dogs with BAOS that can be detected by cTnI concentration. PMID:22937913

  20. The influence of multilevel upper airway surgery on CPAP tolerance in non-responders to obstructive sleep apnea surgery.

    PubMed

    Azbay, Sule; Bostanci, Asli; Aysun, Yasin; Turhan, Murat

    2016-09-01

    The aim of this study was to evaluate the influence of multilevel upper airway surgery on subsequent continuous positive airway pressure (CPAP) use and tolerance in patients with moderate to severe obstructive sleep apnea (OSA). The study cohort enrolled 67 consecutive patients, who underwent septoplasty plus modified uvulopharyngopalatoplasty (mUPPP) with or without modified tongue base suspension (mTBS) due to CPAP intolerance, and who had residual OSA requiring CPAP therapy [non-responders to surgery, apnea-hypopnea index (AHI) >15 events/h] that had been confirmed by control polysomnography at the sixth month postoperatively. A questionnaire including questions on postoperative CPAP use, problems faced during CPAP use after the surgery, change in OSA symptoms, and satisfaction with the surgery was designed, and filled through interviews. Seventeen (25.4 %) patients had septoplasty plus mUPPP and 50 (74.6 %) had septoplasty plus mUPPP combined with mTBS. Postoperatively, mean AHI (45.00 ± 19.76 vs. 36.60 ± 18.34), Epworth sleepiness scale (ESS) score (18.00 ± 4.45 vs. 13.00 ± 4.72), oxygen desaturation index (ODI) (48.98 ± 16.73 vs. 37.81 ± 17.03), and optimal CPAP level (11.80 ± 1.40 vs. 8.96 ± 1.20) were decreased (p < 0.001 for all parameters). Fifty-nine percent of patients reported that they fairly satisfied with the surgery and 49.2 % reported that their symptoms were completely resolved. While none of the cases could tolerate CPAP before surgery, almost half (47.8 %) of the cases used CPAP without problems postoperatively. Postoperative CPAP users had significantly higher postoperative AHI (p = 0.001), supine AHI (p = 0.009), ESS (p = 0.019), and ODI (p = 0.014), and significantly lower postoperative minimum O2 saturation (p = 0.001) compared with non-users. Multilevel upper airway surgery with less invasive techniques may improve CPAP tolerance in well-selected patients. PMID:26714802

  1. The relationship between the duration of obstructive respiratory events and outcomes of multilevel upper airway surgery in patients with obstructive sleep apnea.

    PubMed

    Bostanci, Asli; Bozkurt, Selen; Turhan, Murat

    2016-09-01

    We aimed to examine whether the duration of respiratory events and related oximetric values are associated with outcomes of multilevel upper airway surgery in patients with moderate-severe obstructive sleep apnea (OSA). The records of patients with a preoperative apnea-hypopnea index (AHI) >15 events/h, who underwent uvulopharyngopalatoplasty plus tongue base suspension with or without septoplasty between 2012 and 2014, were reviewed retrospectively. If the postoperative 6th month AHI was <20 events/h with at least a 50 % reduction from preoperative rates, the outcome of surgery was regarded as successful, otherwise, as failure. To calculate factors predictive of surgical outcomes, a receiver operating characteristic (ROC) analysis was performed. Logistic regression analyses were utilized to obtain the Odds ratio (OR) and 95 % confidential interval (CI). In total, 82 patients were enrolled in the study. Sixty-one patients (74.4 %) met the success criteria. The mean obstructive apnea duration (OAD) was the sole variable with a significant and satisfactory area under the curve (AUC) value [AUC (95 % CI) = 0.719 (0.597-0.842), p = 0.003]. The cutoff value was found to be 26.75 s with 71.4 % sensitivity, 72.1 % specificity, 88.0 % positive predictive value, and 46.9 % negative predictive value. Univariate analysis revealed an association between surgical failure and mean OAD > 26.75 s, total apnea duration, lowest SaO2, mean SaO2, mean O2 desaturation, and oxygen desaturation index, although only mean OAD > 26.75 s remained to be an independent predictor for unfavorable outcome after adjustment for other confounders in multivariate analysis [OR (95 % CI) = 3.92 (1.08-14.17), p = 0.041]. The current study suggests that OSA patients having longer OAD are in the risk of having surgical failure. PMID:26370234

  2. Impact of nasal airway obstruction on dentofacial development and sleep disturbances in children: preliminary notes.

    PubMed

    Defabjanis, Patrizia

    2003-01-01

    Respiratory disorders in the upper respiratory tract during sleep are most often part of a continuous pathological process of long standing. Schematically, three clinical syndromes with increasing severity are described: breathing with the mouth open, snoring and sleep apneal hypopnea syndrome. Obstructive sleep apnea syndrome (OSAS) is a subtle, but severe sleep disorder of early childhood. It is often difficult to detect and may have long-term consequences, including failure to thrive, behavioral disturbances, developmental delay, and cor pulmonale. These conditions always include a functional maxillofacial perturbation, which may be associated with a constitutional or acquired morphological disorder. Pediatric dentists must be aware of the problems connected with mouth breathing and OSAS (obstructive sleep apnea syndrome) in children as any delay in diagnosis and treatment may cause prolonged morbidity. They also have a role in the diagnosis and co-management of these patients because the signs and symptoms may be recognizable in the dental practice. Besides the medical approach itself, the treatment sometimes is surgical, always orthopedic: the earlier it is initiated, the more effective, simple and unrestraining it is. The aim of this work is to focus attention on the early diagnosis and prevention of these pathologies. Diagnostic guidelines will be illustrated. PMID:12597677

  3. The Impact of Obstructive Sleep Apnoea and Nasal Continuous Positive Airway Pressure on Circulating Ischaemia-Modified Albumin Concentrations

    PubMed Central

    Uygur, Firat; Tanriverdi, Hakan; Can, Murat; Ornek, Tacettin; Erboy, Fatma; Altinsoy, Bulent; Atalay, Figen; Damar, Murat; Kokturk, Furuzan; Tor, Meltem

    2016-01-01

    The aim of the present study was to evaluate the impact of obstructive sleep apnoea syndrome (OSAS) and the effects of nasal continuous positive airway pressure (CPAP) on circulating ischaemia-modified albumin (IMA) concentrations. The study included 97 newly diagnosed OSAS patients and 30 nonapnoeic controls. Blood samples were obtained in the morning after polysomnography. After 3 months of CPAP treatment, 31 patients with moderate-severe OSAS were reassessed for serum IMA concentrations. Significantly higher serum IMA concentrations were measured in the OSAS group than in the control group [0.518 ± 0.091 absorbance units (ABSU), 0.415 ± 0.068 ABSU, P < 0.001]. Serum IMA concentrations correlated significantly with the apnoea-hypopnoea index, mean SaO2, desaturation index, and C-reactive protein concentrations. Multiple logistic regression analyses showed that OSAS increased the serum IMA concentration independent of age, sex, body mass index, smoking habit, and cardiovascular disease. After 3 months of treatment with CPAP, OSAS patients had significantly lower serum IMA concentrations (0.555 ± 0.062 ABSU to 0.431 ± 0.063 ABSU, P < 0.001). The results showed that OSAS is associated with elevated concentrations of IMA, which can be reversed by effective CPAP treatment. PMID:26903714

  4. Continuous positive airway pressure therapy is associated with improvement in overactive bladder symptoms in women with obstructive sleep apnea syndrome

    PubMed Central

    Ipekci, Tumay; Cetintas, Gulgun; Celik, Orcun; Sarac, Sema; Tunckiran, Ahmet; Ilbey, Yusuf Ozlem

    2016-01-01

    Introduction To evaluate the impact of continuous positive airway pressure (CPAP) therapy on overactive bladder (OAB) symptoms in women with obstructive sleep apnea syndrome (OSAS). Material and methods One-hundred and fifty women underwent an overnight polysomnography study between May 2014 and September 2014. Their voiding symptoms were evaluated using the OAB symptom score (OABSS) and International Consultation on Incontinence Questionnaire Short-Form at OSAS diagnosis and approximately 3-months after CPAP therapy. OSAS severity was assessed according to the apnea-hypopnea-index. Results We evaluated 140 women and 111 of them (79.3%) reported symptoms consistent with OAB. There were no statistically significant differences between OSAS severity with a prevalence of OAB (p = 0.92). The prevalence of urinary incontinence (UI) was 35.7% (n = 50) and 39.6% (n = 44) in all patients and patients with OAB, respectively. There were no statistically significant differences between UI with OAB (p = 0.58). Baseline OABSS is comparable between OSAS severity (p = 0.143). After 3-months CPAP therapy, OABSS and ICIQ-SF sum scores were significantly decreased in patients with severe and moderate OSAS (p <0.01), however, change of OABSS sum score was insignificant in patients with mild OSAS (p = 0.44). Conclusions CPAP therapy improves the OAB, OABSS and ICIQ-SF scores in women with severe and moderate OSAS. OSAS-induced OAB may be alleviated following CPAP therapy. PMID:27123331

  5. Sodium hypochlorite accident resulting in life-threatening airway obstruction during root canal treatment: a case report

    PubMed Central

    Al-Sebaei, Maisa O; Halabi, Omar A; El-Hakim, Ibrahim E

    2015-01-01

    Aim This case report describes a serious and life-threatening complication of the use of sodium hypochlorite as an irrigation solution in root canal therapy. Summary This case report describes a hypochlorite accident that occurred in a healthy 42-year-old female who was undergoing routine root canal therapy for the lower right central incisor (tooth #41). After approximately 1 hour of irrigation with 3% sodium hypochlorite (for a total of 12 cc), the patient complained of severe pain and burning in the lip. The swelling progressed over the next 8 hours to involve the sublingual and submental fascial spaces with elevation of the tongue and resultant upper airway obstruction. The patient was intubated and remained on mechanical ventilation for 3 days. She recovered without any skin necrosis or nerve deficits. Key learning points This case report highlights the importance of carefully performing root canal irrigation with sodium hypochlorite to avoid complications. Careful injection without pressure, the use of proper rubber dam isolation, and the use of the endodontic needle are necessary to avoid this type of complication. Although it is a safe root canal irrigation solution, its use may lead to life-threatening complications. Early recognition and management of the untoward effects of sodium hypochlorite are vital for the patient’s safety. PMID:25767406

  6. A Comparison of Personality Characteristics and Psychiatric Symptomatology between Upper Airway Resistance Syndrome and Obstructive Sleep Apnea Syndrome

    PubMed Central

    So, Soo-Jung; Kang, Seung-Gul; Cho, Chul-Hyun; Yoon, Ho-Kyoung; Kim, Leen

    2015-01-01

    Objective To investigate the personality characteristics of patients with upper airway resistance syndrome (UARS) and those of patients with obstructive sleep apnea syndrome (OSAS). Methods Eighty-eight patients with UARS and 365 patients with OSAS participated. All patients had a diagnostic full-night attended polysomnography (PSG) and completed the Athens Insomnia Scale (AIS), Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), Symptom Checklist-90-Revision (SCL-90-R) and Eysenck Personality Questionnaire (EPQ). Results The UARS group scored significantly higher than the OSAS group on the ESS, AIS, and PSQI (p<0.001). The scores of all SCL-90-R subscales in the UARS group were significantly higher than those in the OSA group (all p<0.001, except for somatization, p=0.016). Patients with UARS scored lower on EPQ-E (extroversion/introversion) (p=0.006) and EPQ-L (lie) (p<0.001) than those with OSA. UARS patients also showed higher scores on EPQ-P (psychoticism) (p=0.002) and EPQ-N (neuroticism) (p<0.001) than OSAS patients. Conclusion Our results suggest that patients with UARS have worse subjective sleep quality than OSAS patients in spite of their better PSG findings. UARS patients tend to have more neurotic and sensitive personalities than patients with OSAS, which may be a cause of the clinical features of UARS. PMID:25866518

  7. Effects of nasal continuous positive airway pressure and oxygen supplementation on norepinephrine kinetics and cardiovascular responses in obstructive sleep apnea.

    PubMed

    Mills, Paul J; Kennedy, Brian P; Loredo, Jose S; Dimsdale, Joel E; Ziegler, Michael G

    2006-01-01

    Obstructive sleep apnea (OSA) is characterized by noradrenergic activation. Nasal continuous positive airway pressure (CPAP) is the treatment of choice and has been shown to effectively reduce elevated norepinephrine (NE) levels. This study examined whether the reduction in NE after CPAP is due to an increase in NE clearance and/or a decrease of NE release rate. Fifty CPAP-naive OSA patients with an apnea-hypopnea index >15 were studied. NE clearance and release rates, circulating NE levels, urinary NE excretion, and blood pressure and heart rate were determined before and after 14 days of CPAP, placebo CPAP (CPAP administered at ineffective pressure), or oxygen supplementation. CPAP led to a significant increase in NE clearance (P < or = 0.01), as well as decreases in plasma NE levels (P < or = 0.018) and daytime (P < 0.001) and nighttime (P < 0.05) NE excretion. NE release rate was unchanged with treatment. Systolic (P < or = 0.013) and diastolic (P < or = 0.026) blood pressure and heart rate (P < or = 0.014) were decreased in response to CPAP but not in response to oxygen or placebo CPAP treatment. Posttreatment systolic blood pressure was best predicted by pretreatment systolic blood pressure and posttreatment NE clearance and release rate (P < 0.01). The findings indicate that one of the mechanisms through which CPAP reduces NE levels is through an increase in the clearance of NE from the circulation. PMID:16357087

  8. Effects of 12 Months Continuous Positive Airway Pressure on Sympathetic Activity Related Brainstem Function and Structure in Obstructive Sleep Apnea.

    PubMed

    Henderson, Luke A; Fatouleh, Rania H; Lundblad, Linda C; McKenzie, David K; Macefield, Vaughan G

    2016-01-01

    Muscle sympathetic nerve activity (MSNA) is greatly elevated in patients with obstructive sleep apnea (OSA) during normoxic daytime wakefulness. Increased MSNA is a precursor to hypertension and elevated cardiovascular morbidity and mortality. However, the mechanisms underlying the high MSNA in OSA are not well understood. In this study we used concurrent microneurography and magnetic resonance imaging to explore MSNA-related brainstem activity changes and anatomical changes in 15 control and 15 OSA subjects before and after 6 and 12 months of continuous positive airway pressure (CPAP) treatment. We found that following 6 and 12 months of CPAP treatment, resting MSNA levels were significantly reduced in individuals with OSA. Furthermore, this MSNA reduction was associated with restoration of MSNA-related brainstem activity and structural changes in the medullary raphe, rostral ventrolateral medulla, dorsolateral pons, and ventral midbrain. This restoration occurred after 6 months of CPAP treatment and was maintained following 12 months CPAP. These findings show that continual CPAP treatment is an effective long-term treatment for elevated MSNA likely due to its effects on restoring brainstem structure and function. PMID:27013952

  9. Effects of 12 Months Continuous Positive Airway Pressure on Sympathetic Activity Related Brainstem Function and Structure in Obstructive Sleep Apnea

    PubMed Central

    Henderson, Luke A.; Fatouleh, Rania H.; Lundblad, Linda C.; McKenzie, David K.; Macefield, Vaughan G.

    2016-01-01

    Muscle sympathetic nerve activity (MSNA) is greatly elevated in patients with obstructive sleep apnea (OSA) during normoxic daytime wakefulness. Increased MSNA is a precursor to hypertension and elevated cardiovascular morbidity and mortality. However, the mechanisms underlying the high MSNA in OSA are not well understood. In this study we used concurrent microneurography and magnetic resonance imaging to explore MSNA-related brainstem activity changes and anatomical changes in 15 control and 15 OSA subjects before and after 6 and 12 months of continuous positive airway pressure (CPAP) treatment. We found that following 6 and 12 months of CPAP treatment, resting MSNA levels were significantly reduced in individuals with OSA. Furthermore, this MSNA reduction was associated with restoration of MSNA-related brainstem activity and structural changes in the medullary raphe, rostral ventrolateral medulla, dorsolateral pons, and ventral midbrain. This restoration occurred after 6 months of CPAP treatment and was maintained following 12 months CPAP. These findings show that continual CPAP treatment is an effective long-term treatment for elevated MSNA likely due to its effects on restoring brainstem structure and function. PMID:27013952

  10. High altitude, continuous positive airway pressure, and obstructive sleep apnea: subjective observations and objective data.

    PubMed

    Ginosar, Yehuda; Malhotra, Atul; Schwartz, Eli

    2013-06-01

    We report observations made by one of the authors who ascended to the Thorang La pass (5416 m) in the Nepal Himalaya in October 2010, despite moderate-severe obstructive sleep apnea. We report the first recorded use of nasal CPAP to treat high altitude pulmonary edema (progressively severe dyspnea at rest and severe orthopnea, with tachycardia and tachypnea) that occurred at 4400 meters, when snow and darkness made safe evacuation difficult. We also present objective longitudinal data of the effects of altitude on auto-adjusting CPAP delivered via a portable nasal CPAP device, and on the apnea hypopnea index measured during sleep while using the device. OSA may be a risk factor for the development of high altitude pulmonary edema and we suggest that a nasal CPAP device located in high altitude trekking stations may provide an additional or alternative treatment option for managing high altitude pulmonary edema until evacuation is possible. PMID:23795742

  11. Airway Remodeling in Chronic Obstructive Pulmonary Disease and Asthma: the Role of Matrix Metalloproteinase-9.

    PubMed

    Grzela, Katarzyna; Litwiniuk, Malgorzata; Zagorska, Wioletta; Grzela, Tomasz

    2016-02-01

    Chronic obstructive pulmonary disease (COPD) and asthma are both associated with airflow restriction and progressive remodeling, which affect the respiratory tract. Among various biological factors involved in the pathomechanisms of both diseases, proteolytic enzymes--matrix metalloproteinases (MMPs)--play an important role, especially MMP-9. In this review, the authors discuss the current topics of research concerning the possible role of MMP-9 in both mentioned diseases. They include the analysis of protein levels, nucleotide polymorphisms of MMP-9 gene and their possible correlation with asthma and COPD. Finally, the authors refer to the studies on MMP-9 inhibition as a new perspective for increasing the effectiveness of treatment in asthma and COPD. PMID:26123447

  12. Ambroxol inhalation ameliorates LPS-induced airway inflammation and mucus secretion through the extracellular signal-regulated kinase 1/2 signaling pathway.

    PubMed

    Zhang, Shui-Juan; Jiang, Juan-Xia; Ren, Qian-Qian; Jia, Yong-Liang; Shen, Jian; Shen, Hui-Juan; Lin, Xi-Xi; Lu, Hong; Xie, Qiang-Min

    2016-03-15

    Ambroxol, a metabolite of bromhexine, is shown to exert several pharmacological activities, including secretolytic, anti-inflammatory and antioxidant actions. Oral and intravenous administration of ambroxol is useful for the airway inflammatory diseases. However, little is known about its potential in inhalation therapy for lipopolysaccharide (LPS)-induced mucous hypersecretion and inflammatory response. In the present study, we compared the pharmacological effects of ambroxol by inhalation with intravenous administration and preliminarily explored its mechanism of action. Our results demonstrated that ambroxol administered by inhalation inhibited MUC5AC expression, reduced glycosaminoglycan levels, enhanced the function of mucociliary clearance and promoted sputum excretion, suggesting that ambroxol increases expectoration of sputum by reducing its viscosity. Moreover, ambroxol significantly alleviated LPS-induced the influx of inflammatory cells and the extracellular signal-regulated kinase 1/2 (Erk 1/2) expression in lung tissues, and inhibited increases in the mRNA expression of the pro-inflammatory cytokines tumor necrosis factor (TNF)-α, CCL-2 (monocyte chemotactic protein-1), KC (keratinocyte cell protein) and interleukin (IL)-1β in lung tissues. The secretolytic and anti-inflammatory effects of inhaled ambroxol at a dose of 7.5mg/ml was comparable to that of ambroxol at 20mg/ml i.v. and dexamethasone at 0.5mg/kg i.p. In addition, we found that ambroxol dose-dependently inhibited LPS-induced increases in the mRNA expression of MUC5AC, TNF-α, and IL-1β in human bronchial epithelial cell (NCI-H292) by inhibiting the Erk signaling pathway. These results demonstrate the beneficial effects of ambroxol in inhalation therapy for the airway inflammatory diseases. PMID:26872986

  13. MR Image Analytics to Characterize the Upper Airway Structure in Obese Children with Obstructive Sleep Apnea Syndrome

    PubMed Central

    Tong, Yubing; Udupa, Jayaram K.; Sin, Sanghun; Liu, Zhengbing; Wileyto, E. Paul; Torigian, Drew A.; Arens, Raanan

    2016-01-01

    Purpose Quantitative image analysis in previous research in obstructive sleep apnea syndrome (OSAS) has focused on the upper airway or several objects in its immediate vicinity and measures of object size. In this paper, we take a more general approach of considering all major objects in the upper airway region and measures pertaining to their individual morphological properties, their tissue characteristics revealed by image intensities, and the 3D architecture of the object assembly. We propose a novel methodology to select a small set of salient features from this large collection of measures and demonstrate the ability of these features to discriminate with very high prediction accuracy between obese OSAS and obese non-OSAS groups. Materials and Methods Thirty children were involved in this study with 15 in the obese OSAS group with an apnea-hypopnea index (AHI) = 14.4 ± 10.7) and 15 in the obese non-OSAS group with an AHI = 1.0 ± 1.0 (p<0.001). Subjects were between 8–17 years and underwent T1- and T2-weighted magnetic resonance imaging (MRI) of the upper airway during wakefulness. Fourteen objects in the vicinity of the upper airways were segmented in these images and a total of 159 measurements were derived from each subject image which included object size, surface area, volume, sphericity, standardized T2-weighted image intensity value, and inter-object distances. A small set of discriminating features was identified from this set in several steps. First, a subset of measures that have a low level of correlation among the measures was determined. A heat map visualization technique that allows grouping of parameters based on correlations among them was used for this purpose. Then, through T-tests, another subset of measures which are capable of separating the two groups was identified. The intersection of these subsets yielded the final feature set. The accuracy of these features to perform classification of unseen images into the two patient groups was

  14. Mathematical Equations to Predict Positive Airway Pressures for Obstructive Sleep Apnea: A Systematic Review

    PubMed Central

    Camacho, Macario; Riaz, Muhammad; Tahoori, Armin; Certal, Victor; Kushida, Clete A.

    2015-01-01

    Objective. To systematically review the international literature for mathematical equations used to predict effective pressures for positive airway pressure (PAP) devices. Methods. Google Scholar, PubMed, Scopus, Embase, Web of Science, CINAHL, and The Cochrane Library were searched through June 27, 2015. The PRISMA statement was followed. There was no language limitation. Results. 709 articles were screened, fifty were downloaded, and twenty-six studies presented equations that met the inclusion and exclusion criteria. In total, there were 4,436 patients in the development phases and 3,489 patients in the validation phases. Studies performed multiple linear regressions analyses as part of the equation(s) development and included the following variables: physical characteristics, polysomnography data, behavioral characteristics, and miscellaneous characteristics, which were all predictive to a variable extent. Of the published variables, body mass index (BMI) and mean oxygen saturation are the most heavily weighted, while BMI (eighteen studies), apnea-hypopnea index (seventeen studies), and neck circumference (eleven studies) were the variables most frequently used in the mathematical equations. Ten studies were from Asian countries and sixteen were from non-Asian countries. Conclusion. This systematic review identified twenty-six unique studies reporting mathematical equations which are summarized. Overall, BMI and mean oxygen saturation are the most heavily weighted. PMID:26294977

  15. Differential diagnosis and management of airway obstruction in Riedel's thyroiditis: a case report.

    PubMed

    Sato, Katsuro; Hanazawa, Hideyuki; Watanabe, Jun; Takahashi, Sugata

    2005-12-01

    A case of Riedel's thyroiditis, which required differential diagnosis from malignant tumor of the thyroid gland, and the strategy of surgical treatment is reported. Differential diagnosis prior to the treatment was difficult, but the diagnosis was decided by the histopathological findings of an open biopsy specimen obtained simultaneously in an emergent tracheostomy required for progressive airway stenosis. First-choice treatment for Riedel's thyroiditis has been reported to be steroid administration, however, this treatment was difficult for the present case due to continuous steroid treatment for complicated neuro-Behçet's disease. Therefore, vaporization of the lesion using KTP-LASER and T-tube placement was chosen for the surgical treatment strategy of this patient. After 1 year of follow-up since the operation, the T-tube was removed and the tracheostoma was closed, and the patient has remained symptom free for 412 years. Careful long-term follow-up is still needed for this patient to prevent recurrence of the disease, subsequent complications of autoimmune diseases, and thyroid malignancies. PMID:16029941

  16. Evaluation of an oral appliance in patients with mild to moderate obstructive sleep apnea syndrome intolerant to continuous positive airway pressure use: Preliminary results.

    PubMed

    Cantore, S; Ballini, A; Farronato, D; Malcangi, G; Dipalma, G; Assandri, F; Garagiola, U; Inchingolo, F; De Vito, D; Cirulli, N

    2016-06-01

    Obstructive sleep apnea syndrome (OSAS) is a phenomenon of repeated, episodic reduction, or cessation of airflow (hypopnea/apnea) as a result of upper airways obstruction. First-line treatment in younger children is adenotonsillectomy, although other available treatment options in middle-aged adults include continuous positive airways pressure (CPAP) and airway adjuncts. Oral appliances (OA) are a viable treatment alternative in patients with OSAS.The objective of this study was to assess, in a 1-year follow-up study, an OA in OSAS patients. The participants were subjected to polysomnographic examination with a validated device (MicroMESAM). Eight participants were fitted with a Thornton Adjustable Positioner (TAP). The participants were asked to wear the test appliance for 7 nights, and in case of compliance, for 6 months. The selected patients record their usage of the appliance and any adverse effects in a treatment journal. The research focused on the following outcomes: sleep apnea (i.e. reduction in the apnea/hypopnea index) and the effect of oral appliances on daytime function.In conclusion, the results suggest that OA have a definite role in the treatment of snoring and sleep apnea. PMID:26684627

  17. Lung function and airway obstruction: associations with circulating markers of cardiac function and incident heart failure in older men—the British Regional Heart Study

    PubMed Central

    Wannamethee, S Goya; Shaper, A Gerald; Papacosta, Olia; Lennon, Lucy; Welsh, Paul; Whincup, Peter H

    2016-01-01

    Aims The association between lung function and cardiac markers and heart failure (HF) has been little studied in the general older population. We have examined the association between lung function and airway obstruction with cardiac markers N-terminal pro-brain natriuretic peptide (NT-proBNP) and cardiac troponin T (cTnT) and risk of incident HF in older men. Methods and results Prospective study of 3242 men aged 60–79 years without prevalent HF or myocardial infarction followed up for an average period of 13 years, in whom 211 incident HF cases occurred. Incident HF was examined in relation to % predicted FEV1 and FVC. The Global Initiative on Obstructive Lung Diseases spirometry criteria were used to define airway obstruction. Reduced FEV1, but not FVC in the normal range, was significantly associated with increased risk of HF after adjustment for established HF risk factors including inflammation. The adjusted HRs comparing men in the 6–24th percentile with the highest quartile were 1.91 (1.24 to 2.94) and 1.30 (0.86 to 1.96) for FEV1 and FVC, respectively. FEV1 and FVC were inversely associated with NT-proBNP and cTnT, although the association between FEV1 and incident HF remained after adjustment for NT-proBNP and cTnT. Compared with normal subjects (FEV1/FVC ≥0.70 and FVC≥80%), moderate or severe (FEV1/FVC <0.70 and FEV1 <80%) airflow obstruction was independently associated with HF ((adjusted relative risk 1.59 (1.08 to 2.33)). Airflow restriction (FEV1/FVC ≥0.70 and FVC <80%) was not independently associated with HF. Conclusions Reduced FEV1 reflecting airflow obstruction is associated with cardiac dysfunction and increased risk of incident HF in older men. PMID:26811343

  18. Positive airway pressure improves nocturnal beat-to-beat blood pressure surges in obesity hypoventilation syndrome with obstructive sleep apnea.

    PubMed

    Carter, Jason R; Fonkoue, Ida T; Grimaldi, Daniela; Emami, Leila; Gozal, David; Sullivan, Colin E; Mokhlesi, Babak

    2016-04-01

    Positive airway pressure (PAP) treatment has been shown to have a modest effect on ambulatory blood pressure (BP) in patients with obstructive sleep apnea (OSA). However, there is a paucity of data on the effect of PAP therapy on rapid, yet significant, BP swings during sleep, particularly in obesity hypoventilation syndrome (OHS). The present study hypothesizes that PAP therapy will improve nocturnal BP on the first treatment night (titration PAP) in OHS patients with underlying OSA, and that these improvements will become more significant with 6 wk of PAP therapy. Seventeen adults (7 men, 10 women; age 50.4 ± 10.7 years, BMI 49.3 ± 2.4 kg/m(2)) with OHS and clinically diagnosed OSA participated in three overnight laboratory visits that included polysomnography and beat-to-beat BP monitoring via finger plethysmography. Six weeks of PAP therapy, but not titration PAP, lowered mean nocturnal BP. In contrast, when nocturnal beat-to-beat BPs were aggregated into bins consisting of at least three consecutive cardiac cycles with a >10 mmHg BP surge (i.e., Δ10-20, Δ20-30, Δ30-40, and Δ>40 mmHg), titration, and 6-wk PAP reduced the number of BP surges per hour (time × bin,P< 0.05). PAP adherence over the 6-wk period was significantly correlated to reductions in nocturnal systolic (r= 0.713,P= 0.001) and diastolic (r= 0.497,P= 0.043) BP surges. Despite these PAP-induced improvements in nocturnal beat-to-beat BP surges, 6 wk of PAP therapy did not alter daytime BP. In conclusion, PAP treatment reduces nocturnal beat-to-beat BP surges in OHS patients with underlying OSA, and this improvement in nocturnal BP regulation was greater in patients with higher PAP adherence. PMID:26818059

  19. Estimating the Time Interval Between Exposure to the World Trade Center Disaster and Incident Diagnoses of Obstructive Airway Disease

    PubMed Central

    Glaser, Michelle S.; Webber, Mayris P.; Zeig-Owens, Rachel; Weakley, Jessica; Liu, Xiaoxue; Ye, Fen; Cohen, Hillel W.; Aldrich, Thomas K.; Kelly, Kerry J.; Nolan, Anna; Weiden, Michael D.; Prezant, David J.; Hall, Charles B.

    2014-01-01

    Respiratory disorders are associated with occupational and environmental exposures. The latency period between exposure and disease onset remains uncertain. The World Trade Center (WTC) disaster presents a unique opportunity to describe the latency period for obstructive airway disease (OAD) diagnoses. This prospective cohort study of New York City firefighters compared the timing and incidence of physician-diagnosed OAD relative to WTC exposure. Exposure was categorized by WTC arrival time as high (on the morning of September 11, 2001), moderate (after noon on September 11, 2001, or on September 12, 2001), or low (during September 13–24, 2001). We modeled relative rates and 95% confidence intervals of OAD incidence by exposure over the first 5 years after September 11, 2001, estimating the times of change in the relative rate with change point models. We observed a change point at 15 months after September 11, 2001. Before 15 months, the relative rate for the high- versus low-exposure group was 3.96 (95% confidence interval: 2.51, 6.26) and thereafter, it was 1.76 (95% confidence interval: 1.26, 2.46). Incident OAD was associated with WTC exposure for at least 5 years after September 11, 2001. There were higher rates of new-onset OAD among the high-exposure group during the first 15 months and, to a lesser extent, throughout follow-up. This difference in relative rate by exposure occurred despite full and free access to health care for all WTC-exposed firefighters, demonstrating the persistence of WTC-associated OAD risk. PMID:24980522

  20. Patients with obstructive sleep apnea exhibit genioglossus dysfunction that is normalized after treatment with continuous positive airway pressure.

    PubMed

    Carrera, M; Barbé, F; Sauleda, J; Tomás, M; Gómez, C; Agustí, A G

    1999-06-01

    Obstructive sleep apnea syndrome (OSAS) is characterized by repetitive episodes of pharyngeal closure during sleep. The pathogenesis of OSAS is unclear. We hypothesized that the genioglossus (GG), the most important pharyngeal dilator muscle, would be abnormal in patients with OSAS. Further, because treatment with continuous positive airway pressure (CPAP) is very effective clinically in these patients, we investigated the effects of CPAP upon the structure and function of the GG. We studied 16 patients with OSAS (nine of them at diagnosis and seven after having been under treatment with CPAP for at least 1 yr) and 11 control subjects in whom OSAS was excluded clinically. A biopsy of the GG was obtained in each subject, mounted in a tissue bath, and stimulated through platinum electrodes. The following measurements were obtained: maximal twitch tension, contraction time, half-relaxation time, the force-frequency relationship, and the response to a fatiguing protocol. The percentage of type I ("slow twitch") and type II ("fast twitch") fibers was also quantified. Patients with OSAS showed a greater GG fatigability than did control subjects (ANOVA, p < 0.001). Interestingly, this abnormality was entirely corrected by CPAP. Likewise, the percentage of type II fibers was significantly higher in patients with OSAS (59 +/- 4%) than in control subjects (39 +/- 4%, p < 0.001) and, again, these structural changes were corrected by CPAP (40 +/- 3%, p < 0.001). These results show that the function and structure of the GG is abnormal in patients with OSAS. Because these abnormalities are corrected by CPAP, we suggest that they are likely a consequence, not a cause, of the disease. PMID:10351945

  1. Estimating the time interval between exposure to the World Trade Center disaster and incident diagnoses of obstructive airway disease.

    PubMed

    Glaser, Michelle S; Webber, Mayris P; Zeig-Owens, Rachel; Weakley, Jessica; Liu, Xiaoxue; Ye, Fen; Cohen, Hillel W; Aldrich, Thomas K; Kelly, Kerry J; Nolan, Anna; Weiden, Michael D; Prezant, David J; Hall, Charles B

    2014-08-01

    Respiratory disorders are associated with occupational and environmental exposures. The latency period between exposure and disease onset remains uncertain. The World Trade Center (WTC) disaster presents a unique opportunity to describe the latency period for obstructive airway disease (OAD) diagnoses. This prospective cohort study of New York City firefighters compared the timing and incidence of physician-diagnosed OAD relative to WTC exposure. Exposure was categorized by WTC arrival time as high (on the morning of September 11, 2001), moderate (after noon on September 11, 2001, or on September 12, 2001), or low (during September 13-24, 2001). We modeled relative rates and 95% confidence intervals of OAD incidence by exposure over the first 5 years after September 11, 2001, estimating the times of change in the relative rate with change point models. We observed a change point at 15 months after September 11, 2001. Before 15 months, the relative rate for the high- versus low-exposure group was 3.96 (95% confidence interval: 2.51, 6.26) and thereafter, it was 1.76 (95% confidence interval: 1.26, 2.46). Incident OAD was associated with WTC exposure for at least 5 years after September 11, 2001. There were higher rates of new-onset OAD among the high-exposure group during the first 15 months and, to a lesser extent, throughout follow-up. This difference in relative rate by exposure occurred despite full and free access to health care for all WTC-exposed firefighters, demonstrating the persistence of WTC-associated OAD risk. PMID:24980522

  2. Restoring the salivary cortisol awakening response through nasal continuous positive airway pressure therapy in obstructive sleep apnea.

    PubMed

    Ghiciuc, Cristina Mihaela; Dima Cozma, Lucia Corina; Bercea, Raluca Mihaela; Lupusoru, Catalina Elena; Mihaescu, Traian; Szalontay, Andreea; Gianfreda, Angela; Patacchioli, Francesca Romana

    2013-10-01

    Partial and largely conflicting data are currently available on the interplay between obstructive sleep apnea (OSA) and hypothalamus-pituitary-adrenal axis (HPA) activity in adult obese men. This study was performed to evaluate the daily trajectories of salivary cortisol, specifically with respect to the salivary cortisol awakening response (CAR), a common method used to assess HPA axis activity. The main findings of this study were that adult male obese subjects who were newly diagnosed with severe OSA showed the following: (1) a flattening of the CAR; (2) levels of cortisol at awakening that were lower than those of the controls; and (3) maintenance of the physiological circadian activity of the HPA axis, with the highest hormone concentrations produced in the morning and the lowest in the evening. This study was also designed to investigate the effects of 3 and 6 mos of treatment with continuous airways positive pressure (CPAP). CPAP use resulted in a significant recovery of the sleep patterns disrupted by OSA; moreover, mild neuropsychological signs of depression and anxiety in severe OSA patients were concomitantly progressively improved by CPAP treatment. Furthermore, this study reports that 3 and 6 mos of CPAP therapy restored the presence of CAR and was able to significantly reduce the difference in the morning cortisol levels between the OSA and control groups. In conclusion, we report here that compared with obese nonapneic matched controls, OSA patients present a dysregulation of HPA axis activity, as shown by the flattening of the diurnal pattern of cortisol production in response to repeated challenge due to hypoxia and sleep fragmentation. This dysregulation was especially detectable in the first hour after awakening and restored after 3 and 6 mos of treatment with CPAP. PMID:23859257

  3. Long-term exposure of adults to outdoor air pollution is associated with increased airway obstruction and higher prevalence of bronchial hyperresponsiveness

    SciTech Connect

    Jammres, Y.; Delpierre, S.; Burnet, H.; Delvolgo, M.J.; Humbert-Tena, C.

    1998-11-01

    The authors studied the association between long-term exposure to outdoor air pollution and the severity of obstructive pulmonary disease and prevalence of bronchial hyperreactivity to {beta}2 agonists in two groups of adult patients who were of similar ages and who had similar smoking habits. The subjects lived in downtown districts or in the outer suburbs of Marseilles, the neighborhood that contained air samplers. The regions were similar with respect to sulfur dioxide levels, but levels of nitric oxides and particulate matter were higher in the downtown area than the suburbs. The authors assessed airway obstruction, as determined by a decrease in forced expiratory volume in 1 s, mean forced expiratory flow measured between 25% and 75% of vital capacity, and an elevated value of central airway resistance. The authors tested the changes in these variables induced by inhalation of a {beta}2 agonist. Baseline lung function was altered more significantly in both male and female patients who lived in downtown Marseilles than in those who resided in the suburbs, and the differences persisted regardless of the season during which the study occurred. Prevalence of bronchial hyperreactivity and symptoms of asthma were higher in the downtown than suburban male subjects. The results of this study suggest that an association exists between actual environmental exposure to outdoor air pollution and respiratory effects in sensitive adults represented by patients with chronic obstructive pulmonary disease or asthma.

  4. Lack of efficacy of pre bronchoscopy inhaled salbutamol on symptoms and lung functions in patients with pre-existing airway obstruction

    PubMed Central

    Mohan, Anant; Momin, Indrajit; Poulose, Rosemary; Mohan, Charu; Madan, Karan; Hadda, Vijay; Guleria, Randeep; Pandey, RM

    2016-01-01

    Background: Fiberoptic bronchoscopy (FOB) may exaggerate symptoms and lung functions in patients with pre-existing airway obstruction. Interventions which can alleviate or minimize this procedure-related bronchospasm, especially in this high-risk group are, therefore, required. Methods: A double-blinded randomized controlled trial was conducted to evaluate the efficacy of 400 μg of inhaled salbutamol on patients with spirometric evidence of airflow obstruction planned for FOB. Patient's dyspnea, procedure tolerability, and change in spirometry were assessed before and after the procedure. Results: A total of 50 patients were enrolled (78% males), with a mean (standard deviation) age of 49.8 (6.2) years. There was a significant fall in % predicted FEV1 within each group compared to their respective pre-bronchoscopy values. However, no significant difference in the % predicted or absolute FEV1 level was observed between the two groups. Similarly, although both groups experienced increased dyspnea immediately following FOB, this difference was not significant between the two groups either on the Borg or visual analog scale scales. Pre-FOB anxiety levels and the tolerability of the procedure as assessed by the bronchoscopist were similar in both groups. Conclusion: FOB in patients with pre-existing airway obstruction aggravates cough and dyspnea, with a concomitant decline in FEV1 and FVC. The administration of pre-FOB inhaled salbutamol does not have any significant beneficial effect on procedure-related outcomes. PMID:27578926

  5. The pathology of chronic obstructive pulmonary disease.

    PubMed

    Hogg, James C; Timens, Wim

    2009-01-01

    The pathogenesis of chronic obstructive pulmonary disease (COPD) is based on the innate and adaptive inflammatory immune response to the inhalation of toxic particles and gases. Although tobacco smoking is the primary cause of this inhalation injury, many other environmental and occupational exposures contribute to the pathology of COPD. The immune inflammatory changes associated with COPD are linked to a tissue-repair and -remodeling process that increases mucus production and causes emphysematous destruction of the gas-exchanging surface of the lung. The common form of emphysema observed in smokers begins in the respiratory bronchioles near the thickened and narrowed small bronchioles that become the major site of obstruction in COPD. The mechanism(s) that allow small airways to thicken in such close proximity to lung tissue undergoing emphysematous destruction remains a puzzle that needs to be solved. PMID:18954287

  6. A soluble secreted glycoprotein (eCLCA1) is overexpressed due to goblet cell hyperplasia and metaplasia in horses with recurrent airway obstruction.

    PubMed

    Range, F; Mundhenk, L; Gruber, A D

    2007-11-01

    The equine putative chloride channel protein eCLCA1 is thought to be critically involved in the pathogenesis of recurrent airway obstruction (RAO) via modulation of the hydration of airway mucins. A recent study revealed a strong increase of eCLCA1 messenger ribonucleic acid (mRNA) in the lungs of horses with RAO. In this study, eCLCA1 protein and mRNA expression were quantified in airway goblet cells of 9 horses affected with RAO and 9 control horses by using immunohistochemistry and laser microdissection followed by real-time quantitative reverse transcription polymerase chain reaction, respectively. Horses affected by RAO had strong goblet cell metaplasia in bronchioles and goblet cell hyperplasia in bronchi and the trachea. Expression of the eCLCA1 protein was tightly linked to all airway goblet cells in both groups. No differences were detected in the ratio of eCLCA1 mRNA copy numbers to the mRNA copy numbers of the housekeeping gene EF-1a per goblet cell between horses affected with RAO and unaffected horses, suggesting that the increase in eCLCA1 expression is because of increased numbers of goblet cells and not transcriptional upregulation of the eCLCA1 gene. In addition, biochemical analyses of the eCLCA1 protein after in vitro translation and heterologous expression in cultured cells revealed that eCLCA1 is a secreted glycoprotein and not an integral membrane protein. Taken together, the results suggest that eCLCA1 mediates its effect as a soluble constituent of airway mucins that is overexpressed in RAO airways because of goblet cell hyperplasia and metaplasia, not transcriptional upregulation. PMID:18039903

  7. Intranasal curcumin ameliorates airway inflammation and obstruction by regulating MAPKinase activation (p38, Erk and JNK) and prostaglandin D2 release in murine model of asthma.

    PubMed

    Subhashini; Chauhan, Preeti S; Dash, D; Paul, B N; Singh, Rashmi

    2016-02-01

    Asthma, a multifactorial, chronic inflammatory disease encompasses multiple complex pathways releasing number of mediators by activated mast cells, eosinophils and T lymphocytes, leading to its severity. Presently available medications are associated with certain limitations, and hence, it is imperative to search for anti-inflammatory drug preferably targeting signaling cascades involved in inflammation thereby suppressing inflammatory mediators without any side effect. Curcumin, an anti-inflammatory molecule with potent anti-asthmatic potential has been found to suppress asthmatic features by inhibiting airway inflammation and bronchoconstriction if administered through nasal route. The present study provides new insight towards anti-asthmatic potential of intranasal curcumin at lower doses (2.5 and 5.0mg/kg) in Balb/c mice sensitized and challenged with ovalbumin (OVA) which is effective in inhibiting airway inflammation. These investigations suggest that intranasal curcumin (2.5 and 5.0mg/kg) regulates airway inflammation and airway obstruction mainly by modulating cytokine levels (IL-4, 5, IFN-ƴ and TNF-α) and sPLA2 activity thereby inhibiting PGD2 release and COX-2 expression. Further, the suppression of p38 MAPK, ERK 42/44 and JNK54/56 activation elucidate the mechanism behind the inhibitory role of intranasal curcumin in asthma progression. Thus, curcumin could be better alternative for the development of nasal formulations and inhalers in near future. PMID:26761722

  8. Effect of telemetric monitoring in the first 30 days of continuous positive airway pressure adaptation for obstructive sleep apnoea syndrome - a controlled pilot study.

    PubMed

    Frasnelli, Matthias; Baty, Florent; Niedermann, Jolanda; Brutsche, Martin H; Schoch, Otto D

    2016-06-01

    Obstructive sleep apnoea syndrome (OSAS) is characterised by repetitive collapse of the upper airway during sleep. Continuous positive airway pressure (CPAP) applied via a mask is the standard treatment for OSAS. CPAP adherence is crucial in therapy to prevent the deleterious consequences of OSAS. We hypothesised that a combination of supervision by telemetry together with targeted telephone support in the first month of CPAP would increase CPAP adherence and treatment success. A total of 113 OSAS patients followed by telemetry-triggered interventions used the device for 5.3 h/night on 28/30 nights, significantly more than the 110 OSAS patients in the control group with 4.6 h/night and 27/30 nights. Telemetry-triggered interventions have a significant impact on adherence rate in early CPAP treatment. These results can be reached with an acceptable additional effort. PMID:26253747

  9. Structure and Function of the Mucus Clearance System of the Lung

    PubMed Central

    Button, Brenda M.; Button, Brian

    2013-01-01

    In cystic fibrosis (CF), a defect in ion transport results in thick and dehydrated airway mucus, which is difficult to clear, making such patients prone to chronic inflammation and bacterial infections. Physiotherapy using a variety of airway clearance techniques (ACTs) represents a key treatment regime by helping clear the airways of thickened, adhered, mucus and, thus, reducing the impact of lung infections and improving lung function. This article aims to bridge the gap between our understanding of the physiological effects of mechanical stresses elicited by ACTs on airway epithelia and the reported effectiveness of ACTs in CF patients. In the first part of this review, the effects of mechanical stress on airway epithelia are discussed in relation to changes in ion transport and stimulation in airway surface layer hydration. The second half is devoted to detailing the most commonly used ACTs to stimulate the removal of mucus from the airways of patients with CF. PMID:23751214

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

    PubMed

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

    2007-11-01

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

  11. Predictors of Long-Term Adherence to Continuous Positive Airway Pressure Therapy in Patients with Obstructive Sleep Apnea and Cardiovascular Disease in the SAVE Study

    PubMed Central

    Chai-Coetzer, Ching Li; Luo, Yuan-Ming; Antic, Nick A.; Zhang, Xi-Long; Chen, Bao-Yuan; He, Quan-Ying; Heeley, Emma; Huang, Shao-Guang; Anderson, Craig; Zhong, Nan-Shan; McEvoy, R. Doug

    2013-01-01

    Study Objectives: To determine the clinical variables that best predict long- term continuous positive airway pressure (CPAP) adherence among patients with cardiovascular disease who have obstructive sleep apnea (OSA). Design: 12-mo prospective within-trial observational study. Setting: Centers in China, Australia, and New Zealand participating in the Sleep Apnea cardioVascular Endpoints (SAVE) study. Patients: There were 275 patients age 45-70 y with cardiovascular disease (i.e., previously documented transient ischemic attack, stroke, or coronary artery disease) and OSA (4% oxygen desaturation index (ODI) > 12) who were randomized into the CPAP arm of the SAVE trial prior to July 1, 2010. Methods: Age, sex, country of residence, type of cardiovascular disease, baseline ODI, severity of sleepiness, and Hospital Anxiety and Depression Scale (HADS) scores plus CPAP side effects and adherence at 1 mo were entered in univariate analyses in an attempt to identify factors predictive of CPAP adherence at 12 mo. Variables with P < 0.2 were then included in a multivariate analysis using a linear mixed model with sites as a random effect and 12-mo CPAP use as the dependent outcome variable. Measurements and Results: CPAP adherence at 1, 6, and 12 mo was (mean ± standard deviation) 4.4 ± 2.0, 3.8 ± 2.3, and 3.3 ± 2.4 h/night, respectively. CPAP use at 1 mo (effect estimate ± standard error, 0.65 ± 0.07 per h increase, P < 0.001) and side effects at 1 mo (-0.24 ± 0.092 per additional side effect, P = 0.009) were the only independent predictors of 12- mo CPAP adherence. Conclusion: Continuous positive airway pressure use in patients with coexisting cardiovascular disease and moderate to severe obstructive sleep apnea decreases significantly over 12 months. This decline can be predicted by early patient experiences with continuous positive airway pressure (i.e., adherence and side effects at 1 month), raising the possibility that intensive early interventions could

  12. Model for assessing bronchial mucus transport

    SciTech Connect

    Agnew, J.E.; Bateman, J.R.M.; Pavia, D.; Clarke, S.W.

    1984-02-01

    The authors propose a scheme for the assessment of regional mucus transport using inhaled Tc-99m aerosol particles and quantitative analysis of serial gamma-camera images. The model treats input to inner and intermediate lung regions as the total of initial deposition there plus subsequent transport into these regions from more peripheral airways. It allows for interregional differences in the proportion of particles deposited on the mucus-bearing conducting airways, and does not require a gamma image 24 hr after particle inhalation. Instead, distribution of particles reaching the respiratory bronchioles or alveoli is determined from a Kr-81m ventilation image, while the total amount of such deposition is obtained from 24-hr Tc-99m retention measured with a sensitive counter system. The model is applicable to transport by mucociliary action or by cough, and has been tested in ten normal and ten asthmatic subjects.

  13. Nanoparticle diffusion in respiratory mucus from humans without lung disease

    PubMed Central

    Schuster, Benjamin S.; Suk, Jung Soo; Woodworth, Graeme F.; Hanes, Justin

    2013-01-01

    A major role of respiratory mucus is to trap inhaled particles, including pathogens and environmental particulates, to limit body exposure. Despite the tremendous health implications, how particle size and surface chemistry affect mobility in respiratory mucus from humans without lung disease is not known. We prepared polymeric nanoparticles densely coated with low molecular weight polyethylene glycol (PEG) to minimize muco-adhesion, and compared their transport to that of uncoated particles in human respiratory mucus, which we collected from the endotracheal tubes of surgical patients with no respiratory comorbidities. We found that 100 and 200 nm diameter PEG-coated particles rapidly penetrated respiratory mucus, at rates exceeding their uncoated counterparts by approximately 15- and 35-fold, respectively. In contrast, PEG-coated particles ≥ 500 nm in diameter were sterically immobilized by the mucus mesh. Thus, even though respiratory mucus is a viscoelastic solid at the macroscopic level (as measured using a bulk rheometer), nanoparticles that are sufficiently small and muco-inert can penetrate the mucus as if it were primarily a viscous liquid. These findings help elucidate the barrier properties of respiratory mucus and provide design criteria for therapeutic nanoparticles capable of penetrating mucus to approach the underlying airway epithelium. PMID:23384790

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

    PubMed

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

    2012-02-01

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

  15. Erectile Dysfunction and Sexual Hormone Levels in Men With Obstructive Sleep Apnea: Efficacy of Continuous Positive Airway Pressure.

    PubMed

    Zhang, Xiao-Bin; Lin, Qi-Chang; Zeng, Hui-Qing; Jiang, Xing-Tang; Chen, Bo; Chen, Xiao

    2016-01-01

    In this study, the prevalence of erectile dysfunction (ED) and serum sexual hormone levels were evaluated in men with obstructive sleep apnea (OSA). In these patients, the efficacy of continuous positive airway pressure (CPAP) was determined. The 207 men (mean age 44.0 ± 11.1 years) enrolled in the study were stratified within four groups based on their apnea-hypopnea index score: simple snoring (n = 32), mild OSA (n = 29), moderate OSA (n = 38), and severe OSA (n = 108). The International Index of Erectile Dysfunction-5 (IIEF-5) score was obtained from each patient, and blood samples for the analysis of sexual hormones (prolactin, luteotropin, follicle-stimulating hormone, estradiol, progestin, and testosterone) were drawn in the morning after polysomnography. The IIEF-5 test and serum sexual hormone measurements were repeated after 3 months of CPAP treatment in 53 men with severe OSA. The prevalence of ED was 60.6 % in OSA patients overall and 72.2 % in those with severe OSA. Compared with the simple snoring group, patients with severe OSA had significantly lower testosterone levels (14.06 ± 5.62 vs. 17.02 ± 4.68, p = .018) and lower IIEF-5 scores (16.33 ± 6.50 vs. 24.09 ± 1.94, p = .001). The differences in the other sexual hormones between groups were not significant. After 3 months of CPAP treatment, there were no significant changes in sexual hormone levels, but the IIEF-5 score had improved significantly (18.21 ± 4.05 vs. 19.21 ± 3.86, p = .001). Severe OSA patients have low testosterone concentration and high ED prevalence. IIEF-5 scores increased significantly after CPAP treatment, but there was no effect on serum testosterone levels. PMID:26370402

  16. Lung cancer mortality and airways obstruction among metal miners exposed to silica and low levels of radon daughters.

    PubMed

    Carta, P; Cocco, P; Picchiri, G

    1994-04-01

    Starting from a cross-sectional survey in 1973, the mortality of two cohorts of Sardinian metal miners was followed through December 31, 1988. In mine A, the quartz concentration in respirable dust ranged between 0.2% and 2.0% and the exposure to radon daughters averaged 0.13 working level (WL), with the highest estimated cumulative exposure around 80-120 WLM. In mine B, the silica content was much higher (6.5-29%), but exposure to radon daughters was significantly lower than in mine A. More than 98% of the overall work force in 1973 (1,741 miners) entered the cohort, providing 25,842.5 person-years. Smoking, occupational history, chest radiographs, and lung function tests were available for the cohort members at admission. Mortality for all causes was slightly lower than expected. A significant excess for nonmalignant chronic respiratory diseases was noticed in both mines. Twenty-four subjects died of lung cancer, 17 from mine A (SMR: 128; 95% confidence interval [CI]: 75-205) and 7 from mine B (SMR: 85; 95% CI: 34-175). The SMR for lung cancer was highest among the underground workers from mine A (SMR: 148; 95% CI: 74-265), with a significant upward trend by duration of employment in underground jobs. Mine B underground miners showed lung cancer SMRs close to 100 without a significant trend by duration of employment. Among underground miners with spirometric airways obstruction in 1973, those from mine A showed the highest risk (SMR: 316; 95% CI: 116-687). The relationship did not change after adjusting for age and smoking. Based on the present findings, crystalline silica per se does not appear to affect lung cancer mortality. A slight association between lung cancer mortality and exposure to radon daughters, though within relatively low levels, may be considered for underground miners from mine A. Impaired pulmonary function may be an independent predictor of lung cancer and an important risk factor enhancing the residence time of inhaled carcinogens, i

  17. Prevalence of obstructive airway disease by spirometric indices in non-smoker subjects with IHD and HTN

    PubMed Central

    Patil, Virendra C.; Pujari, Bhupal N.; Patil, Harsha V.; Munjal, Amit; Agrawal, Vaibhav

    2012-01-01

    Background: Recent studies have found that there is a strong association between ischemic heart disease (IHD) and hypertension (HTN) with spirometric indices. Aims: To study the prevalence of obstructive airway disease (OAD) in non-smoker subjects with IHD and HTN and to compare them with healthy population. Settings and Design: This was a prospective, case–control, and observational study. Subjects and Methods: A total of 100 patients (cases) (n = 100) admitted in medicine department were recruited for this study. Controls (n = 100) were apparently healthy age- and sex-matched without HTN and IHD, recruited from March 2007 to July 2008. All eligible subjects were subjected to spirometric examination on a turbine-based spirometer (MIR spirolab-II) according to ATS/ERS guidelines. Forced expiratory volume/forced vital capacity (FEV1/FVC) ratio <70% was used to make a diagnosis of OAD. Statistical Analysis Used: All analyses were carried out using Statistical Software Package for Social Sciences trial version (SPSS 10 version). Results: Out of 100 cases, 18 were with FEV1/FVC ratio <70% (OAD) and 82 had >70% FEV1/FVC ratio. Out of 100 controls, 2 were with FEV1/FVC ratio <70% (OAD) and 98 had >70% FEV1/FVC ratio. Eleven patients out of 66 from the case population with HTN had FEV1/FVC ratio <70% (Odds ratio 8.044). Prevalence of OAD in the hypertensive individuals was 16.66%. Twelve patients out of 62 from the case population with IHD had FEV1/FVC ratio <70% (Odds ratio of 9.333). Prevalence of OAD in the IHD individuals was 19.35%. In multiple correlation results for case population, when pulmonary function test variables were correlated with various dependant (age) and independent variables [HTN, IHD, height, weight, body mass index (BMI)], they were significantly reduced (P = 0.00017). In multivariate analysis (MANOVA), spirometric variables like FEV1, FEV1/FVC%, FVC, forced expiratory flow (FEF) 25–75%, and peak expiratory flow rate (PEFR) were compared with

  18. 1,8-Cineol Reduces Mucus-Production in a Novel Human Ex Vivo Model of Late Rhinosinusitis

    PubMed Central

    Greiner, Johannes F. W.; Müller, Janine; Brotzmann, Viktoria; Ebmeyer, Jörg

    2015-01-01

    Inflammatory diseases of the respiratory system such as rhinosinusitis, chronic obstructive pulmonary disease, or bronchial asthma are strongly associated with overproduction and hypersecretion of mucus lining the epithelial airway surface. 1,8-cineol, the active ingredient of the pharmaceutical drug Soledum, is commonly applied for treating such inflammatory airway diseases. However, its potential effects on mucus overproduction still remain unclear.In the present study, we successfully established ex vivo cultures of human nasal turbinate slices to investigate the effects of 1,8-cineol on mucus hypersecretion in experimentally induced rhinosinusitis. The presence of acetyl-α-tubulin-positive cilia confirmed the integrity of the ex vivo cultured epithelium. Mucin-filled goblet cells were also detectable in nasal slice cultures, as revealed by Alcian Blue and Periodic acid-Schiff stainings. Treatment of nasal slice cultures with lipopolysaccharides mimicking bacterial infection as observed during late rhinosinusitis led to a significantly increased number of mucin-filled goblet cells. Notably, the number of mucin-filled goblet cells was found to be significantly decreased after co-treatment with 1,8-cineol. On a molecular level, real time PCR-analysis further showed 1,8-cineol to significantly reduce the expression levels of the mucin genes MUC2 and MUC19 in close association with significantly attenuated NF-κB-activity. In conclusion, we demonstrate for the first time a 1,8-cineol-dependent reduction of mucin-filled goblet cells and MUC2-gene expression associated with an attenuated NF-κB-activity in human nasal slice cultures. Our findings suggest that these effects partially account for the clinical benefits of 1,8-cineol-based therapy during rhinosinusitis. Therefore, topical application of 1,8-cineol may offer a novel therapeutic approach to reduce bacteria-induced mucus hypersecretion. PMID:26207629

  19. The pathophysiological mechanisms underlying mucus hypersecretion induced by cold temperatures in cigarette smoke-exposed rats.

    PubMed

    Li, Min-Chao; Yang, Gang; Zhou, Xiang-Dong; Tselluyko, Sergey; Perelman, Juliy M

    2014-01-01

    In a recent study, we demonstrated that transient receptor potential melastatin 8 (TRPM8), a calcium-permeable cation channel that is activated by cold temperatures, is localized in the bronchial epithelium and is upregulated in subjects with chronic obstructive pulmonary disease, which causes them to be more sensitive to cold air. In the present study, we found that exposure to cold temperatures induced ciliary ultrastructural anomalies and mucus accumulation on the epithelial surface. Male Sprague-Dawley rats were exposed to cold temperatures to determine the effects of cold air on ultrastructural changes in cilia and the airway epithelial surface. The rats were also exposed to cigarette smoke and/or cold temperatures to determine the effects of smoke and cold air on TRPM8 expression and the role of cold air in cigarette smoke-induced mucus hypersecretion. Following real-time RT-PCR and western blot analysis, we observed a high expression of TRPM8 mRNA and protein in the bronchial tissue following cigarette smoke inhalation. As shown by ELISA, concurrent cold air enhanced the levels of mucin 5AC (MUC5AC) protein, as well as those of inflammatory factors [tumor necrosis factor (TNF)-α and interleukin (IL)-8] that were induced by cigarette smoke inhalation to a greater extent than stimulation with separate stimuli (cold air and cigarette smoke separately). The results suggest that cold air stimuli are responsible for the ultrastructural abnormalities of bronchial cilia, which contribute to abnormal mucus clearance. In addition, cold air synergistically amplifies cigarette smoke-induced mucus hypersecretion and the production of inflammatory factors through the elevated expression of the TRPM8 channel that is initiated by cigarette smoke inhalation. PMID:24154796

  20. Mycoplasma pneumoniae Modulates STAT3-STAT6/EGFR-FOXA2 Signaling To Induce Overexpression of Airway Mucins

    PubMed Central

    Hao, Yonghua; Kuang, Zhizhou; Jing, Jia; Miao, Jinfeng; Mei, Li Yu; Lee, Ryan J.; Kim, Susie; Choe, Shawn; Krause, Duncan C.

    2014-01-01

    Aberrant mucin secretion and accumulation in the airway lumen are clinical hallmarks associated with various lung diseases such as asthma, chronic obstructive pulmonary disease, and cystic fibrosis. Mycoplasma pneumoniae, long appreciated as one of the triggers of acute exacerbations of chronic pulmonary diseases, has recently been reported to promote excessive mucus secretion. However, the mechanism of mucin overproduction induced by M. pneumoniae remains unclear. This study aimed to determine the mechanism by which M. pneumoniae induces mucus hypersecretion by using M. pneumoniae infection of mouse lungs, human primary bronchial epithelial (NHBE) cells cultured at the air-liquid interface, and the conventionally cultured airway epithelial NCI-H292 cell line. We demonstrated that M. pneumoniae induced the expression of mucins MUC5AC and MUC5B by activating the STAT6-STAT3 and epidermal growth factor receptor (EGFR) signal pathways, which in turn downregulated FOXA2, a transcriptional repressor of mucin biosynthesis. The upstream stimuli of these pathways, including interleukin-4 (IL-4), IL-6, and IL-13, increased dramatically upon exposure to M. pneumoniae. Inhibition of the STAT6, STAT3, and EGFR signaling pathways significantly restored the expression of FOXA2 and attenuated the expression of airway mucins MUC5AC and MUC5B. Collectively, these studies demonstrated that M. pneumoniae induces airway mucus hypersecretion by modulating the STAT/EGFR-FOXA2 signaling pathways. PMID:25287927

  1. Muc5b is required for airway defence

    NASA Astrophysics Data System (ADS)

    Roy, Michelle G.; Livraghi-Butrico, Alessandra; Fletcher, Ashley A.; McElwee, Melissa M.; Evans, Scott E.; Boerner, Ryan M.; Alexander, Samantha N.; Bellinghausen, Lindsey K.; Song, Alfred S.; Petrova, Youlia M.; Tuvim, Michael J.; Adachi, Roberto; Romo, Irlanda; Bordt, Andrea S.; Bowden, M. Gabriela; Sisson, Joseph H.; Woodruff, Prescott G.; Thornton, David J.; Rousseau, Karine; de La Garza, Maria M.; Moghaddam, Seyed J.; Karmouty-Quintana, Harry; Blackburn, Michael R.; Drouin, Scott M.; Davis, C. William; Terrell, Kristy A.; Grubb, Barbara R.; O'Neal, Wanda K.; Flores, Sonia C.; Cota-Gomez, Adela; Lozupone, Catherine A.; Donnelly, Jody M.; Watson, Alan M.; Hennessy, Corinne E.; Keith, Rebecca C.; Yang, Ivana V.; Barthel, Lea; Henson, Peter M.; Janssen, William J.; Schwartz, David A.; Boucher, Richard C.; Dickey, Burton F.; Evans, Christopher M.

    2014-01-01

    Respiratory surfaces are exposed to billions of particulates and pathogens daily. A protective mucus barrier traps and eliminates them through mucociliary clearance (MCC). However, excessive mucus contributes to transient respiratory infections and to the pathogenesis of numerous respiratory diseases. MUC5AC and MUC5B are evolutionarily conserved genes that encode structurally related mucin glycoproteins, the principal macromolecules in airway mucus. Genetic variants are linked to diverse lung diseases, but specific roles for MUC5AC and MUC5B in MCC, and the lasting effects of their inhibition, are unknown. Here we show that mouse Muc5b (but not Muc5ac) is required for MCC, for controlling infections in the airways and middle ear, and for maintaining immune homeostasis in mouse lungs, whereas Muc5ac is dispensable. Muc5b deficiency caused materials to accumulate in upper and lower airways. This defect led to chronic infection by multiple bacterial species, including Staphylococcus aureus, and to inflammation that failed to resolve normally. Apoptotic macrophages accumulated, phagocytosis was impaired, and interleukin-23 (IL-23) production was reduced in Muc5b-/- mice. By contrast, in mice that transgenically overexpress Muc5b, macrophage functions improved. Existing dogma defines mucous phenotypes in asthma and chronic obstructive pulmonary disease (COPD) as driven by increased MUC5AC, with MUC5B levels either unaffected or increased in expectorated sputum. However, in many patients, MUC5B production at airway surfaces decreases by as much as 90%. By distinguishing a specific role for Muc5b in MCC, and by determining its impact on bacterial infections and inflammation in mice, our results provide a refined framework for designing targeted therapies to control mucin secretion and restore MCC.

  2. Muc5b Is Required for Airway Defense

    PubMed Central

    Roy, Michelle G.; Livraghi-Butrico, Alessandra; Fletcher, Ashley A.; McElwee, Melissa M.; Evans, Scott E.; Boerner, Ryan M.; Alexander, Samantha N.; Bellinghausen, Lindsey K.; Song, Alfred S.; Petrova, Youlia M.; Tuvim, Michael J.; Adachi, Roberto; Romo, Irlanda; Bordt, Andrea S.; Gabriela Bowden, M.; Sisson, Joseph H.; Woodruff, Prescott G.; Thornton, David J.; Rousseau, Karine; De la Garza, Maria M.; Moghaddam, Seyed J.; Karmouty-Quintana, Harry; Blackburn, Michael R.; Drouin, Scott M.; William Davis, C.; Terrell, Kristy A.; Grubb, Barbara R.; O’Neal, Wanda K.; Flores, Sonia C.; Cota-Gomez, Adela; Lozupone, Catherine A.; Donnelly, Jody M.; Watson, Alan M.; Hennessy, Corinne E.; Keith, Rebecca C.; Yang, Ivana V.; Barthel, Lea; Henson, Peter M.; Janssen, William J.; Schwartz, David A.; Boucher, Richard C.; Dickey, Burton F.; Evans, Christopher M.

    2014-01-01

    Respiratory surfaces are exposed to billions of particulates and pathogens daily. A protective mucus barrier traps and eliminates them via mucociliary clearance (MCC)1,2. However, excessive mucus contributes to transient respiratory infections and to the pathogenesis of numerous respiratory diseases1. MUC5AC and MUC5B are evolutionarily conserved genes that encode structurally related mucin glycoproteins, the principal macromolecules in airway mucus1,3. Genetic variants are linked to diverse lung diseases4-6, but specific roles for MUC5AC and MUC5B in MCC, and the lasting effects of their inhibition, are unknown. Here we show that Muc5b (but not Muc5ac) is required for MCC, for controlling infections in the airways and middle ear, and for maintaining immune homeostasis in the lungs. Muc5b deficiency caused materials to accumulate in upper and lower airways. This defect led to chronic infection by multiple bacterial species, including Staphylococcus aureus, and to inflammation that failed to resolve normally7. Apoptotic macrophages accumulated, phagocytosis was impaired, and IL-23 production was reduced inMuc5b−/− mice. By contrast, in Muc5b transgenic (Tg) mice, macrophage functions improved. Existing dogma defines mucous phenotypes in asthma and chronic obstructive pulmonary disease (COPD) as driven by increased MUC5AC, with MUC5B levels either unaffected or increased in expectorated sputum1,8. However, in many patients, MUC5B production at airway surfaces decreases by as much as 90%9-11. By distinguishing a specific role for Muc5b in MCC, and by determining its impact on bacterial infections and inflammation in mice, our results provide a refined framework for designing targeted therapies to control mucin secretion and restore MCC. PMID:24317696

  3. Airway and lung pathology due to mucosal surface dehydration in β-Epithelial Na+ Channel-overexpressing mice: role of TNFα and IL-4Rα signaling, influence of neonatal development, and limited efficacy of glucocorticoid treatment

    PubMed Central

    Livraghi, Alessandra; Grubb, Barbara R.; Hudson, Elizabeth J.; Wilkinson, Kristen J.; Sheehan, John K.; Mall, Marcus A.; O'Neal, Wanda K.; Boucher, Richard C.; Randell, Scott H.

    2009-01-01

    Overexpression of the epithelial Na+ channel β subunit (Scnn1b gene, βENaC protein) in transgenic (Tg) mouse airways dehydrates mucosal surfaces, producing mucus obstruction, inflammation, and neonatal mortality. Airway inflammation includes macrophage activation, neutrophil and eosinophil recruitment, and elevated KC, TNFα and chitinase levels. These changes recapitulate aspects of complex human obstructive airway diseases, but their molecular mechanisms are poorly understood. We used genetic and pharmacologic approaches to identify pathways relevant to the development of Scnn1b-Tg mouse lung pathology. Genetic deletion of tumor necrosis factor alpha (TNFα) or its receptor, TNFR1, had no measurable effect on the phenotype. Deletion of the interleukin-4 receptor alpha subunit (IL-4Rα) abolished transient mucous secretory cell (MuSC) abundance and eosinophilia normally observed in neonatal wild-type (WT) mice. Similarly, IL-4Rα deficiency decreased MuSC and eosinophils in neonatal Scnn1b-Tg mice, which correlated with improved neonatal survival. However, chronic lung pathology in adult Scnn1b-Tg mice was not affected by IL-4Rα status. Prednisolone treatment ablated eosinophilia and MuSC in adult Scnn1b-Tg mice, but did not decrease mucus plugging or neutrophilia. These studies demonstrate that: 1) normal neonatal mouse airway development entails an IL-4Rα-dependent, transient abundance of MuSC and eosinophils; 2) absence of IL-4Rα improved neonatal survival of Scnn1b-Tg mice, likely reflecting decreased formation of asphyxiating mucus plugs; and 3) in Scnn1b-Tg mice, neutrophilia, mucus obstruction, and airspace enlargement are IL-4Rα- and TNFα-independent, and only MuSC and eosinophilia are sensitive to glucocorticoids. Thus, manipulation of multiple pathways will likely be required to treat the complex pathogenesis caused by airway surface dehydration. PMID:19299736

  4. Computational model for the regulation of extracellular ATP and adenosine in airway epithelia.

    PubMed

    Garcia, Guilherme J M; Picher, Maryse; Zuo, Peiying; Okada, Seiko F; Lazarowski, Eduardo R; Button, Brian; Boucher, Richard C; Elston, Tim C

    2011-01-01

    Extracellular nucleotides are key components of the signaling network regulating airway clearance. They are released by the epithelium into the airway surface liquid (ASL) to stimulate cilia beating activity, mucus secretion and airway hydration. Understanding the factors affecting their availability for purinoceptor activation is an important step toward the development of new therapies for obstructive lung diseases. This chapter presents a mathematical model developed to gain predictive insights into the regulation of ASL nucleotide concentrations on human airway epithelia. The parameters were estimated from experimental data collected on polarized primary cultures of human nasal and bronchial epithelial cells. This model reproduces major experimental observations: (1) the independence of steady-state nucleotide concentrations on ASL height, (2) the impact of selective ectonucleotidase inhibitors on their steady-state ASL concentrations, (3) the changes in ASL composition caused by mechanical stress mimicking normal breathing, (4) and the differences in steady-state concentrations existing between nasal and bronchial epithelia. In addition, this model launched the study of nucleotide release into uncharted territories, which led to the discovery that airway epithelia release, not only ATP, but also ADP and AMP. This study shows that computational modeling, coupled to experimental validation, provides a powerful approach for the identification of key therapeutic targets for the improvement of airway clearance in obstructive respiratory diseases. PMID:21560044

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

    PubMed Central

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

    2013-01-01

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

  6. Sensitization of Upper Airway Mechanoreceptors as a New Pharmacologic Principle to Treat Obstructive Sleep Apnea: Investigations with AVE0118 in Anesthetized Pigs

    PubMed Central

    Wirth, Klaus J.; Steinmeyer, Klaus; Ruetten, Hartmut

    2013-01-01

    Study Objectives: Drug treatment for obstructive sleep apnea (OSA) is desirable because at least 30% of patients do not tolerate continuous positive airway pressure (CPAP) treatment. The negative pressure reflex (NPR) involving superficially located mechanoreceptors in the upper airway (UA) is an important mechanism for UA patency inhibitable by topical UA anesthesia (lidocaine). The NPR may serve as a target for pharmacological intervention for a topical treatment of OSA. The objective was to determine the effect of pharmacological augmentation of the NPR on UA collapsibility. Design: We developed a model of UA collapsibility in which application of negative pressures caused UA collapses in spontaneously breathing α-chloralose-urethane anesthetized pigs as indicated by characteristic tracheal pressure and air flow changes. Setting: N/A. Patients or Participants: N/A. Interventions: N/A. Measurements and Results: The potassium channel blocker AVE0118 administered topically to the UA in doses of 1, 3, and 10 mg per nostril sensitized the NPR, shifting the mechanoreceptor response threshold for the genioglossus muscle to more positive pressures (P < 0.001; n = 6 per group) and dose-dependently inhibited UA collapsibility. Ten mg of AVE0118 prevented UA collapses against negative pressures of -150 mbar (P < 0.01) for > 4 h in all pigs, while in control pigs the UA collapsed at -50 mbar or less negative pressures. The effect of AVE0118 was abolished by UA lidocaine anesthesia. Acute intravenous administration of naloxone or acetazolamide was ineffective; paroxetine and mirtazepine were weakly effective and fluoxetine was moderately effective in line with reported clinical efficacy. Conclusion: Topical administration of AVE0118 to the UA is a promising pharmacologic approach for the treatment of OSA. Citation: Wirth KJ; Steinmeyer K; Ruetten H. Sensitization of upper airway mechanoreceptors as a new pharmacologic principle to treat obstructive sleep apnea

  7. Impaired Mucus Detachment Disrupts Mucociliary Transport in a Piglet Model of Cystic Fibrosis

    PubMed Central

    Hoegger, Mark J.; Fischer, Anthony J.; McMenimen, James D.; Ostedgaard, Lynda S.; Tucker, Alex J.; Awadalla, Maged A.; Moninger, Thomas O.; Michalski, Andrew S.; Hoffman, Eric A.; Zabner, Joseph; Stoltz, David A.; Welsh, Michael J.

    2015-01-01

    Lung disease in people with cystic fibrosis (CF) is initiated by defective host defense that predisposes airways to bacterial infection. People with advanced CF exhibit deficits in mucociliary transport (MCT), a process that traps and propels bacteria out of lungs, but whether this occurs first or is secondary to airway remodeling has been unclear. To assess MCT, we tracked movement of radiodense microdisks in airways of newborn CF piglets. Cholinergic stimulation, which elicits mucus secretion, caused microdisks to become stuck. Impaired MCT was not due to periciliary liquid depletion; rather, CF submucosal glands secreted mucus strands that remained tethered to gland ducts and hindered MCT. Inhibiting anion secretion in non-CF airways replicated CF abnormalities. These findings identify impaired MCT as a primary defect, link CFTR loss in submucosal glands to failure of mucus detachment from glands, and suggest that submucosal glands and tethered mucus may be targets for early CF treatment. PMID:25124441

  8. Sex differences of continuous positive airway pressure treatment on flow-mediated dilation in patients with obstructive sleep apnea syndrome

    PubMed Central

    Kallianos, Anastasios; Panoutsopoulos, Athanasios; Mermigkis, Christoforos; Kostopoulos, Konstantinos; Papamichail, Chrysanthi; Kokkonouzis, Ioannis; Kostopoulos, Christoforos; Nikolopoulos, Ioannis; Papaiwannou, Antonis; Lampaki, Sofia; Organtzis, John; Pitsiou, Georgia; Zarogoulidis, Paul; Trakada, Georgia

    2015-01-01

    Introduction There is growing research evidence suggesting the presence of endothelial dysfunction and systemic inflammation in patients with obstructive sleep apnea syndrome (OSAS). Continuous positive airway pressure (CPAP) is the most effective method for treating OSAS; nonetheless, the effects of CPAP on the aforementioned pathophysiologic pathways as well as on the systemic disease that result or coexist with the OSAS remain elusive. Aim To assess the effect of 3-month CPAP therapy on endothelial-dependent dilation, plasma levels of inflammatory markers, blood pressure (BP), and glucose control on male and female patients with OSAS. Methods Our study group consisted of 40 (24 males and 16 females) patients with no prior history of cardiovascular disease, with an apnea–hypopnea index ≥15, who were assigned to receive CPAP treatment. Measurements of flow-mediated dilation (FMD), 24-hour ambulatory BP, and blood analysis were performed at baseline and 3 months after CPAP therapy. Results Baseline FMD values were negatively correlated with the apnea–hypopnea index (r=−0.55, P=0.001). After 3 months of CPAP, there was an increase in the FMD values (5.40%±2.91% vs 3.13%±3.15%, P<0.05) and a significant reduction in the patients’ 24-hour systolic BP (122.82±11.88 mmHg vs 130.24±16.75 mmHg, P<0.05), diastolic BP (75.44±9.14 mmHg vs 79.68±11.09 mmHg, P<0.05), and pulse pressure (47.38±9.77 mmHg vs 52.72±11.38 mmHg, P<0.05); daytime systolic BP (125.76±12.69 mmHg vs 132.55±17.00 mmHg, P<0.05) and diastolic BP (77.88±10.39 mmHg vs 82.25±11.01 mmHg, P<0.05); nighttime systolic BP (118.17±13.16 mmHg vs 126.22±17.42 mmHg, P<0.05) and pulse pressure (46.61±10.76 mmHg vs 52.66±11.86 mmHg, P<0.05); and C-reactive protein and HbA1c levels (0.40 [0.40–0.70] mg/L vs 0.60 [0.40–0.84] mg/L and 5.45%±0.70% vs 5.95%±1.08%, respectively; P<0.05). When divided by sex, only male patients produced similar statistically significant results, while female

  9. [Acute bacterial exacerbation of chronic obstructive pulmonary disease and biofilm].

    PubMed

    Legnani, Delfino

    2009-07-01

    The lower respiratory tract of patients affected by COPD is constantly colonized by pathogenic microrganisms such as H. influenzae, M. catarrhalis and S. pneumoniae. Role of bacterial colonization of big and small airways in patients affected by COPD is still unclear but it is likely to play a role in directly or indirectly maintaining the vicious circle of infection/inflammation. Colonizer pathogens are capable to stimulate mucus production, to alter the ciliary function by inducing dyskinesia and stasis; in addition, they represent a strong stimulus for neutrophils to come in the airways, which release elastase that, in turn, inhibit the mucus-ciliary function. The same pathogens are responsible for epithelial damage and chronic inflammation, by releasing neutrophilic elastase, leading to the damage progression and obstruction. Recent studies have also shown that infection sustained by H. influenzae is not limited to bronchial mucosa, i.e. surface epithelial cells, but that the pathogen is capable to penetrate cells, so spreading the infection in sub-epithelial cellular layers. In addition, the ability to produce biofilm is another possible defence mechanism which allows them to grow and colonise. Such a mechanism could in part explain the lack of response to antimicrobials and contribute to stimulation of parenchymal inflammatory response, the cause of pathological-anatomic damage which occurs in COPD. The impossibility to eradicate chronic infection and bacterial exacerbations of COPD are likely the elements that promt and worsen obstruction, so determining the disease's progression. PMID:19696555

  10. Removal of endotracheal tube obstruction with a secretion clearance device.

    PubMed

    Mietto, Cristina; Foley, Kevin; Salerno, Lindsay; Oleksak, Jenna; Pinciroli, Riccardo; Goverman, Jeremy; Berra, Lorenzo

    2014-09-01

    Accumulation of secretions may suddenly occlude an endotracheal tube (ETT), requiring immediate medical attention. The endOclear catheter (Endoclear LLC, Petoskey, Michigan) is a novel device designed to clear mucus and debris from an ETT and restore luminal patency. We present 3 subsequent cases of life-threatening partial ETT occlusions recorded over a period of 6 months at Massachusetts General Hospital. After conventional methods (standard tracheal suctioning and bronchoscopy) failed, the endOclear was used, with successful restoration of the airways in all 3 cases. The respiratory conditions rapidly improved, and all 3 patients tolerated the ETT-cleaning maneuver. These results show that such a device is safe and easy to use during an emergency airway situation for efficient and rapid removal of secretions from obstructed ETTs by respiratory therapists. PMID:24368863

  11. Differences in perceptions of the diagnosis and treatment of obstructive sleep apnea and continuous positive airway pressure therapy among adherers and nonadherers.

    PubMed

    Sawyer, Amy M; Deatrick, Janet A; Kuna, Samuel T; Weaver, Terri E

    2010-07-01

    Obstructive sleep apnea (OSA) patients' consistent use of continuous positive airway pressure (CPAP) therapy is critical to realizing improved functional outcomes and reducing untoward health risks associated with OSA. We conducted a mixed methods, concurrent, nested study to explore OSA patients' beliefs and perceptions of the diagnosis and CPAP treatment that differentiate adherent from nonadherent patients prior to and after the first week of treatment, when the pattern of CPAP use is established. Guided by social cognitive theory, themes were derived from 30 interviews conducted postdiagnosis and after 1 week of CPAP use. Directed content analysis, followed by categorization of participants as adherent/nonadherent from objectively measured CPAP use, preceded across-case analysis among 15 participants with severe OSA. Beliefs and perceptions that differed between adherers and nonadherers included OSA risk perception, symptom recognition, self-efficacy, outcome expectations, treatment goals, and treatment facilitators/ barriers. Our findings suggest opportunities for developing and testing tailored interventions to promote CPAP use. PMID:20354236

  12. Monitoring Progress and Adherence with Positive Airway Pressure Therapy for Obstructive Sleep Apnea: The Roles of Telemedicine and Mobile Health Applications.

    PubMed

    Hwang, Dennis

    2016-06-01

    Technology is changing the way health care is delivered and how patients are approaching their own health. Given the challenge within sleep medicine of optimizing adherence to continuous positive airway pressure (CPAP) therapy in patients with obstructive sleep apnea (OSA), implementation of telemedicine-based mechanisms is a critical component toward developing a comprehensive and cost-effective solution for OSA management. Key elements include the use of electronic messaging, remote monitoring, automated care mechanisms, and patient self-management platforms. Current practical sleep-related telemedicine platforms include Web-based educational programs, automated CPAP follow-up platforms that promote self-management, and peer-based patient-driven Internet support forums. PMID:27236054

  13. Efficacy of Bilevel-auto Treatment in Patients with Obstructive Sleep Apnea Not Responsive to or Intolerant of Continuous Positive Airway Pressure Ventilation

    PubMed Central

    Carlucci, Annalisa; Ceriana, Piero; Mancini, Marco; Cirio, Serena; Pierucci, Paola; D'Artavilla Lupo, Nadia; Gadaleta, Felice; Morrone, Elisa; Fanfulla, Francesco

    2015-01-01

    Background: Ventilation with continuous positive airway pressure (CPAP) is the gold standard therapy for obstructive sleep apnea (OSA). However, it was recently suggested that a novel mode of ventilation, Bilevel-auto, could be equally effective in treating patients unable to tolerate CPAP. The aim of this study was to investigate the ability of Bilevel-auto to treat OSA patients whose nocturnal ventilatory disturbances are not completely corrected by CPAP. Methods: We enrolled 66 consecutive OSA patients, not responsive to (group A) or intolerant of (group B) CPAP treatment, after a full night of manual CPAP titration in a laboratory. Full polysomnography data and daytime sleepiness score were compared for each group in the three different conditions: basal, during CPAP, and during Bilevel-auto. Results: The apnea-hypopnea index decreased significantly during CPAP in both groups; however, in the group A, there was a further significant improvement during Bilevel-auto. The same trend was observed for oxygenation indices, while the distribution and the efficiency of sleep did not differ following the switch from CPAP to Bilevel-auto. Conclusions: This study confirmed the role of Bilevel-auto as an effective therapeutic alternative to CPAP in patients intolerant of this latter mode of ventilation. Moreover, extending the use of Bilevel-auto to those OSA patients not responsive to CPAP, we showed a significantly better correction of nocturnal respiratory disturbances. Citation: Carlucci A, Ceriana P, Mancini M, Cirio S, Pierucci P, D'Artavilla Lupo N, Gadaleta F, Morrone E, Fanfulla F. Efficacy of Bilevel-auto treatment in patients with obstructive sleep apnea not responsive to or intolerant of continuous positive airway pressure ventilation. J Clin Sleep Med 2015;11(9):981–985. PMID:25902825

  14. Continuous Positive Airway Pressure Reduces Risk of Motor Vehicle Crash among Drivers with Obstructive Sleep Apnea: Systematic Review and Meta-analysis

    PubMed Central

    Tregear, Stephen; Reston, James; Schoelles, Karen; Phillips, Barbara

    2010-01-01

    Context: Obstructive sleep apnea (OSA) is associated with an increased risk of motor vehicle crash. Objective: We performed a systematic review of the literature concerning the impact of continuous positive airway pressure (CPAP) treatment on motor vehicle crash risk among drivers with OSA. The primary objective was to determine whether CPAP use could reduce the risk of motor vehicle crash among drivers with OSA. A secondary objective involved determining the time on treatment required for CPAP to improve driver safety. Data Sources: We searched seven electronic databases (MEDLINE, PubMed (PreMEDLINE), EMBASE, PsycINFO, CINAHL, TRIS, and the Cochrane library) and the reference lists of all obtained articles. Study Selection: We included studies (before-after, case-control, or cohort) that addressed the stated objectives. We evaluated the quality of each study and the interplay between the quality, quantity, robustness, and consistency of the evidence. We also tested for publication bias. Data Extraction: Data were extracted by two independent analysts. When appropriate, data were combined in a fixed or random effects meta-analysis. Results: A meta-analysis of 9 observational studies examining crash risk of drivers with OSA pre- vs. post-CPAP found a significant risk reduction following treatment (risk ratio = 0.278, 95% CI: 0.22 to 0.35; P < 0.001). Although crash data are not available to assess the time course of change, daytime sleepiness improves significantly following a single night of treatment, and simulated driving performance improves significantly within 2 to 7 days of CPAP treatment. Conclusions: Observational studies indicate that CPAP reduces motor vehicle crash risk among drivers with OSA. Citation: Tregear S; Reston J; Schoelles K; Phillips B. Continuous positive airway pressure reduces risk of motor vehicle crash among drivers with obstructive sleep apnea. SLEEP 2010;33(10):1373-1380. PMID:21061860

  15. Effects of Armodafinil on Simulated Driving and Self-Report Measures in Obstructive Sleep Apnea Patients prior to Treatment with Continuous Positive Airway Pressure

    PubMed Central

    Kay, Gary G.; Feldman, Neil

    2013-01-01

    Study Objectives: Obstructive sleep apnea (OSA) has been associated with an increased risk of motor vehicle crashes. This driving risk can be reduced (≥ 50%) by treatment with continuous positive airway pressure (CPAP). However residual excessive daytime sleepiness (EDS) can persist for some patients who regularly use CPAP. The current study was designed to assess the effect of armodafinil on simulated driving performance and subsequent CPAP treatment compliance in newly diagnosed OSA patients with EDS during a 2-week “waiting period” prior to initiation of CPAP. Methods: Sixty-nine newly diagnosed OSA patients, awaiting CPAP therapy, were randomized (1:1) to placebo or armodafinil (150 mg/day) treatment. Simulated driving tests and self-report measures were completed at baseline, after 2 weeks of drug treatment, and following 6 weeks of CPAP treatment. CPAP compliance was evaluated at the end of 6 weeks of CPAP. Results: Compared to placebo, armodafinil improved simulated driving safety performance in OSA patients awaiting CPAP therapy (p = 0.03). Improvement was seen in lane position deviation (p = 0.002) and number of lane excursions (p = 0.02). Improvement was also observed on measures of sleepiness using the Epworth Sleepiness Scale (ESS) and sleep related quality of life. Following 6 weeks of CPAP, there was also significant improvement observed on multiple measures of simulated driving performance. CPAP compliance did not differ between armodafinil-treated and placebo-treated patients (p = 0.80). Conclusions: Armodafinil was found to improve simulated driving performance in OSA patients with EDS prior to initiation of CPAP. Treatment with armodafinil showed no effect on subsequent CPAP compliance. Citation: Kay GG; Feldman N. Effects of armodafinil on simulated driving and self-report measures in obstructive sleep apnea patients prior to treatment with continuous positive airway pressure. J Clin Sleep Med 2013;9(5):445-454. PMID:23674935

  16. Multi-scale computational models of the airways to unravel the pathophysiological mechanisms in asthma and chronic obstructive pulmonary disease (AirPROM)

    PubMed Central

    Burrowes, K. S.; De Backer, J.; Smallwood, R.; Sterk, P. J.; Gut, I.; Wirix-Speetjens, R.; Siddiqui, S.; Owers-Bradley, J.; Wild, J.; Maier, D.; Brightling, C.

    2013-01-01

    The respiratory system comprises several scales of biological complexity: the genes, cells and tissues that work in concert to generate resultant function. Malfunctions of the structure or function of components at any spatial scale can result in diseases, to the detriment of gas exchange, right heart function and patient quality of life. Vast amounts of data emerge from studies across each of the biological scales; however, the question remains: how can we integrate and interpret these data in a meaningful way? Respiratory disease presents a huge health and economic burden, with the diseases asthma and chronic obstructive pulmonary disease (COPD) affecting over 500 million people worldwide. Current therapies are inadequate owing to our incomplete understanding of the disease pathophysiology and our lack of recognition of the enormous disease heterogeneity: we need to characterize this heterogeneity on a patient-specific basis to advance healthcare. In an effort to achieve this goal, the AirPROM consortium (Airway disease Predicting Outcomes through patient-specific computational Modelling) brings together a multi-disciplinary team and a wealth of clinical data. Together we are developing an integrated multi-scale model of the airways in order to unravel the complex pathophysiological mechanisms occurring in the diseases asthma and COPD. PMID:24427517

  17. Cerebral hemodynamics in patients with obstructive sleep apnea syndrome monitored with near-infrared spectroscopy (NIRS) during positive airways pressure (CPAP) therapy: a pilot study

    NASA Astrophysics Data System (ADS)

    Zhang, Zhongxing; Schneider, Maja; Laures, Marco; Fritschi, Ursula; Lehner, Isabella; Qi, Ming; Khatami, Ramin

    2014-03-01

    In obstructive sleep apnea syndrome (OSA) the periodic reduction or cessation of breathing due to narrowing or occlusion of the upper airway during sleep leads to daytime symptoms and increased cardiovascular risk, including stroke. The higher risk of stroke is related to the impairment in cerebral vascular autoregulation. Continuous positive airways pressure (CPAP) therapy at night is the most effective treatment for OSA. However, there is no suitable bedside monitoring method evaluating the treatment efficacy of CPAP therapy, especially to monitor the recovery of cerebral hemodynamics. NIRS is ideally suited for non-invasive monitoring the cerebral hemodynamics during sleep. In this study, we will for first time assess dynamic changes of cerebral hemodynamics during nocturnal CPAP therapy in 3 patients with OSA using NIRS. We found periodic oscillations in HbO2, HHb, tissue oxygenation index (TOI) and blood volume associated with periodic apnea events without CPAP in all OSA patients. These oscillations were gradually attenuated and finally eliminated with the stepwise increments of CPAP pressures. The oscillations were totally eliminated in blood volume earlier than in other hemodynamic parameters. These results suggested that 1) the cerebral hemodynamic oscillations induced by OSA events can effectively be attenuated by CPAP therapy, and 2) blood flow and blood volume recovered first during CPAP therapy, followed by the recovery of oxygen consumption. Our study suggested that NIRS is a useful tool to evaluate the efficacy of CPAP therapy in patients with OSA bedside and in real time.

  18. The novel compound Sul-121 inhibits airway inflammation and hyperresponsiveness in experimental models of chronic obstructive pulmonary disease

    PubMed Central

    Han, Bing; Poppinga, Wilfred J.; Zuo, Haoxiao; Zuidhof, Annet B.; Bos, I. Sophie T.; Smit, Marieke; Vogelaar, Pieter; Krenning, Guido; Henning, Robert H.; Maarsingh, Harm; Halayko, Andrew J.; van Vliet, Bernard; Stienstra, Stef; Graaf, Adrianus Cornelis van der; Meurs, Herman; Schmidt, Martina

    2016-01-01

    COPD is characterized by persistent airflow limitation, neutrophilia and oxidative stress from endogenous and exogenous insults. Current COPD therapy involving anticholinergics, β2-adrenoceptor agonists and/or corticosteroids, do not specifically target oxidative stress, nor do they reduce chronic pulmonary inflammation and disease progression in all patients. Here, we explore the effects of Sul-121, a novel compound with anti-oxidative capacity, on hyperresponsiveness (AHR) and inflammation in experimental models of COPD. Using a guinea pig model of lipopolysaccharide (LPS)-induced neutrophilia, we demonstrated that Sul-121 inhalation dose-dependently prevented LPS-induced airway neutrophilia (up to ~60%) and AHR (up to ~90%). Non-cartilaginous airways neutrophilia was inversely correlated with blood H2S, and LPS-induced attenuation of blood H2S (~60%) was prevented by Sul-121. Concomitantly, Sul-121 prevented LPS-induced production of the oxidative stress marker, malondialdehyde by ~80%. In immortalized human airway smooth muscle (ASM) cells, Sul-121 dose-dependently prevented cigarette smoke extract-induced IL-8 release parallel with inhibition of nuclear translocation of the NF-κB subunit, p65 (each ~90%). Sul-121 also diminished cellular reactive oxygen species production in ASM cells, and inhibited nuclear translocation of the anti-oxidative response regulator, Nrf2. Our data show that Sul-121 effectively inhibits airway inflammation and AHR in experimental COPD models, prospectively through inhibition of oxidative stress. PMID:27229886

  19. The novel compound Sul-121 inhibits airway inflammation and hyperresponsiveness in experimental models of chronic obstructive pulmonary disease.

    PubMed

    Han, Bing; Poppinga, Wilfred J; Zuo, Haoxiao; Zuidhof, Annet B; Bos, I Sophie T; Smit, Marieke; Vogelaar, Pieter; Krenning, Guido; Henning, Robert H; Maarsingh, Harm; Halayko, Andrew J; van Vliet, Bernard; Stienstra, Stef; Graaf, Adrianus Cornelis van der; Meurs, Herman; Schmidt, Martina

    2016-01-01

    COPD is characterized by persistent airflow limitation, neutrophilia and oxidative stress from endogenous and exogenous insults. Current COPD therapy involving anticholinergics, β2-adrenoceptor agonists and/or corticosteroids, do not specifically target oxidative stress, nor do they reduce chronic pulmonary inflammation and disease progression in all patients. Here, we explore the effects of Sul-121, a novel compound with anti-oxidative capacity, on hyperresponsiveness (AHR) and inflammation in experimental models of COPD. Using a guinea pig model of lipopolysaccharide (LPS)-induced neutrophilia, we demonstrated that Sul-121 inhalation dose-dependently prevented LPS-induced airway neutrophilia (up to ~60%) and AHR (up to ~90%). Non-cartilaginous airways neutrophilia was inversely correlated with blood H2S, and LPS-induced attenuation of blood H2S (~60%) was prevented by Sul-121. Concomitantly, Sul-121 prevented LPS-induced production of the oxidative stress marker, malondialdehyde by ~80%. In immortalized human airway smooth muscle (ASM) cells, Sul-121 dose-dependently prevented cigarette smoke extract-induced IL-8 release parallel with inhibition of nuclear translocation of the NF-κB subunit, p65 (each ~90%). Sul-121 also diminished cellular reactive oxygen species production in ASM cells, and inhibited nuclear translocation of the anti-oxidative response regulator, Nrf2. Our data show that Sul-121 effectively inhibits airway inflammation and AHR in experimental COPD models, prospectively through inhibition of oxidative stress. PMID:27229886

  20. Impact of the type of mask on the effectiveness of and adherence to continuous positive airway pressure treatment for obstructive sleep apnea*

    PubMed Central

    de Andrade, Rafaela Garcia Santos; Piccin, Vivien Schmeling; Nascimento, Juliana Araújo; Viana, Fernanda Madeiro Leite; Genta, Pedro Rodrigues; Lorenzi-Filho, Geraldo

    2014-01-01

    Continuous positive airway pressure (CPAP) is the gold standard for the treatment of obstructive sleep apnea (OSA). Although CPAP was originally applied with a nasal mask, various interfaces are currently available. This study reviews theoretical concepts and questions the premise that all types of interfaces produce similar results. We revised the evidence in the literature about the impact that the type of CPAP interface has on the effectiveness of and adherence to OSA treatment. We searched the PubMed database using the search terms "CPAP", "mask", and "obstructive sleep apnea". Although we identified 91 studies, only 12 described the impact of the type of CPAP interface on treatment effectiveness (n = 6) or adherence (n = 6). Despite conflicting results, we found no consistent evidence that nasal pillows and oral masks alter OSA treatment effectiveness or adherence. In contrast, most studies showed that oronasal masks are less effective and are more often associated with lower adherence and higher CPAP abandonment than are nasal masks. We concluded that oronasal masks can compromise CPAP OSA treatment adherence and effectiveness. Further studies are needed in order to understand the exact mechanisms involved in this effect. PMID:25610507

  1. Pilot study investigating the ability of an herbal composite to alleviate clinical signs of respiratory dysfunction in horses with recurrent airway obstruction

    PubMed Central

    Pearson, Wendy; Charch, Armen; Brewer, Dyanne; Clarke, Andrew F.

    2007-01-01

    Recurrent airway obstruction (RAO), known previously as chronic obstructive pulmonary disease (COPD), is a debilitating respiratory condition that significantly contributes to lost training days and illness in racehorses. Herbs are becoming increasingly popular for the prophylaxis or treatment of the clinical signs of RAO despite a paucity of research on efficacy and safety. We evaluated the ability of an herbal composite containing garlic, white horehound, boneset, aniseed, fennel, licorice, thyme, and hyssop to reduce the clinical signs of RAO, hypothesizing that the product would safely reduce signs and would improve the inflammatory cell profile within the lungs. The composite was fed to 6 horses with symptomatic RAO for 21 d in a crossover manner. Ventigraphs were used to record respiratory rate and intrapleural pressure; the proportion of inflammatory cells in fluid aspirated from the trachea was determined. Blood biochemical and hematologic screening was conducted to identify possible adverse effects. Treatment with the composite did not result in statistically significant changes in any of the parameters evaluated. A trend to a decrease in respiratory rate (P = 0.1) and an increase in the proportion of macrophages (P = 0.1) was observed in the horses receiving the herbal composite compared with placebo. These data indicate a potential for the herbal composite to safely reduce the elevated respiratory rate in horses with RAO. Future research with a greater number of horses is warranted to further characterize the effect of this product on horses with RAO. PMID:17479778

  2. Web-Based Access to Positive Airway Pressure Usage with or without an Initial Financial Incentive Improves Treatment Use in Patients with Obstructive Sleep Apnea

    PubMed Central

    Kuna, Samuel T.; Shuttleworth, David; Chi, Luqi; Schutte-Rodin, Sharon; Friedman, Eliot; Guo, Hengyi; Dhand, Sandeep; Yang, Lin; Zhu, Jingsan; Bellamy, Scarlett L.; Volpp, Kevin G.; Asch, David A.

    2015-01-01

    Study Objectives: We tested whether providing adults with obstructive sleep apnea (OSA) with daily Web-based access to their positive airway pressure (PAP) usage over 3 mo with or without a financial incentive in the first week improves adherence and functional outcomes. Setting: Academic- and community-based sleep centers. Participants: One hundred thirty-eight adults with newly diagnosed OSA starting PAP treatment. Interventions: Participants were randomized to: usual care, usual care with access to PAP usage, or usual care with access to PAP usage and a financial incentive. PAP data were transmitted daily by wireless modem from the participants' PAP unit to a website where hours of usage were displayed. Participants in the financial incentive group could earn up to $30/day in the first week for objective PAP use ≥ 4 h/day. Measurements and Results: Mean hours of daily PAP use in the two groups with access to PAP usage data did not differ from each other but was significantly greater than that in the usual care group in the first week and over 3 mo (P < 0.0001). Average daily use (mean ± standard deviation) during the first week of PAP intervention was 4.7 ± 3.3 h in the usual care group, and 5.9 ± 2.5 h and 6.3 ± 2.5 h in the Web access groups with and without financial incentive respectively. Adherence over the 3-mo intervention decreased at a relatively constant rate in all three groups. Functional Outcomes of Sleep Questionnaire change scores at 3 mo improved within each group (P < 0.0001) but change scores of the two groups with Web access to PAP data were not different than those in the control group (P > 0.124). Conclusions: Positive airway pressure adherence is significantly improved by giving patients Web access to information about their use of the treatment. Inclusion of a financial incentive in the first week had no additive effect in improving adherence. Citation: Kuna ST, Shuttleworth D, Chi L, Schutte-Rodin S, Friedman E, Guo H, Dhand S, Yang

  3. Structure and function of airway surface layer of the human lungs & mobility of probe particles in complex fluids

    NASA Astrophysics Data System (ADS)

    Cai, Liheng

    Numerous infectious particles such as bacteria and pathogens are deposited on the airway surface of the human lungs during our daily breathing. To avoid infection the lung has evolved to develop a smart and powerful defense system called mucociliary clearance. The airway surface layer is a critical component of this mucus clearance system, which consists of two parts: (1) a mucus layer, that traps inhaled particles and transports them out of the lung by cilia-generated flow; and (2) a periciliary layer, that provides a favorable environment for ciliary beating and cell surface lubrication. For 75 years, it has been dogma that a single gel-like mucus layer, which is composed of secreted mucin glycoproteins, is transported over a "watery" periciliary layer. This one-gel model, however, does not explain fundamental features of the normal system, e.g. formation of a distinct mucus layer, nor accurately predict how the mucus clearance system fails in disease. In the first part of this thesis we propose a novel "Gel-on-Brush" model with a mucus layer (the "gel") and a "brush-like" periciliary layer, composed of mucins tethered to the luminal of airway surface, and supporting data accurately describes both the biophysical and cell biological bases for normal mucus clearance and its failure in disease. Our "Gel-on-Brush" model describes for the first time how and why mucus is efficiently cleared in health and unifies the pathogenesis of major human diseases, including cystic fibrosis and chronic obstructive pulmonary disease. It is expected that this "Gel-on-Brush" model of airway surface layer opens new directions for treatments of airway diseases. A dilemma regarding the function of mucus is that, although mucus traps any inhaled harmful particulates, it also poses a long-time problem for drug delivery: mobility of cargos carrying pharmaceutical agents is slowed down in mucus. The second part of this thesis aims to answer the question: can we theoretically understand the

  4. Lung Gene Therapy with Highly Compacted DNA Nanoparticles that Overcome the Mucus Barrier

    PubMed Central

    Suk, Jung Soo; Kim, Anthony J.; Trehan, Kanika; Schneider, Craig S.; Cebotaru, Liudmila; Woodward, Owen M.; Boylan, Nicholas J.; Boyle, Michael P.; Lai, Samuel K.; Guggino, William B.; Hanes, Justin

    2014-01-01

    Inhaled gene carriers must penetrate the highly viscoelastic and adhesive mucus barrier in the airway in order to overcome rapid mucociliary clearance and reach the underlying epithelium; however, even the most widely used viral gene carriers are unable to efficiently do so. We developed two polymeric gene carriers that compact plasmid DNA into small and highly stable nanoparticles with dense polyethylene glycol (PEG) surface coatings. These highly compacted, densely PEG-coated DNA nanoparticles rapidly penetrate human cystic fibrosis (CF) mucus ex vivo and mouse airway mucus ex situ. Intranasal administration of the mucus penetrating DNA nanoparticles greatly enhanced particle distribution, retention and gene transfer in the mouse lung airways compared to conventional gene carriers. Successful delivery of a full-length plasmid encoding the cystic fibrosis transmembrane conductance regulator protein was achieved in mouse lungs and airway cells, including a primary culture of mucus-covered human airway epithelium grown at air-liquid interface, without causing acute inflammation or toxicity. Highly compacted mucus penetrating DNA nanoparticles hold promise for lung gene therapy. PMID:24440664

  5. Lung gene therapy with highly compacted DNA nanoparticles that overcome the mucus barrier.

    PubMed

    Suk, Jung Soo; Kim, Anthony J; Trehan, Kanika; Schneider, Craig S; Cebotaru, Liudmila; Woodward, Owen M; Boylan, Nicholas J; Boyle, Michael P; Lai, Samuel K; Guggino, William B; Hanes, Justin

    2014-03-28

    Inhaled gene carriers must penetrate the highly viscoelastic and adhesive mucus barrier in the airway in order to overcome rapid mucociliary clearance and reach the underlying epithelium; however, even the most widely used viral gene carriers are unable to efficiently do so. We developed two polymeric gene carriers that compact plasmid DNA into small and highly stable nanoparticles with dense polyethylene glycol (PEG) surface coatings. These highly compacted, densely PEG-coated DNA nanoparticles rapidly penetrate human cystic fibrosis (CF) mucus ex vivo and mouse airway mucus ex situ. Intranasal administration of the mucus penetrating DNA nanoparticles greatly enhanced particle distribution, retention and gene transfer in the mouse lung airways compared to conventional gene carriers. Successful delivery of a full-length plasmid encoding the cystic fibrosis transmembrane conductance regulator protein was achieved in the mouse lungs and airway cells, including a primary culture of mucus-covered human airway epithelium grown at air-liquid interface, without causing acute inflammation or toxicity. Highly compacted mucus penetrating DNA nanoparticles hold promise for lung gene therapy. PMID:24440664

  6. Brachycephalic airway syndrome: management.

    PubMed

    Lodato, Dena L; Hedlund, Cheryl S

    2012-08-01

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

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

    PubMed Central

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

    2015-01-01

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

  8. Continuous Positive Airway Pressure Therapy for Obstructive Sleep Apnea: Maximizing Adherence Including Using Novel Information Technology-based Systems.

    PubMed

    Hevener, Bretton; Hevener, William

    2016-09-01

    Sleep apnea is a form of sleep-disordered breathing that is associated with an increase in disease comorbidities, mortality risks, health care costs, and traffic accidents. Sleep apnea is most commonly treated with positive airway pressure (PAP). PAP can be difficult for patients to tolerate. This leads to initial and long-term noncompliance. Most insurance companies require compliance with PAP treatment to cover ongoing reimbursements for the device and related disposable supplies. Therefore, there are both clinical and financial incentives to a sleep apneic patient's compliance with PAP therapy. PMID:27542878

  9. Impaired mucus detachment disrupts mucociliary transport in a piglet model of cystic fibrosis.

    PubMed

    Hoegger, Mark J; Fischer, Anthony J; McMenimen, James D; Ostedgaard, Lynda S; Tucker, Alex J; Awadalla, Maged A; Moninger, Thomas O; Michalski, Andrew S; Hoffman, Eric A; Zabner, Joseph; Stoltz, David A; Welsh, Michael J

    2014-08-15

    Lung disease in people with cystic fibrosis (CF) is initiated by defective host defense that predisposes airways to bacterial infection. Advanced CF is characterized by a deficit in mucociliary transport (MCT), a process that traps and propels bacteria out of the lungs, but whether this deficit occurs first or is secondary to airway remodeling has been unclear. To assess MCT, we tracked movement of radiodense microdisks in airways of newborn piglets with CF. Cholinergic stimulation, which elicits mucus secretion, substantially reduced microdisk movement. Impaired MCT was not due to periciliary liquid depletion; rather, CF submucosal glands secreted mucus strands that remained tethered to gland ducts. Inhibiting anion secretion in non-CF airways replicated CF abnormalities. Thus, impaired MCT is a primary defect in CF, suggesting that submucosal glands and tethered mucus may be targets for early CF treatment. PMID:25124441

  10. Effect of Positive Airway Pressure Therapy on Body Mass Index in Obese Patients With Obstructive Sleep Apnea Syndrome: A Prospective Study.

    PubMed

    Rishi, Muhammad Adeel; Copur, Ahmet Sinan; Nadeem, Rashid; Fulambarker, Ashok

    2016-01-01

    Because obesity is a common cause of obstructive sleep apnea syndrome (OSAS), weight loss can be an effective treatment. OSAS also may cause weight gain in some patients. Effective treatment of sleep apnea may facilitate weight loss in obese patients. We hypothesize that positive airway pressure (PAP) therapy is associated with weight loss in obese patients with OSAS. This was a single-center observational prospective cohort study. Forty-five patients were diagnosed with OSAS after polysomnographic analysis in sleep laboratory and underwent continuous positive airway pressure titration. Patients were followed for 3 months in terms of change in body mass index (BMI) and compliance with PAP therapy. Of the 45 patients recruited, 3 patients were eliminated because of miss recruitment. Nine patients had incomplete data, and the rest (n = 33) were included for analysis. The mean age was 54.9 ± 16.9 years (mean ± SD), 93.9% were male, and 90.9% were whites. Mean apnea-hypopnea index was 36.3 ± 28.17 events per hour. Mean BMI before treatment was 34.7 ± 3.9 kg/m. Fifteen patients (45.5%) were compliant with therapy of OSAS with PAP. There was no difference in age, gender, neck circumference, BMI, and apnea-hypopnea index of patients compliant to therapy when compared with those who were not. There was a significant decrease in BMI in patients compliant with PAP therapy compared with noncompliant patients (-1.2 ± 0.7 vs. 0.3 ± 0.9 kg/m, P ≤ 0.001). PAP therapy may cause significant loss of weight within 3 months in obese patients with OSAS. Further study is needed to elucidate the physiological basis of this change. PMID:25563675

  11. Bilateral Mandibular Distraction Osteogenesis in the Neonate with Pierre Robin Sequence and Airway Obstruction: A Primary Option

    PubMed Central

    Zenha, Horácio; Azevedo, Luis; Rios, Leonor; Pereira, Alberto; Pinto, Armindo; Barroso, Maria Luz; Costa, Horácio

    2012-01-01

    Children with craniofacial abnormalities associated with retromicrognathia and glossoptosis often have compromised upper airway flow. In severe cases, emergency intubation is necessary immediately after birth, and tracheostomy is advocated to manage the airway in the neonatal period and to allow for feeding. Early intervention with bilateral mandibular osteogenesis avoids the need for tracheostomy, along with its complications, and it targets the primary etiologic factor of the problem—the anomalous anatomy of the mandible. We report two neonates with severe Pierre Robin sequence managed with bilateral mandibular distraction osteogenesis on day 9 and day 11 of life. The surgical techniques and distraction and consolidation periods were similar apart from the distraction devices used. The procedures were successful with early extubation (day 5 and day 7), oral feeding tolerance (day 11 and day 13) and hospital discharge (day 19 and day 18). Total mandibular distraction was 19 mm and 23.45 mm, respectively. No major complications were reported. Medium to long-term results were good. Bilateral mandibular distraction osteogenesis in the neonate is a safe and accurate procedure and is the primary option in cases of selected severe Pierre Robin sequence. PMID:23450076

  12. Effects of Continuous Positive Airway Pressure on Neurocognitive Function in Obstructive Sleep Apnea Patients: The Apnea Positive Pressure Long-term Efficacy Study (APPLES)

    PubMed Central

    Kushida, Clete A.; Nichols, Deborah A.; Holmes, Tyson H.; Quan, Stuart F.; Walsh, James K.; Gottlieb, Daniel J.; Simon, Richard D.; Guilleminault, Christian; White, David P.; Goodwin, James L.; Schweitzer, Paula K.; Leary, Eileen B.; Hyde, Pamela R.; Hirshkowitz, Max; Green, Sylvan; McEvoy, Linda K.; Chan, Cynthia; Gevins, Alan; Kay, Gary G.; Bloch, Daniel A.; Crabtree, Tami; Dement, William C.

    2012-01-01

    Study Objective: To determine the neurocognitive effects of continuous positive airway pressure (CPAP) therapy on patients with obstructive sleep apnea (OSA). Design, Setting, and Participants: The Apnea Positive Pressure Long-term Efficacy Study (APPLES) was a 6-month, randomized, double-blind, 2-arm, sham-controlled, multicenter trial conducted at 5 U.S. university, hospital, or private practices. Of 1,516 participants enrolled, 1,105 were randomized, and 1,098 participants diagnosed with OSA contributed to the analysis of the primary outcome measures. Intervention: Active or sham CPAP Measurements: Three neurocognitive variables, each representing a neurocognitive domain: Pathfinder Number Test-Total Time (attention and psychomotor function [A/P]), Buschke Selective Reminding Test-Sum Recall (learning and memory [L/M]), and Sustained Working Memory Test-Overall Mid-Day Score (executive and frontal-lobe function [E/F]) Results: The primary neurocognitive analyses showed a difference between groups for only the E/F variable at the 2 month CPAP visit, but no difference at the 6 month CPAP visit or for the A/P or L/M variables at either the 2 or 6 month visits. When stratified by measures of OSA severity (AHI or oxygen saturation parameters), the primary E/F variable and one secondary E/F neurocognitive variable revealed transient differences between study arms for those with the most severe OSA. Participants in the active CPAP group had a significantly greater ability to remain awake whether measured subjectively by the Epworth Sleepiness Scale or objectively by the maintenance of wakefulness test. Conclusions: CPAP treatment improved both subjectively and objectively measured sleepiness, especially in individuals with severe OSA (AHI > 30). CPAP use resulted in mild, transient improvement in the most sensitive measures of executive and frontal-lobe function for those with severe disease, which suggests the existence of a complex OSA-neurocognitive relationship

  13. Long-term effects of acupuncture treatment on airway smooth muscle in a rat model of smoke-induced chronic obstructive pulmonary disease

    PubMed Central

    Li, Jia; Wu, Song; Tang, Hongtu; Huang, Wei; Wang, Lushan; Zhou, Huanjiao; Zhou, Miao; Wang, Hua; Li, Jing

    2016-01-01

    Background Chronic obstructive pulmonary disease (COPD) is one of the most common lung diseases. It is a chronic inflammatory process characterised by airway obstruction and progressive lung inflammation, associated with difficulty breathing and insensitivity to corticosteroid therapy. Although there is some preliminary evidence to suggest a beneficial effect of acupuncture on COPD, its mechanism of action has not been investigated. Our aim was to examine the anti-inflammatory effects of acupuncture in a rat model of COPD induced by exposure to cigarette smoke (CS). Methods Sixty Sprague–Dawley rats were exposed to the smoke of 15 cigarettes for 1 h/day, 6 days/week for 3 months to induce COPD and treated with acupuncture at BL13 (Feishu), BL23 (Shenshu) and Dingchuan (COPD+Acupuncture, n=15), sham acupuncture (COPD+Sham, n=15) or left untreated (n=15). Exposed rats were compared with controls not exposed to CS (control, n=15). Pulmonary function was measured, and tumour necrosis factor-α (TNF-α) and interleukin-8 (IL-8) levels were determined in bronchoalveolar lavage fluid by ELISA. Histone deacetylase 2 (HDAC2) protein and mRNA expression were examined in lung tissue and in bronchus. Results Acupuncture treatment appeared to protect pulmonary function and reduce the COPD-induced inflammatory response by decreasing cell inflammation and the production of TNF-α and IL-8. Acupuncture also enhanced HDAC2 mRNA and protein expression, suggesting a possible direct effect on protein structure through post-translational modifications. Conclusions Our results suggest that acupuncture regulates inflammatory cytokines and contributes to lung protection in a rat model of smoke-induced COPD by modulating HDAC2. PMID:26345700

  14. Epithelial injury and repair in airways diseases.

    PubMed

    Grainge, Christopher L; Davies, Donna E

    2013-12-01

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

  15. Effects of Continuous Positive Airway Pressure on Cognitive Deficits in Middle-aged Patients with Obstructive Sleep Apnea Syndrome: A Meta-analysis of Randomized Controlled Trials

    PubMed Central

    Pan, Yue-Ying; Deng, Yan; Xu, Xiu; Liu, Ya-Ping; Liu, Hui-Guo

    2015-01-01

    Background: Current views on continuous positive airway pressure (CPAP) treatment to improve the cognitive deficits of patients with obstructive sleep apnea syndrome (OSAS) are controversial, so we performed a meta-analysis. Methods: A comprehensive literature search was undertaken in PubMed, CINAHL, Medline, PsycInfo, EMBASE, Cochrane Library, CNKI, WanFang, VIP, and CBMdisc for studies published from June 1971 to July 2014. The outcome measures included neuropsychological tests of the 7 cognitive domains detailed below. Results: After screening the titles and abstracts and thoroughly reading the full text, we obtained 13 studies with little risk of bias that incorporated 1744 middle-aged obese participants with mild to severe OSAS. The studies were published from 1994 to 2012. Treatment durations varied from 1 to 24 weeks. The effect sizes of attention, vigilance, processing speed, working memory, memory, verbal fluency, and visuoconstructive skills domains were −0.10 (P = 0.24), −0.12 (P = 0.04), −0.08 (P = 0.16), 0.00 (P = 0.95), −0.04 (P = 0.30), −0.06 (P = 0.34), and −0.01 (P = 0.92), respectively. Conclusions: Cognition partially improved in patients with OSAS after CPAP treatment. The only domain with significant improvement was vigilance. Rigorous randomized controlled trials need to be performed to obtain clear results. PMID:26315086

  16. The effect of treating obstructive sleep apnea with positive airway pressure on depression and other subjective symptoms: A systematic review and meta-analysis.

    PubMed

    Gupta, Madhulika A; Simpson, Fiona C; Lyons, Danika C A

    2016-08-01

    Patients with obstructive sleep apnea (OSA) frequently present with symptoms of depression and anxiety. The objective of this study is to determine if treatment with positive airway pressure (PAP) improves symptoms of depression and anxiety. A systematic review was conducted to identify clinical trials of PAP that contained a validated measure of depression severity. Meta-analysis was conducted for depression, anxiety, excessive daytime sleepiness (EDS), quality of life (QoL) and respiratory variables. The systematic review included 33 reports. Pre-post-test analysis of PAP showed a moderate effect size (Hedge's g, 95% CI) for depression 0.524 [0.401-0.647], but a low effect size compared to oral placebo (0.355 [0.187-0.524]) and no effect when compared to dental appliances (0.107 [-0.72-0.287]) and sham PAP (-0.049 [-0.292-0.194]). Anxiety, EDS, and QoL showed similar improvement in pre-post-test analysis, but a lack of superiority to dental appliances and sham PAP. PAP was superior to all comparators for respiratory variables. PAP has a moderate clinical effect on symptoms of depression and anxiety in OSA, but it is not superior to dental appliances or sham PAP. The improvement in subjective symptoms, such as depression and anxiety, may be mediated by patient expectations and contact with healthcare providers. PMID:26454823

  17. Meta-analysis of randomised controlled trials of oral mandibular advancement devices and continuous positive airway pressure for obstructive sleep apnoea-hypopnoea.

    PubMed

    Sharples, Linda D; Clutterbuck-James, Abigail L; Glover, Matthew J; Bennett, Maxine S; Chadwick, Rebecca; Pittman, Marcus A; Quinnell, Timothy G

    2016-06-01

    Obstructive sleep apnoea-hypopnoea (OSAH) causes excessive daytime sleepiness, impairs quality-of-life, and increases cardiovascular disease and road traffic accident risks. Continuous positive airway pressure (CPAP) treatment and mandibular advancement devices (MAD) have been shown to be effective in individual trials but their effectiveness particularly relative to disease severity is unclear. A MEDLINE, Embase and Science Citation Index search updating two systematic reviews to August 2013 identified 77 RCTs in adult OSAH patients comparing: MAD with conservative management (CM); MAD with CPAP; or CPAP with CM. Overall MAD and CPAP significantly improved apnoea-hypopnoea index (AHI) (MAD -9.3/hr (p < 0.001), CPAP -25.4 (p < 0.001)). In direct comparisons mean AHI and Epworth sleepiness scale score were lower (7.0/hr (p < 0.001) and 0.67 (p = 0.093) respectively) for CPAP. There were no CPAP vs. MAD trials in mild OSAH but in comparisons with CM, MAD and CPAP reduced ESS similarly (MAD 2.01 (p < 0.001); CPAP 1.23 (p = 0.012). Both MAD and CPAP are clinically effective in the treatment of OSAH. Although CPAP has a greater treatment effect, MAD is an appropriate treatment for patients who are intolerant of CPAP and may be comparable to CPAP in mild disease. PMID:26163056

  18. Management of malignant airway obstruction: clinical and dosimetric considerations using an iridium-192 afterloading technique in conjunction with the neodymium-YAG laser

    SciTech Connect

    Schray, M.F.; McDougall, J.C.; Martinez, A.; Edmundson, G.K.; Cortese, D.A.

    1985-02-01

    Fourteen patients with malignant airway obstruction have had 21 placements of a flexible nylon catheter for afterloading iridium-192 using the flexible fiberoptic bronchoscope. Prescribed therapy was completed in 13 patients (18 courses). All patients had prior full-dose external irradiation, and no effective surgical or chemotherapeutic options remained. While many have had a trial of neodymium-YAG (yttrium-aluminum-garnet) laser therapy alone, eight patients received laser treatment one to three weeks prior to planned brachytherapy to provide immediate relief of symptoms and/or facilitate access and safe catheter placement. Most patients (64%) had recurrent squamous cell lung cancer. A dose of 3000 cGy is currently specified to 5 mm and 10 mm in the bronchus and trachea, respectively. Nine of the 13 treated patients have had follow-up bronchoscopy at approximately three months post-treatment with improvement documented in seven and progression in two patients. A single patient treated with laser and 6000 rad at 5 mm developed a bronchoesophageal fistula. No other complication has been observed. The technique is simple and safe with the use of laser therapy when needed and appears to offer effective palliation in most patients even when standard therapy is exhausted.

  19. The anatomy of the dog soft palate. II. Histological evaluation of the caudal soft palate in brachycephalic breeds with grade I brachycephalic airway obstructive syndrome.

    PubMed

    Pichetto, Michela; Arrighi, Silvana; Roccabianca, Paola; Romussi, Stefano

    2011-07-01

    In brachycephalic dogs, the skull bone shortening is not paralleled by a decreased development of soft tissues. Relatively longer soft palate is one of the main factors contributing to pharyngeal narrowing during normal respiratory activity of these dog breeds, which are frequent carriers of the brachycephalic airway obstructive syndrome (BAOS), which affects most part of them during their postnatal life. No histological studies assessing the morphology and the normal tissue composition of the soft palate in brachycephalic dogs are available, neither has ever been determined whether the elongated soft palate is a primary or secondary event. Aim of this study was to describe the morphology of the caudal soft palate in brachycephalic dogs with Grade I BAOS to identify potential features possibly favoring the pathogenesis of BAOS. Specimens from brachycephalic dogs (N = 11) that underwent preventive surgery were collected from surgery, processed for histology, and examined at six transversal levels. The brachycephalic soft palates showed peculiar features such as thickened superficial epithelium, extensive oedema of the connective tissue, and mucous gland hyperplasia. Several muscular alterations were evidenced in addition. The results of this investigation add to the general knowledge of the anatomy of soft palate in the canine species and establish baseline information on the morphological basis of the soft palate thickening in brachycephalic dogs. PMID:21634020

  20. Analysis of the Airway Microbiota of Healthy Individuals and Patients with Chronic Obstructive Pulmonary Disease by T-RFLP and Clone Sequencing

    PubMed Central

    Zakharkina, Tetyana; Heinzel, Elke; Koczulla, Rembert A.; Greulich, Timm; Rentz, Katharina; Pauling, Josch K.; Baumbach, Jan; Herrmann, Mathias; Grünewald, Christiane; Dienemann, Hendrik; von Müller, Lutz; Bals, Robert

    2013-01-01

    Chronic obstructive pulmonary disease (COPD) is a progressive, inflammatory lung disease that affects a large number of patients and has significant impact. One hallmark of the disease is the presence of bacteria in the lower airways. Objective: The aim of this study was to analyze the detailed structure of microbial communities found in the lungs of healthy individuals and patients with COPD. Nine COPD patients as compared and 9 healthy individuals underwent flexible bronchoscopy and BAL was performed. Bacterial nucleic acids were subjected to terminal restriction fragment (TRF) length polymorphism and clone library analysis. Overall, we identified 326 T-RFLP band, 159 in patients and 167 in healthy controls. The results of the TRF analysis correlated partly with the data obtained from clone sequencing. Although the results of the sequencing showed high diversity, the genera Prevotella, Sphingomonas, Pseudomonas, Acinetobacter, Fusobacterium, Megasphaera, Veillonella, Staphylococcus, and Streptococcus constituted the major part of the core microbiome found in both groups. A TRF band possibly representing Pseudomonas sp. monoinfection was associated with a reduction of the microbial diversity. Non-cultural methods reveal the complexity of the pulmonary microbiome in healthy individuals and in patients with COPD. Alterations of the microbiome in pulmonary diseases are correlated with disease. PMID:23874580

  1. Nurse-led intensive interventions improve adherence to continuous positive airway pressure therapy and quality of life in obstructive sleep apnea patients

    PubMed Central

    Chen, Xiaofen; Chen, Weiting; Hu, Weijie; Huang, Kui; Huang, Jing; Zhou, Yu

    2015-01-01

    Background Continuous positive airway pressure (CPAP) is widely recommended for the treatment of sleep apnea/hypopnea syndrome (SAHS), but its usage by patients is very low. The aim of this study was to assess intensive educational programs and nursing support for the improvement of CPAP use and outcomes in SAHS patients. Methods Eighty new SAHS patients were randomized to receive nurse-led intensive interventions or usual support at hospital and home. The main outcome measure was CPAP use; changes in sleeping, symptoms, mood, and quality of life were also assessed after 12 months of treatment. Results All outcome measures were improved after treatment in both groups. However, patients receiving intensive support with significantly higher CPAP use (higher daily CPAP usage by 2.2 hours/day) had greater improvements in SAHS symptoms and mood (P<0.05). The intervention group further showed an improvement in the Short Form-36 domains of mental and physical health (P<0.05). Conclusion The CPAP usage and quality of life can be significantly improved by nurse-led intensive program in obstructive sleep apnea patients. PMID:26648703

  2. Adult obstructive sleep apnoea.

    PubMed

    Jordan, Amy S; McSharry, David G; Malhotra, Atul

    2014-02-22

    Obstructive sleep apnoea is an increasingly common disorder of repeated upper airway collapse during sleep, leading to oxygen desaturation and disrupted sleep. Features include snoring, witnessed apnoeas, and sleepiness. Pathogenesis varies; predisposing factors include small upper airway lumen, unstable respiratory control, low arousal threshold, small lung volume, and dysfunctional upper airway dilator muscles. Risk factors include obesity, male sex, age, menopause, fluid retention, adenotonsillar hypertrophy, and smoking. Obstructive sleep apnoea causes sleepiness, road traffic accidents, and probably systemic hypertension. It has also been linked to myocardial infarction, congestive heart failure, stroke, and diabetes mellitus though not definitively. Continuous positive airway pressure is the treatment of choice, with adherence of 60-70%. Bi-level positive airway pressure or adaptive servo-ventilation can be used for patients who are intolerant to continuous positive airway pressure. Other treatments include dental devices, surgery, and weight loss. PMID:23910433

  3. Micro- and macrorheology of mucus

    PubMed Central

    Lai, Samuel K.; Wang, Ying-Ying; Wirtz, Denis; Hanes, Justin

    2009-01-01

    Mucus is a complex biological material that lubricates and protects the human lungs, gastrointestinal (GI) tract, vagina, eyes, and other moist mucosal surfaces. Mucus serves as a physical barrier against foreign particles, including toxins, pathogens, and environmental ultrafine particles, while allowing rapid passage of selected gases, ions, nutrients, and many proteins. Its selective barrier properties are precisely regulated at the biochemical level across vastly different length scales. At the macroscale, mucus behaves as a non-Newtonian gel, distinguished from classical solids and liquids by its response to shear rate and shear stress, while, at the nanoscale, it behaves as a low viscosity fluid. Advances in the rheological characterization of mucus from the macroscopic to nanoscopic levels have contributed critical understanding to mucus physiology, disease pathology, and the development of drug delivery systems designed for use at mucosal surfaces. This article reviews the biochemistry that governs mucus rheology, the macro- and microrheology of human and laboratory animal mucus, rheological techniques applied to mucus, and the importance of an improved understanding of the physical properties of mucus to advancing the field of drug and gene delivery. PMID:19166889

  4. Overnight urinary uric acid: creatinine ratio for detection of sleep hypoxemia. Validation study in chronic obstructive pulmonary disease and obstructive sleep apnea before and after treatment with nasal continuous positive airway pressure.

    PubMed

    Braghiroli, A; Sacco, C; Erbetta, M; Ruga, V; Donner, C F

    1993-07-01

    During hypoxia ATP degradation to uric acid is increased in animal models and humans. To assess the reliability of an overnight increase in uric acid excretion as a marker of nocturnal hypoxemia, we selected 10 normal volunteers (7 males and 3 females), 29 COPD patients (26 males and 3 females), and 49 subjects with obstructive sleep apnea (OSA) (43 males and 6 females). The patients underwent standard polysomnography, which was repeated in 14 subjects with nasal continuous positive airway pressure (CPAP), and were subdivided into two groups: Group D included desaturating subjects who spent at least 1 h at SaO2 < 90% and 15 min below 85%, and Group ND were nondesaturating subjects. The overnight change in the uric acid:creatinine ratio (delta UA:Cr) was negative in normal subjects (-27.5 +/- 9.1 [mean +/- SD]) and ND groups: -19.7 +/- 14.3 in COPD, -16.1 +/- 13.0 in OSA. In both COPD and OSA Group D, the ratio was usually positive: delta UA:Cr was 17.9 +/- 31.4 in Group D COPD (p < 0.001 versus ND) and 10.1 +/- 30.7 in Group D OSA (p < 0.001 versus ND and versus normal subjects) despite 4 of 15 false negative results in COPD and 8 of 20 in OSA. CPAP effective treatment induced a marked reduction ((p = 0.0024) in delta UA:Cr, leading to a negative value. We conclude that delta UA:Cr seems to be a promising index of significant nocturnal tissue hypoxia, with good specificity but poor sensitivity (about 30% false negative), which might be useful for the long-term follow-up of outpatients on nasal CPAP with a positive ratio at baseline. PMID:8317794

  5. Can Continuous Positive Airway Pressure Reduce the Risk of Stroke in Obstructive Sleep Apnea Patients? A Systematic Review and Meta-Analysis

    PubMed Central

    Kim, Yeshin; Koo, Yong Seo; Lee, Hee Young; Lee, Seo-Young

    2016-01-01

    Background and Purpose Obstructive sleep apnea (OSA) has been shown to increase the risk of stroke. Although continuous positive airway pressure (CPAP) is considered the treatment of choice for OSA, whether treating OSA with CPAP reduces the risk of stroke remains unclear. We aimed to evaluate the effects of CPAP on incidence of stroke in patients with OSA. Materials and Methods We conducted a systematic review and meta-analysis of all published studies that provided the number of incident strokes in OSA patients in light of their treatment status with CPAP. Results We identified 8 relevant studies: one randomized controlled study (RCT), 5 cohort studies, and 2 studies using administrative health data. The two overlapping cohort studies in women and the elderly and the 2 studies using administrative health data had analyzed the impact of CPAP on stroke apart from cardiac events, whereas the others had focused on the overall cardiovascular events. Based on a meta-analysis of the cohort studies, treatment with CPAP was associated with a lower incidence of stroke and cardiac events with relative risks of 0.27 [0.14–0.53], and 0.54 [0.38–0.75], respectively, although this could not be reproduced in the RCT and the studies using administrative data. Conclusions Treating with CPAP in patients with OSA might decrease the risk of stroke, although there is some conflicting evidence. Such effect was more pronounced in stroke than in cardiac events. Future studies analyzing stroke apart from cardiac disease would be of interest. PMID:26731604

  6. The Efficacy of Continuous Positive Airway Pressure Therapy on Nocturia in Patients With Obstructive Sleep Apnea: A Systematic Review and Meta-Analysis

    PubMed Central

    Wang, Tao; Huang, Wei; Zong, Huantao; Zhang, Yong

    2015-01-01

    Purpose: To assess the efficacy of the continuous positive airway pressure (CPAP) on nocturia in patients with obstructive sleep apnea (OSA). Methods: A literature review was performed to identify all published clinical trials of CPAP for the treatment of nocturia. The search included the following databases: MEDLINE, Embase, and the Cochrane Controlled Trials Register. The reference lists of the retrieved studies were also investigated. Results: Five publications involving a total of 307 patients were used in the analysis, which compared the number of incidents of nocturia before and after CPAP treatment. We found that patients with OSA and nocturia who were treated with CPAP had a significant decrease in the frequency of nocturia and the volume of urine associated with it. The mean number of nocturia incidents (standardized mean difference [SMD], –2.28; 95% confidence interval [CI], –2.42 to –2.15; P<0.00001) and the associated urine volume (SMD, –183.12; 95% CI, –248.27 to –117.98; P<0.00001) indicated that CPAP was effective. Besides, the Epworth Sleepiness Scale (SMD, –5.88; 95% CI, –6.56 to –5.21; P<0.00001) and the CPAP apnea-hypopnea index (SMD, –31.57; 95% CI, –33.87 to –29.28; P<0.00001) indicated that CPAP significantly improved the quality of sleep. Conclusions: This meta-analysis indicates that CPAP maybe an effective treatment for reducing nocturia associated with OSA and improving the quality of life of such patients. PMID:26620900

  7. Effects of continuous positive airway pressure on blood pressure in patients with resistant hypertension and obstructive sleep apnea: a meta-analysis

    PubMed Central

    Iftikhar, Imran H.; Valentine, Christopher W.; Bittencourt, Lia R.A.; Cohen, Debbie L.; Fedson, Annette C.; Gíslason, Thorarinn; Penzel, Thomas; Phillips, Craig L.; Yu-sheng, Lin; Pack, Allan I.; Magalang, Ulysses J.

    2015-01-01

    Objective To systematically analyze the studies that have examined the effect of continuous positive airway pressure (CPAP) on blood pressure (BP) in patients with resistant hypertension and obstructive sleep apnea (OSA). Methods Design – meta-analysis of observational studies and randomized controlled trials (RCTs) indexed in PubMed and Ovid (All Journals@Ovid). participants: individuals with resistant hypertension and OSA; interventions – CPAP treatment. Results A total of six studies met the inclusion criteria for preintervention to postintervention analyses. The pooled estimates of mean changes after CPAP treatment for the ambulatory (24-h) SBP and DBP from six studies were −7.21 mmHg [95% confidence interval (CI): −9.04 to −5.38; P <0.001; I2 58%) and −4.99 mmHg (95% CI: −6.01 to −3.96; P <0.001; I2 31%), respectively. The pooled estimate of the ambulatory SBP and DBP from the four RCTs showed a mean net change of −6.74 mmHg [95% CI: −9.98 to −3.49; P <0.001; I2 61%] and −5.94 mmHg (95% CI: −9.40 to −2.47; P =0.001; I2 76%), respectively, in favor of the CPAP group. Conclusion The pooled estimate shows a favorable reduction of BP with CPAP treatment in patients with resistant hypertension and OSA. The effects sizes are larger than those previously reported in patients with OSA without resistant hypertension. PMID:25243523

  8. The Duration of an Exposure Response Gradient between Incident Obstructive Airways Disease and Work at the World Trade Center Site: 2001-2011

    PubMed Central

    Hall, Charles B.; Liu, Xiaoxue; Zeig-Owens, Rachel; Webber, Mayris P.; Aldrich, Thomas K.; Weakley, Jessica; Schwartz, Theresa; Cohen, Hillel W.; Glaser, Michelle S.; Olivieri, Brianne L.; Weiden, Michael D.; Nolan, Anna; Kelly, Kerry J.; Prezant, David J.

    2015-01-01

    Background: Adverse respiratory effects of World Trade Center (WTC) exposure have been widely documented, but the length of time that exposure remains associated with disease is uncertain. We estimate the incidence of new cases of physician-diagnosed obstructive airway disease (OAD) as a function of time since 9/11/2001 in WTC-exposed firefighters. Methods: Exposure was categorized by first WTC arrival time: high (9/11/2001 AM); moderate (9/11/2001 PM or 9/12/2001); or low (9/13-24/2001). We modeled relative rates (RR) and 95% confidence intervals (CI) of OAD incidence by exposure over the first 10 years post-9/11/2001, estimating the time(s) of change in the RR with change point models. We further examined the relationship between self-reported lower respiratory symptoms and physician diagnoses. Results: Change points were observed at 15 and 84 months post-9/11/2001, with relative incidence rates for the high versus low exposure group of 4.02 (95% CI 2.62-6.16) prior to 15 months, 1.90 (95% CI 1.49-2.44) from months 16 to 84, and 1.20 (95% CI 0.92-1.56) thereafter. Incidence in all exposure groups increased after the WTC health program began to offer free coverage of OAD medications in month 63. Self-reported lower respiratory symptoms in the first 15 months had 80.6% sensitivity, but only 35.9% specificity, for eventual OAD diagnoses. Conclusions: New OAD diagnoses are associated with WTC exposure for at least seven years. Some portion of the extended duration of that association may be due to delayed diagnoses. Nevertheless, our results support recognizing OAD among rescue workers as WTC-related even when diagnosed years after exposure. PMID:26064784

  9. Acute effects of different levels of continuous positive airway pressure on cardiac autonomic modulation in chronic heart failure and chronic obstructive pulmonary disease

    PubMed Central

    Reis, Michel S.; Sampaio, Luciana M.M.; Lacerda, Diego; De Oliveira, Luis V.F.; Pereira, Guilherme B.; Pantoni, Camila B.F.; Thommazo, Luciana Di; Catai, Aparecida M.

    2010-01-01

    Introduction Non-invasive ventilation may improve autonomic modulation and ventilatory parameters in severely disabled patients. The aim of the present study was to evaluate the physiological influence of acute treatment with different levels of continuous positive airway pressure (CPAP) on the autonomic balance of heart and respiratory responses in patients with stable chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF). Materials and methods A COPD group (n = 10), CHF group (n = 8) and healthy subjects (n = 10) were evaluated. The participants were randomized to receive three different levels of CPAP on the same day: sham ventilation (Sham), 5 cmH20 (CPAP5) and 10 cmH20 (CPAP10) for 10 min. Respiratory rate, end tidal carbon dioxide (ETCO2), peripheral oxygen saturation (SpO2), heart rate (HR), blood pressure and heart rate variability in the time and frequency domains were measured during spontaneous breathing and under the sham, CPAP5 and CPAP10 conditions. Results All groups experienced a reduction in ETCO2 values during treatment with CPAP (p < 0.05). CPAP increased SpO2 and HR in the COPD group (p < 0.05). The COPD group also had lower RMSSD values during treatment with different levels of CPAP when compared to the control group (p < 0.05). In the CHF group, CPAP5 and CPAP10 increased the SDNN value (p < 0.05). CPAP10 reduced the SDNN value in the COPD group (p < 0.05). Conclusion The findings suggest that CPAP may cause improvements in the neural control of heart rate in patients with stable COPD and CHF. For each patient, the “best CPAP level” should be defined as the best respiratory response and autonomic balance. PMID:22419931

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

    PubMed Central

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

    2015-01-01

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

  11. Lubiprostone Decreases Mouse Colonic Inner Mucus Layer Thickness and Alters Intestinal Microbiota

    PubMed Central

    Musch, Mark W.; Wang, Yunwei; Claud, Erika C.

    2013-01-01

    Background Lubiprostone has been used to treat constipation through its effects to stimulate Cl− secretion, resulting in water and electrolyte secretion. Aim Potential associated changes in intestinal mucus and the colonizing bacteria (microbiome) have not been studied. As mucus obstructions may play a role in cystic fibrosis, the hypothesis that lubiprostone alters intestinal mucus and the microbiome was investigated. Methods Ion transport studies were performed ex vivo. For mucus and microbiome studies, mice were gavaged daily with lubiprostone or vehicle. Mucin from intestinal sections was analyzed in Carnoy’s fixed tissues stained with Alcian blue. Microbiome composition was analyzed by 16S rRNA gene-based sequencing. Results Lubiprostone stimulated short circuit current in all mouse intestinal segments after both serosal and mucosal additions, albeit at lower concentrations in the latter. Current was Cl-dependent and blocked by mucosal diphenylcarboxylic acid, serosal bumetanide, and serosal Ba++. The CFTR inhibitor CFTRinh172 had a marginal effect. Mucus near epithelial cells (inner layer mucus) was not present in the small intestine of any mice. Proximal colon inner mucus layer was thicker in ΔF/ΔF compared with +/ΔF and +/+ mice. Lubiprostone decreased inner mucus layer thickness in both proximal and distal colon of all mice. Furthermore, lubiprostone altered the intestinal microbiome by increasing abundance of Lactobacillus and Alistipes. Conclusions Lubiprostone activates non-CFTR Cl− secretion and alters the colonic inner mucus layer, which is associated with changes in the composition of the enteric microbiome. PMID:23329012

  12. Arginase inhibition prevents inflammation and remodeling in a guinea pig model of chronic obstructive pulmonary disease.

    PubMed

    Pera, T; Zuidhof, A B; Smit, M; Menzen, M H; Klein, T; Flik, G; Zaagsma, J; Meurs, H; Maarsingh, H

    2014-05-01

    Airway inflammation and remodeling are major features of chronic obstructive pulmonary disease (COPD), whereas pulmonary hypertension is a common comorbidity associated with a poor disease prognosis. Recent studies in animal models have indicated that increased arginase activity contributes to features of asthma, including allergen-induced airway eosinophilia and mucus hypersecretion. Although cigarette smoke and lipopolysaccharide (LPS), major risk factors for COPD, may increase arginase expression, the role of arginase in COPD is unknown. This study aimed to investigate the role of arginase in pulmonary inflammation and remodeling using an animal model of COPD. Guinea pigs were instilled intranasally with LPS or saline twice weekly for 12 weeks and pretreated by inhalation of the arginase inhibitor 2(S)-amino-6-boronohexanoic acid (ABH) or vehicle. Repeated LPS exposure increased lung arginase activity, resulting in increased l-ornithine/l-arginine and l-ornithine/l-citrulline ratios. Both ratios were reversed by ABH. ABH inhibited the LPS-induced increases in pulmonary IL-8, neutrophils, and goblet cells as well as airway fibrosis. Remarkably, LPS-induced right ventricular hypertrophy, indicative of pulmonary hypertension, was prevented by ABH. Strong correlations were found between arginase activity and inflammation, airway remodeling, and right ventricular hypertrophy. Increased arginase activity contributes to pulmonary inflammation, airway remodeling, and right ventricular hypertrophy in a guinea pig model of COPD, indicating therapeutic potential for arginase inhibitors in this disease. PMID:24563530

  13. Arylhydrocarbon receptor (AhR) activation in airway epithelial cells induces MUC5AC via reactive oxygen species (ROS) production.

    PubMed

    Chiba, Takahito; Uchi, Hiroshi; Tsuji, Gaku; Gondo, Hisaki; Moroi, Yoichi; Furue, Masutaka

    2011-02-01

    The dioxins and dioxin-like compounds in cigarette smoke regulate various immunological responses via the arylhydrocarbon receptor (AhR). These environmental toxicants are known to cause bronchitis, asthma, chronic obstructive pulmonary disease (COPD), and lung cancer. Recent studies have demonstrated that AhR activation upregulates the expression of mucin 5AC, oligomeric mucus/gel-forming (MUC5AC) in the airway epithelial cell line. However, the mechanism for the production of mucin has not been clarified. In this study, we investigated the role and pathway of AhR in airway epithelial cells by using selective agonists and antagonists. After stimulation with or without benzopyrene (B[a]P), an AhR agonist, MUC5AC expression was measured by real-time RT-PCR. The mechanism of AhR-induced MUC5AC expression in airway epithelial cells was studied in terms of the production of cytokine and reactive oxygen species (ROS). Treatment with B[a]P increased ROS generation in NCI-H₂₉₂ cells. Furthermore, B[a]P-induced MUC5AC upregulation and mucin production were inhibited by AhR siRNA or the use of an antioxidative agent. These results suggest that the AhR-induced increase of mucin production is partially mediated by ROS generation. An antioxidant therapy approach may help to cure AhR-induced mucus hypersecretory diseases. PMID:20709182

  14. Human cervical mucus: research update.

    PubMed

    Katz, D F

    1991-12-01

    Evaluation of cervical mucus is a standard for determining the fertile period in natural family planning. Cervical mucus accepts, filters, prepares, and releases sperm for successful transport to the egg and fertilization. Recent scientific advances provide answers to how the mucus regulates fertility as its physical properties change during the menstrual cycle. Transmission electron microscopy reveals small interstices between mucus macromolecules relative to a sperm head. Thus advancing sperm must push aside or cut through the microstructure. The interstices are largest in the periovulatory phase of the cycle. Small magnetic spheres, comparable with the size of a sperm head, are now being used to study the physical properties of the mucus on the scale of individual sperm. PMID:1755453

  15. Lung protease/anti-protease network and modulation of mucus production and surfactant activity.

    PubMed

    Garcia-Verdugo, Ignacio; Descamps, Delphyne; Chignard, Michel; Touqui, Lhousseine; Sallenave, Jean-Michel

    2010-11-01

    Lung epithelium guarantees gas-exchange (performed in the alveoli) and protects from external insults (pathogens, pollutants…) present within inhaled air. Both functions are facilitated by secretions lining airway surface liquid, mucus (in the upper airways) and pulmonary surfactant (in the alveoli). Mucins, the main glycoproteins present within the mucus, are responsible for its rheologic properties and participate in lung defense mechanisms. In parallel, lung collectins are pattern recognition molecules present in pulmonary surfactant that also modulate lung defense. During chronic airways diseases, excessive protease activity can promote mucus hypersecretion and degradation of lung collectins and therefore contribute to the pathophysiology of these diseases. Importantly, secretion of local and systemic anti-proteases might be crucial to equilibrate the protease/anti-protease unbalance and therefore preserve the function of lung host defense compounds and airway surface liquid homeostasis. In this review we will present information relative to proteases able to modulate mucin production and lung collectin integrity, two important compounds of innate immune defense. One strategy to preserve physiological mucus production and collectin integrity during chronic airways diseases might be the over-expression of local 'alarm' anti-proteases such as SLPI and elafin. Interestingly, a cross-talk between lung collectins and anti-protease activity has recently been described, implicating the presence within the lung of a complex network between proteases, anti-proteases and pattern recognition molecules, which aims to keep or restore homeostasis in resting or inflamed lungs. PMID:20493919

  16. Cytokines in the pathogenesis of chronic obstructive pulmonary disease.

    PubMed

    Reid, P T; Sallenave, J-M

    2003-01-01

    Chronic obstructive pulmonary disease (COPD) is a common cause of morbidity and mortality. The term is heterogenous and encompasses a number of distinct but often overlapping phenotypes including chronic bronchitis, small airways obstruction, emphysema and in some individuals, a systemic component. Although there have been significant advances in understanding the pathophysiology of COPD, understanding of the role of the inflammation in the pathogenesis of the condition remains in its infancy. Indeed, cytokines that are known to orchestrate the inflammatory response in asthma and other inflammatory diseases are only beginning to be reported in COPD. In this review, we highlight the potential role of cytokines in the development of mucus hypersecretion observed in chronic bronchitis and the morphological changes observed in the small airways and airspaces contributing to the development of airflow limitation and respiratory failure respectively. We report evidence that exacerbations are linked to increased expression of pro-inflammatory cytokines and that the wasting and skeletal muscle dysfunction observed in some patients is most probably related to the presence of a systemic inflammatory response. In addition transgenic and gene therapy technology has been used to explore the temporal and co-ordinated role of cytokines in the development of COPD animal models. Enhanced understanding of the events involved in the pathogenesis of COPD will lead to the development of therapy with potential to modify the observed progressive decline in lung function and impact on the development of the illness. PMID:12570672

  17. On the effect of mucus rheology on the muco-ciliary transport.

    PubMed

    Sedaghat, M H; Shahmardan, M M; Norouzi, M; Nazari, M; Jayathilake, P G

    2016-02-01

    A two dimensional numerical model is used to study the muco-ciliary transport process in human respiratory tract. Here, hybrid finite difference-lattice Boltzmann method is used to model the flow physics of the transport of mucus and periciliary liquid (PCL) layer in the airway surface liquid. The immersed boundary method is also used to implement the propulsive effect of the cilia and also the effects of the interface between the mucus and PCL layers. The main contribution of this study is on elucidating the role of the viscoelastic behavior of mucus on the muco-ciliary transport and for this purpose an Oldroyd-B model is used as the constitutive equation of mucus for the first time. Results show that the viscosity and viscosity ratio of mucus have an enormous effect on the muco-ciliary transport process. It is also seen that the mucus velocity is affected by mucus relaxation time when its value is less than 0.002 s. Results also indicate that the variation of these properties on the mucus velocity at lower values of viscosity ratio is more significant. PMID:26656465

  18. Jaw thrust can deteriorate upper airway patency.

    PubMed

    von Ungern-Sternberg, B S; Erb, T O; Frei, F J

    2005-04-01

    Upper airway obstruction is a frequent problem in spontaneously breathing children undergoing anesthesia or sedation procedures. Failure to maintain a patent airway can rapidly result in severe hypoxemia, bradycardia, or asystole, as the oxygen demand of children is high and oxygen reserve is low. We present two children with cervical masses in whom upper airway obstruction exaggerated while the jaw thrust maneuver was applied during induction of anesthesia. This deterioration in airway patency was probably caused by medial displacement of the lateral tumorous tissues which narrowed the pharyngeal airway. PMID:15777312

  19. Mucus glycoprotein secretion by tracheal explants: effects of pollutants

    SciTech Connect

    Last, J.A.; Kaizu, T.

    1980-04-01

    Tracheal slices incubated with radioactive precursors in tissue culture medium secrete labeled mucus glycoproteins into the culture medium. We have used an in vivtro approach, a combined method utilizing exposure to pneumotoxins in vivo coupled with quantitation of mucus secretion rates in vitro, to study the effects of inhaled pollutants on mucus biosynthesis by rat airways. In addition, we have purified the mucus glycoproteins secreted by rat tracheal explants in order to determine putative structural changes that might by the basis for the observed augmented secretion rates after exposure of rats to H2SO4 aerosols in combination with high ambient levels of ozone. After digestion with papain, mucus glycoproteins secreted by tracheal explants may be separated into five fractions by ion-exchange chromatography, with recovery in high yield, on columns of DEAE-cellulose. Each of these five fractions, one neutral and four acidic, migrates as a single unique spot upon cellulose acetate electrophoresis at pH values of 8.6 and 1.2. The neutral fraction, which is labeled with (3H) glucosamine, does not contain radioactivity when Na2 35SO4 is used as the precursor. Acidic fractions I to IV are all labeled with either 3H-glucosamine or Na2 35SO4 as precursor. Acidic fraction II contains sialic acid as the terminal sugar on its oligosaccharide side chains, based upon its chromatographic behavior on columns of wheat-germ agglutinin-Agarose. Treatment of this fraction with neuraminidase shifts its elution position in the gradient to a lower salt concentration, coincident with acidic fraction I. After removal of terminal sialic acid residues with either neuraminidase or low pH treatment, the resultant terminal sugar on the oligosaccharide side chains is fucose. These results are identical with those observed with mucus glycoproteins secreted by cultured human tracheal explants and purified by these same techniques.

  20. Nasal continuous positive airway pressure (nCPAP) treatment for obstructive sleep apnea, road traffic accidents and driving simulator performance: a meta-analysis.

    PubMed

    Antonopoulos, Constantine N; Sergentanis, Theodoros N; Daskalopoulou, Styliani S; Petridou, Eleni Th

    2011-10-01

    We used meta-analysis to synthesize current evidence regarding the effect of nasal continuous positive airway pressure (nCPAP) on road traffic accidents in patients with obstructive sleep apnea (OSA) as well as on their performance in driving simulator. The primary outcomes were real accidents, near miss accidents, and accident-related events in the driving simulator. Pooled odds ratios (ORs), incidence rate ratios (IRRs) and standardized mean differences (SMDs) were appropriately calculated through fixed or random effects models after assessing between-study heterogeneity. Furthermore, risk differences (RDs) and numbers needed to treat (NNTs) were estimated for real and near miss accidents. Meta-regression analysis was performed to examine the effect of moderator variables and publication bias was also evaluated. Ten studies on real accidents (1221 patients), five studies on near miss accidents (769 patients) and six studies on the performance in driving simulator (110 patients) were included. A statistically significant reduction in real accidents (OR=0.21, 95% CI=0.12-0.35, random effects model; IRR=0.45, 95% CI=0.34-0.59, fixed effects model) and near miss accidents (OR=0.09, 95% CI=0.04-0.21, random effects model; IRR=0.23, 95% CI=0.08-0.67, random effects model) was observed. Likewise, a significant reduction in accident-related events was observed in the driving simulator (SMD=-1.20, 95% CI=-1.75 to -0.64, random effects). The RD for real accidents was -0.22 (95% CI=-0.32 to -0.13, random effects), with NNT equal to five patients (95% CI=3-8), whereas for near miss accidents the RD was -0.47 (95% CI=-0.69 to -0.25, random effects), with NNT equal to two patients (95% CI=1-4). For near miss accidents, meta-regression analysis suggested that nCPAP seemed more effective among patients entering the studies with higher baseline accident rates. In conclusion, all three meta-analyses demonstrated a sizeable protective effect of nCPAP on road traffic accidents, both

  1. Immunostimulation of bronchoalveolar lavage cells from recurrent airway obstruction-affected horses by different CpG-classes bound to gelatin nanoparticles.

    PubMed

    Klier, John; May, Anna; Fuchs, Sebastian; Schillinger, Ulrike; Plank, Christian; Winter, Gerhard; Gehlen, Heidrun; Coester, Conrad

    2011-11-15

    Recurrent airway obstruction (RAO) in horses has become a common problem in stabled horses in industrialized countries and deserves new therapeutic strategies. CpG-oligodeoxynucleotides (CpG-ODNs) were developed as effective immunostimulating agents to induce a Th2/Th1 shift. These agents showed a beneficial therapeutic effect in allergic diseases with predominant Th2 immunoresponse. CpG-ODN delivery by gelatin nanoparticles (GNPs) resulted in enhanced cellular uptake in murine and human in vitro studies and was a starting point for the present trial. The aim of this study was to identify an optimal stimulating CpG motif in horses with regard to species specificity on equine bronchoalveolar lavage (BAL) cells, in terms of a possible specific immunomodulation effect (Th2/Th1 shift) by used CpG-ODN. Accordingly, GNPs were evaluated as a delivery system to improve CpG-ODN immunostimulation in equine BAL cells. BAL fluid (BALF) was obtained from seven horses with moderate RAO and from four healthy horses and was subsequently incubated with five different CpG-ODN sequences (from A-, B- and C-class) and one ODN without any CpG motif. Release of three key cytokines (IL-4, IL-10 and IFN-γ) was quantified by ELISA to detect an allergy mediated Th2 immunoresponse (IL-4) as well as a proinflammatory Th1 response (IFN-γ). Due to its specific anti-inflammatory and anti-allergic effects, IL-10 was considered as a beneficial agent in pathophysiology of RAO. Results showed a significant upregulation of IL-10 and IFN-γ on the one hand and a downregulation of IL-4 on the other hand in RAO affected horses. Cell cultures from healthy horses had a significantly stronger response in cytokine release to all the applied stimuli in contrast to RAO derived cells. Comparing all five CpG sequences, A-class 2216 significantly showed the highest immunomodulatory effects on equine BALF cells and, hence, was chosen for follow-up preliminary clinical studies. PMID:21831455

  2. Tachykinin antagonists and the airways.

    PubMed

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

    1995-01-01

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

  3. Influence of two-phase gas-liquid interaction on aerosol deposition in airways.

    PubMed

    Kim, C S; Abraham, W M; Chapman, G A; Sackner, M A

    1985-04-01

    Many patients with chronic simple bronchitis, viz., chronic productive cough without major airway obstruction, frequently show enhanced aerosol deposition in the airways. We hypothesized that this phenomenon might relate in part to wave motion of an accumulated layer of mucus caused by dynamic, two-phase gas-liquid interactions. In the present investigation, two-phase gas-liquid interaction was demonstrated in vivo by observing wave motion during tidal breathing of radiopaque-labeled viscous and viscoelastic fluids that had been added to distal tracheas of conscious sheep. Total aerosol deposition in the lung and mean pulmonary resistance (RL) were measured after addition of 4 to 10 ml of viscoelastic or viscous fluids to the distal main bronchi of conscious sheep. Change in aerosol deposition over baseline after fluid addition was compared with change in RL. In 21 experiments, 5 for each of 3 viscoelastic fluids with varying characteristics and 6 for a viscous fluid, aerosol deposition was significantly enhanced in every experiment, irrespective of the type of fluid added. This increase in aerosol deposition ranged from 13 to 66% above baseline. The RL increased in 5 of the 6 experiments with viscous fluid and in 4 of the 15 experiments with viscoelastic fluids. There was less wavelike motion with viscous than with viscoelastic fluids. These results suggest that two-phase gas-liquid interaction in the airways can account for increased aerosol deposition with little alteration in airway resistance. PMID:3994158

  4. A Novel Nonhuman Primate Model of Cigarette Smoke–Induced Airway Disease

    PubMed Central

    Polverino, Francesca; Doyle-Eisele, Melanie; McDonald, Jacob; Wilder, Julie A.; Royer, Christopher; Laucho-Contreras, Maria; Kelly, Emer M.; Divo, Miguel; Pinto-Plata, Victor; Mauderly, Joe; Celli, Bartolome R.; Tesfaigzi, Yohannes; Owen, Caroline A.

    2016-01-01

    Small animal models of chronic obstructive pulmonary disease (COPD) have several limitations for identifying new therapeutic targets and biomarkers for human COPD. These include a pulmonary anatomy that differs from humans, the limited airway pathologies and lymphoid aggregates that develop in smoke-exposed mice, and the challenges associated with serial biological sampling. Thus, we assessed the utility of cigarette smoke (CS)–exposed cynomolgus macaque as a nonhuman primate (NHP) large animal model of COPD. Twenty-eight NHPs were exposed to air or CS 5 days per week for up to 12 weeks. Bronchoalveolar lavage and pulmonary function tests were performed at intervals. After 12 weeks, we measured airway pathologies, pulmonary inflammation, and airspace enlargement. CS-exposed NHPs developed robust mucus metaplasia, submucosal gland hypertrophy and hyperplasia, airway inflammation, peribronchial fibrosis, and increases in bronchial lymphoid aggregates. Although CS-exposed NHPs did not develop emphysema over the study time, they exhibited pathologies that precede emphysema development, including increases in the following: i) matrix metalloproteinase-9 and proinflammatory mediator levels in bronchoalveolar lavage fluid, ii) lung parenchymal leukocyte counts and lymphoid aggregates, iii) lung oxidative stress levels, and iv) alveolar septal cell apoptosis. CS-exposed NHPs can be used as a model of airway disease occurring in COPD patients. Unlike rodents, NHPs can safely undergo longitudinal sampling, which could be useful for assessing novel biomarkers or therapeutics for COPD. PMID:25542772

  5. A novel nonhuman primate model of cigarette smoke-induced airway disease.

    PubMed

    Polverino, Francesca; Doyle-Eisele, Melanie; McDonald, Jacob; Wilder, Julie A; Royer, Christopher; Laucho-Contreras, Maria; Kelly, Emer M; Divo, Miguel; Pinto-Plata, Victor; Mauderly, Joe; Celli, Bartolome R; Tesfaigzi, Yohannes; Owen, Caroline A

    2015-03-01

    Small animal models of chronic obstructive pulmonary disease (COPD) have several limitations for identifying new therapeutic targets and biomarkers for human COPD. These include a pulmonary anatomy that differs from humans, the limited airway pathologies and lymphoid aggregates that develop in smoke-exposed mice, and the challenges associated with serial biological sampling. Thus, we assessed the utility of cigarette smoke (CS)-exposed cynomolgus macaque as a nonhuman primate (NHP) large animal model of COPD. Twenty-eight NHPs were exposed to air or CS 5 days per week for up to 12 weeks. Bronchoalveolar lavage and pulmonary function tests were performed at intervals. After 12 weeks, we measured airway pathologies, pulmonary inflammation, and airspace enlargement. CS-exposed NHPs developed robust mucus metaplasia, submucosal gland hypertrophy and hyperplasia, airway inflammation, peribronchial fibrosis, and increases in bronchial lymphoid aggregates. Although CS-exposed NHPs did not develop emphysema over the study time, they exhibited pathologies that precede emphysema development, including increases in the following: i) matrix metalloproteinase-9 and proinflammatory mediator levels in bronchoalveolar lavage fluid, ii) lung parenchymal leukocyte counts and lymphoid aggregates, iii) lung oxidative stress levels, and iv) alveolar septal cell apoptosis. CS-exposed NHPs can be used as a model of airway disease occurring in COPD patients. Unlike rodents, NHPs can safely undergo longitudinal sampling, which could be useful for assessing novel biomarkers or therapeutics for COPD. PMID:25542772

  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. Tensiometric and Phase Domain Behavior of Lung Surfactant on Mucus-like Viscoelastic Hydrogels.

    PubMed

    Schenck, Daniel M; Fiegel, Jennifer

    2016-03-01

    Lung surfactant has been observed at all surfaces of the airway lining fluids and is an important contributor to normal lung function. In the conducting airways, the surfactant film lies atop a viscoelastic mucus gel. In this work, we report on the characterization of the tensiometric and phase domain behavior of lung surfactant at the air-liquid interface of mucus-like viscoelastic gels. Poly(acrylic acid) hydrogels were formulated to serve as a model mucus with bulk rheological properties that matched those of tracheobronchial mucus secretions. Infasurf (Calfactant), a commercially available pulmonary surfactant derived from calf lung extract, was spread onto the hydrogel surface. The surface tension lowering ability and relaxation of Infasurf films on the hydrogels was quantified and compared to Infasurf behavior on an aqueous subphase. Infasurf phase domains during surface compression were characterized by fluorescence microscopy and phase shifting interferometry. We observed that increasing the bulk viscoelastic properties of the model mucus hydrogels reduced the ability of Infasurf films to lower surface tension and inhibited film relaxation. A shift in the formation of Infasurf condensed phase domains from smaller, more spherical domains to large, agglomerated, multilayer structures was observed with increasing viscoelastic properties of the subphase. These studies demonstrate that the surface behavior of lung surfactant on viscoelastic surfaces, such as those found in the conducting airways, differs significantly from aqueous, surfactant-laden systems. PMID:26894883

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

    PubMed

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

    2016-03-01

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

  9. 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

  10. [Mucoceles of the minor salivary glands. Extravasation mucoceles (mucus granulomas) and retention mucoceles (mucus retention cysts) (author's transl)].

    PubMed

    Seifert, G; Donath, K; von Gumberz, C

    1981-06-01

    360 cases of salivary glands cysts (= 6%) were collected in the Salivary Glands Register (Institute of Pathology, University of Hamburg) from 1965 until 1979 among a total of 5739 register cases. 273 cases of the cystic lesions (= 76%) were mucoceles of the minor salivary glands. The analysis of these 273 cases revealed the following results: 1. Two types of mucoceles can be morphologically distinguished: extravasation mucoceles and retention mucoceles. 2. The extravasation mucocele is in our material (240 cases = 88.7%) the most frequent type of mucocele. The term "extravasation mucocele" of the anglo-american literature is identical with the term "mucus granuloma" ("Schleimgranulom") introduced by Hamperl (1932). 3. The main signs of the mucus granulomas are: predominant location (79%) at the lower lip, age peak in the 2nd decade and more frequent occurrence (in 60%) in the male sex. 4. Three stages of development can be distinguished in the pathogenesis of the mucus granulomas: an initial stage (interstitial mucus lakes), a resorption stage (mucus granulomas with macrophages, foam cells and foreign bodies giant cells) and a terminal stage with the development of a pseudocyst (capsule of collagen tissue, no epithelial demarcation). 5. The retention mucocele (synonym: mucus retention cyst) is a rare type of mucocele (33 cases = 11.3%). The main signs are: nearly equal occurrence in all oral regions, age peak in the 8th decade, moderate predominance of the female sex. 6. The retention mucoceles contain viscous mucous material, possess always an epithelial demarcation of the cysts differentiated analogous to the different segments of the salivary duct system and show as a rule no inflammatory reaction compared with the extravasation mucoceles. 7. Microtraumas and mucus congestions play the important role in the development of the extravasation mucocele. The final formation depends on the amount of the overflowed mucus and the intensity of the mucus phagocytosis. 8

  11. Simvastatin Inhibits Airway Hyperreactivity

    PubMed Central

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

    2009-01-01

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

  12. Novel Roles for Chloride Channels, Exchangers, and Regulators in Chronic Inflammatory Airway Diseases

    PubMed Central

    Sala-Rabanal, Monica; Yurtsever, Zeynep; Berry, Kayla N.; Brett, Tom J.

    2015-01-01

    Chloride transport proteins play critical roles in inflammatory airway diseases, contributing to the detrimental aspects of mucus overproduction, mucus secretion, and airway constriction. However, they also play crucial roles in contributing to the innate immune properties of mucus and mucociliary clearance. In this review, we focus on the emerging novel roles for a chloride channel regulator (CLCA1), a calcium-activated chloride channel (TMEM16A), and two chloride exchangers (SLC26A4/pendrin and SLC26A9) in chronic inflammatory airway diseases. PMID:26612971

  13. Recurrent respiratory infections in a child with fucosidosis: is the mucus too thin for effective transport?

    PubMed

    Rubin, B K; MacLeod, P M; Sturgess, J; King, M

    1991-01-01

    Fucosidosis is caused by a deficiency of the lysosomal enzyme alpha-L-fucosidase (ALF) leading to an accumulation of glycoproteins in a variety of cells. Infants and young children with this disorder are prone to recurrent sinus and pulmonary infections and often die of pneumonia. We studied the mucociliary and systemic immune function in a 6 year old girl with fucosidosis and recurrent respiratory infections. All measurements of systemic immune function were normal. Sweat chloride was normal when measured on angiokeratotic skin but was greater than 65 mg/L on uninvolved areas. During the placement of tympanic ventilation tubes, tracheal mucus was gently aspirated and a mucosal biopsy was taken. Tracheal mucus transport was not measured. The biopsy material was examined under phase contrast microscopy and revealed ciliated cells with apparently normal beating. TEM of these cells showed a characteristic pattern of vacuoles in the cytoplasm as described in other tissues from patients with fucosidosis. Ciliary ultrastructure was normal. Mucus viscoelasticity was measured in a magnetic microrheometer. The loss tangent was 2 SD above the mean for normal mucus and mechanical impedance was about 2 SD below the mean. These changes are similar in direction but double in magnitude to what has been described with methacholine administration in dogs. The high compliance of the mucus may be due to incomplete assembly of mucus glycoprotein or to decreased secretion of glycoproteins in respiratory secretions. This leads to mucus that is abnormally watery and thus difficult to clear from the airway. PMID:1896242

  14. Scalable Method to Produce Biodegradable Nanoparticles that Rapidly Penetrate Human Mucus

    PubMed Central

    Xu, Qingguo; Boylan, Nicholas J.; Cai, Shutian; Miao, Bolong; Patel, Himatkumar; Hanes, Justin

    2013-01-01

    Mucus typically traps and rapidly removes foreign particles from the airways, gastrointestinal tract, nasopharynx, female reproductive tract and the surface of the eye. Nanoparticles capable of rapid penetration through mucus can potentially avoid rapid clearance, and open significant opportunities for controlled drug delivery at mucosal surfaces. Here, we report an industrially scalable emulsification method to produce biodegradable mucus-penetrating particles (MPP). The emulsification of diblock copolymers of poly(lactic-co-glycolic acid) and polyethylene glycol (PLGA-PEG) using low molecular weight (MW) emulsifiers forms dense brush PEG coatings on nanoparticles that allow rapid nanoparticle penetration through fresh undiluted human mucus. In comparison, conventional high MW emulsifiers, such as polyvinyl alcohol (PVA), interrupts the PEG coating on nanoparticles, resulting in their immobilization in mucus owing to adhesive interactions with mucus mesh elements. PLGA-PEG nanoparticles with a wide range of PEG MW (1, 2, 5, and 10 kDa), prepared by the emulsification method using low MW emulsifiers, all rapidly penetrated mucus. A range of drugs, from hydrophobic small molecules to hydrohilic large biologics, can be efficiently loaded into biodegradable MPP using the method described. This readily scalable method should facilitate the production of MPP products for mucosal drug delivery, as well as potentially longer-circulating particles following intravenous administration. PMID:23751567

  15. Management of the artificial airway.

    PubMed

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

    2014-06-01

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

  16. Tachykinin receptors and airway pathophysiology.

    PubMed

    Maggi, C A

    1993-05-01

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

  17. Roflumilast combined with adenosine increases mucosal hydration in human airway epithelial cultures after cigarette smoke exposure

    PubMed Central

    Tyrrell, Jean; Qian, Xiaozhong; Freire, Jose

    2015-01-01

    Chronic obstructive pulmonary disease (COPD) is a growing cause of morbidity and mortality worldwide. Recent studies have shown that cigarette smoke (CS) induces cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction, which leads to airway-surface liquid (ASL) dehydration. This in turn contributes to the mucus dehydration and impaired mucociliary clearance that are seen in the chronic bronchitis form of COPD. Roflumilast is a phosphodiesterase 4 inhibitor that may improve lung function and reduce the frequency of exacerbations in patients with COPD. Although roflumilast can affect cAMP metabolism, little is known about the downstream pharmacological effects in the airways. We hypothesized that roflumilast would increase ASL rehydration in human bronchial epithelial cultures (HBECs) after chronic CS exposure. cAMP production was measured by Förster resonance energy transfer in HEK293T cells and by ELISA in HBECs. ASL height was measured by xz-confocal microscopy after air exposure or following HBEC exposure to freshly produced CS. Roflumilast had little effect on cAMP or ASL height when applied on its own; however, roflumilast significantly potentiated adenosine-induced increases in cAMP and ASL height in CS-exposed HBECs. Roflumilast increased the rate of ASL height recovery in cultures after CS exposure compared with controls. In contrast, the β2-adrenergic receptor agonists isoproterenol and salmeterol failed to increase ASL height after CS exposure. Our data suggest that roflumilast can increase ASL hydration in CS-exposed HBECs, which is predicted to be beneficial for the treatment of mucus dehydration/mucus stasis in patients with COPD chronic bronchitis. PMID:25795727

  18. Roflumilast combined with adenosine increases mucosal hydration in human airway epithelial cultures after cigarette smoke exposure.

    PubMed

    Tyrrell, Jean; Qian, Xiaozhong; Freire, Jose; Tarran, Robert

    2015-05-15

    Chronic obstructive pulmonary disease (COPD) is a growing cause of morbidity and mortality worldwide. Recent studies have shown that cigarette smoke (CS) induces cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction, which leads to airway-surface liquid (ASL) dehydration. This in turn contributes to the mucus dehydration and impaired mucociliary clearance that are seen in the chronic bronchitis form of COPD. Roflumilast is a phosphodiesterase 4 inhibitor that may improve lung function and reduce the frequency of exacerbations in patients with COPD. Although roflumilast can affect cAMP metabolism, little is known about the downstream pharmacological effects in the airways. We hypothesized that roflumilast would increase ASL rehydration in human bronchial epithelial cultures (HBECs) after chronic CS exposure. cAMP production was measured by Förster resonance energy transfer in HEK293T cells and by ELISA in HBECs. ASL height was measured by xz-confocal microscopy after air exposure or following HBEC exposure to freshly produced CS. Roflumilast had little effect on cAMP or ASL height when applied on its own; however, roflumilast significantly potentiated adenosine-induced increases in cAMP and ASL height in CS-exposed HBECs. Roflumilast increased the rate of ASL height recovery in cultures after CS exposure compared with controls. In contrast, the β2-adrenergic receptor agonists isoproterenol and salmeterol failed to increase ASL height after CS exposure. Our data suggest that roflumilast can increase ASL hydration in CS-exposed HBECs, which is predicted to be beneficial for the treatment of mucus dehydration/mucus stasis in patients with COPD chronic bronchitis. PMID:25795727

  19. A new paradigm in respiratory hygiene: modulating respiratory secretions to contain cough bioaerosol without affecting mucus clearance

    PubMed Central

    Zayas, Gustavo; Valle, Juan C; Alonso, Mauricio; Alfaro, Henry; Vega, Daniel; Bonilla, Gloria; Reyes, Miguel; King, Malcolm

    2007-01-01

    Background Several strategies and devices have been designed to protect health care providers from acquiring transmissible respiratory diseases while providing care. In modulating the physical characteristics of the respiratory secretions to minimize the aerosolization that facilitates transmission of airborne diseases, a fundamental premise is that the prototype drugs have no adverse effect on the first line of respiratory defense, clearance of mucus by ciliary action. Methods To assess and demonstrate the primary mechanism of our mucomodulators (XLs), we have built our evidence moving from basic laboratory studies to an ex-vivo model and then to an in-vivo large animal model. We exposed anesthetized dogs without hypersecretion to different dose concentrations of aerosolized XL "B", XL "D" and XL "S". We assessed: cardio-respiratory pattern, tracheal mucus clearance, airway patency, and mucus viscoelastic changes. Results Exposure of frog palate mucus to XLs did not affect the clearance of mucus by ciliary action. Dogs maintained normal cardio-respiratory pattern with XL administration. Tracheal mucociliary clearance in anesthetized dogs indicated a sustained 40% mean increase. Tracheal mucus showed increased filance, and there was no mucus retention in the airways. Conclusion The ex-vivo frog palate and the in-vivo mammalian models used in this study, appear to be appropriate and complement each other to better assess the effects that our mucomodulators exert on the mucociliary clearance defence mechanism. The physiological function of the mucociliary apparatus was not negatively affected in any of the two epithelial models. Airway mucus crosslinked by mucomodulators is better cleared from an intact airway and normally functioning respiratory system, either due to enhanced interaction with cilia or airflow-dependent mechanisms. Data obtained in this study allow us to assure that we have complied with the fundamental requirement criteria established in the initial

  20. How does serum brain natriuretic peptide level change under nasal continuous positive airway pressure in obstructive sleep apnea-hypopnea syndrome?

    PubMed Central

    Msaad, Sameh; Marrakchi, Rim; Grati, Malek; Gargouri, Rahma; Kammoun, Samy; Jammoussi, Kamel; Yangui, Ilhem

    2016-01-01

    Background Obstructive sleep apnea-hypopnea syndrome (OSAHS) is associated with cardiovascular morbidity and mortality, which can be improved by using continuous positive airway pressure (CPAP) therapy. However, the pathophysiological links between the two kinds of disease and the mechanism of the CPAP effect remain incompletely understood. We aimed to inquire into the myocardial involvement in this relationship. We suggested that serum brain natriuretic peptide (BNP) is sensitive enough to detect myocardial stress caused by OSAHS. Design and methods Sixty-four subjects without cardiovascular disease (21 controls, 24 normotensive OSAHS patients, and 19 hypertensive OSAHS patients) were analyzed for serum BNP at baseline and serially over 6 months. CPAP was applied to 23 patients with severe OSAHS. Results At baseline, the serum BNP levels were significantly higher (p=0.0001) in the OSAHS group (22.3±14.79 pg/ml) than in the control group (9.2±6.75 pg/ml). Increased serum BNP levels were significantly associated with mean transcutaneous oxygen saturation (SpO2) (p<0.0001), minimal SpO2 (p=0.002), oxygen desaturation index (p=0.001), and total sleep time spent with SpO2 lower than 90% (p=0.002). All patients with elevated BNP levels (≥37 pg/ml) had moderate or severe OSAHS (11/43 OSAHS patients). The more severe the OSAHS, the higher the BNP levels were. However, only the difference between severe and mild OSAHS was statistically significant (p=0.029). Hypertensive OSAHS patients had the highest baseline BNP levels (27.7±16.74 pg/ml). They were significantly higher (p=0.001) than in normotensive OSAHS patients (18±11.72 pg/ml) (p=0.039) and the controls (9.2±6.75 pg/ml). As compared with baseline, treatment with CPAP significantly decreased BNP levels in both hypertensive and normotensive OSAHS patients (respectively, from 36±16.10 to 29.7±14.29 pg/ml, p<0.001, and from 20±10.09 to 16±8.98 pg/ml, p<0.001). In contrast, the BNP levels slightly increased in

  1. Mathematical modeling of molecular diffusion through mucus

    PubMed Central

    Cu, Yen; Saltzman, W. Mark

    2008-01-01

    The rate of molecular transport through the mucus gel can be an important determinant of efficacy for therapeutic agents delivered by oral, intranasal, intravaginal/rectal, and intraocular routes. Transport through mucus can be described by mathematical models based on principles of physical chemistry and known characteristics of the mucus gel, its constituents, and of the drug itself. In this paper, we review mathematical models of molecular diffusion in mucus, as well as the techniques commonly used to measure diffusion of solutes in the mucus gel, mucus gel mimics, and mucosal epithelia. PMID:19135488

  2. Liquid crystalline order in mucus

    NASA Technical Reports Server (NTRS)

    Viney, C.; Huber, A. E.; Verdugo, P.

    1993-01-01

    Mucus plays an exceptionally wide range of important biological roles. It operates as a protective, exchange, and transport medium in the digestive, respiratory, and reproductive systems of humans and other vertebrates. Mucus is a polymer hydrogel. It is secreted as discrete packages (secretory granules) by specialized secretory cells. Mucus hydrogel is stored in a condensed state inside the secretory granules. Depending upon the architecture of their constituent macromolecules and on the composition of the solvent, polymer gels can form liquid crystalline microstructures, with orientational order being exhibited over optically resolvable distances. Individual mucin molecules consist of alternating rigid segments (heavily glycosylated; hydrophilic) and flexible segments (nonglycosylated; hydrophobic). Polymer molecules consisting of rigid units linked by flexible spacers are frequently associated with liquid crystalline behavior, which again raises the possibility that mucus could form anisotropic fluid phases. Suggestions that mucins may be self-associating in dilute solution have previously been challenged on the basis of sedimentation-equilibrium studies performed on mucus in which potential sites of association were competitively blocked with inhibitors. However, the formation of stable liquid crystalline phases does not depend on the existence of inter- or intramolecular associations; these phases can form on the basis of steric considerations alone.

  3. Total airway reconstruction.

    PubMed

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

    2013-02-01

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

  4. Diffusion-sensitive optical coherence tomography for real-time monitoring of mucus thinning treatments

    NASA Astrophysics Data System (ADS)

    Blackmon, Richard L.; Kreda, Silvia M.; Sears, Patrick R.; Ostrowski, Lawrence E.; Hill, David B.; Chapman, Brian S.; Tracy, Joseph B.; Oldenburg, Amy L.

    2016-03-01

    Mucus hydration (wt%) has become an increasingly useful metric in real-time assessment of respiratory health in diseases like cystic fibrosis and COPD, with higher wt% indicative of diseased states. However, available in vivo rheological techniques are lacking. Gold nanorods (GNRs) are attractive biological probes whose diffusion through tissue is sensitive to the correlation length of comprising biopolymers. Through employment of dynamic light scattering theory on OCT signals from GNRs, we find that weakly-constrained GNR diffusion predictably decreases with increasing wt% (more disease-like) mucus. Previously, we determined this method is robust against mucus transport on human bronchial epithelial (hBE) air-liquid interface cultures (R2=0.976). Here we introduce diffusion-sensitive OCT (DS-OCT), where we collect M-mode image ensembles, from which we derive depth- and temporally-resolved GNR diffusion rates. DS-OCT allows for real-time monitoring of changing GNR diffusion as a result of topically applied mucus-thinning agents, enabling monitoring of the dynamics of mucus hydration never before seen. Cultured human airway epithelial cells (Calu-3 cell) with a layer of endogenous mucus were doped with topically deposited GNRs (80x22nm), and subsequently treated with hypertonic saline (HS) or isotonic saline (IS). DS-OCT provided imaging of the mucus thinning response up to a depth of 600μm with 4.65μm resolution, over a total of 8 minutes in increments of >=3 seconds. For both IS and HS conditions, DS-OCT captured changes in the pattern of mucus hydration over time. DS-OCT opens a new window into understanding mechanisms of mucus thinning during treatment, enabling real-time efficacy feedback needed to optimize and tailor treatments for individual patients.

  5. The Epithelial Anion Transporter Pendrin Is Induced by Allergy and Rhinovirus Infection, Regulates Airway Surface Liquid, and Increases Airway Reactivity and Inflammation in an Asthma Model1

    PubMed Central

    Nakagami, Yasuhiro; Favoreto, Silvio; Zhen, Guohua; Park, Sung-Woo; Nguyenvu, Louis T.; Kuperman, Douglas A.; Dolganov, Gregory M.; Huang, Xiaozhu; Boushey, Homer A.; Avila, Pedro C.; Erle, David J.

    2008-01-01

    Asthma exacerbations can be triggered by viral infections or allergens. The Th2 cytokines IL-13 and IL-4 are produced during allergic responses and cause increases in airway epithelial cell mucus, electrolyte and water secretion into the airway surface liquid (ASL). Since ASL dehydration can cause airway inflammation and obstruction, ion transporters could play a role in pathogenesis of asthma exacerbations. We previously reported that expression of the epithelial cell anion transporter pendrin is markedly increased in response to IL-13. Here we show that pendrin plays a role in allergic airway disease and in regulation of ASL thickness. Pendrin-deficient mice had less allergen-induced airway hyperreactivity and inflammation than control mice although other aspects of the Th2 response were preserved. In cultures of IL-13-stimulated mouse tracheal epithelial cells, pendrin deficiency caused an increase in ASL thickness, suggesting that reductions in allergen-induced hyperreactivity and inflammation in pendrin-deficient mice result from improved ASL hydration. To determine whether pendrin might also play a role in virus-induced exacerbations of asthma, we measured pendrin mRNA expression in human subjects with naturally occurring common colds caused by rhinovirus and found a 4.9-fold-increase in mean expression during colds. Studies of cultured human bronchial epithelial cells indicated that this increase could be explained by the combined effects of rhinovirus and IFN-γ, a Th1 cytokine induced during virus infection. We conclude that pendrin regulates ASL thickness and may be an important contributor to asthma exacerbations induced by viral infections or allergens. PMID:18641360

  6. Comprehensive Airway Management of Patients with Maxillofacial Trauma

    PubMed Central

    Kellman, Robert M.; Losquadro, William D.

    2008-01-01

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

  7. Molecular Mechanisms of Airway Hyperresponsiveness in a Murine Model of Steroid-Resistant Airway Inflammation.

    PubMed

    Manni, Michelle L; Mandalapu, Sivanarayana; McHugh, Kevin J; Elloso, M Merle; Dudas, Paul L; Alcorn, John F

    2016-02-01

    IL-13 and IL-17A, produced mainly by Th2 and Th17 cells, respectively, have an influential role in asthma pathogenesis. We examined the role of IL-13 and IL-17A in mediating airway hyperresponsiveness (AHR), lung inflammation, and mucus metaplasia in a dual Th2/Th17 model of asthma. IL-13 and/or IL-17A were neutralized using mAbs. Th2/Th17 adoptive transfer induced a mixed asthma phenotype characterized by elevated eosinophilia and neutrophilia, tissue inflammation, mucus metaplasia, and AHR that were partially reversible with steroid treatment. Pulmonary inflammation and quasi-static lung compliance were largely unaffected by neutralization of IL-13 and/or IL-17A. However, neutralization of IL-13 alone or in combination with IL-17A significantly attenuated AHR and mucus metaplasia. Further, STAT6 activation was attenuated following IL-13 and IL-13/IL-17A Ab treatment. We next assessed the role of STAT6 in Th2/Th17-mediated allergic airway disease using STAT6(-/-) mice. STAT6(-/-) mice adoptively transferred with Th2/Th17 cells had decreased AHR compared with controls. These data suggest that IL-13 drives AHR and mucus metaplasia in a STAT6-dependent manner, without directly contributing to airway or tissue inflammation. IL-17A independently contributes to AHR, but it only partially mediates inflammation and mucus metaplasia in a mixed Th2/Th17 model of steroid-resistant asthma. PMID:26729801

  8. Enumerating viruses in coral mucus.

    PubMed

    Leruste, Amandine; Bouvier, Thierry; Bettarel, Yvan

    2012-09-01

    The distribution of viruses inhabiting the coral mucus remains undetermined, as there is no suitable standardized procedure for their separation from this organic matrix, principally owing to its viscosity and autofluorescence. Seven protocols were tested, and the most efficient separations were obtained from a chemical treatment requiring potassium citrate. PMID:22729548

  9. A pilot study investigating the effects of continuous positive airway pressure treatment and weight-loss surgery on autonomic activity in obese obstructive sleep apnea patients☆, ☆☆

    PubMed Central

    Bakker, Jessie P.; Campana, Lisa M.; Montesi, Sydney B.; Balachandran, Jayshankar; DeYoung, Pamela N.; Smales, Erik; Patel, Sanjay R.; Malhotra, Atul

    2015-01-01

    Background We have previously demonstrated that severity of obstructive sleep apnea (OSA) as measured by the apnea–hypopnea index (AHI) is a significant independent predictor of readily-computed time-domain metrics of short-term heart rate variability (HRV). Methods We aimed to assess time-domain HRV measured over 5-min while awake in a trial of obese subjects undergoing one of two OSA therapies: weight-loss surgery (n = 12, 2 males, median and interquartile range (IQR) for BMI 43.7 [42.0, 51.4] kg/m2, and AHI 18.1 [16.3, 67.5] events/h) or continuous positive airway pressure (CPAP) (n = 15, 11 males, median BMI 33.8 [31.3, 37.9] kg/m2, and AHI 36.5 [24.7, 77.3] events/h). Polysomnography was followed by electrocardiography during wakefulness; measurements were repeated at 6 and 12–18 months post-intervention. Results Despite similar measurements at baseline, subjects who underwent surgery exhibited greater improvement in short-term HRV than those who underwent CPAP (p = 0.04). Conclusions Our data suggest a possible divergence in autonomic function between the effects of weight loss resulting from bariatric surgery, and the amelioration of obstructive respiratory events resulting from CPAP treatment. Randomized studies are necessary before clinical recommendations can be made. PMID:24636793

  10. Chronic obstructive pulmonary disease.

    PubMed

    Barnes, Peter J; Burney, Peter G J; Silverman, Edwin K; Celli, Bartolome R; Vestbo, Jørgen; Wedzicha, Jadwiga A; Wouters, Emiel F M

    2015-01-01

    Chronic obstructive pulmonary disease (COPD) is a common disease with high global morbidity and mortality. COPD is characterized by poorly reversible airway obstruction, which is confirmed by spirometry, and includes obstruction of the small airways (chronic obstructive bronchiolitis) and emphysema, which lead to air trapping and shortness of breath in response to physical exertion. The most common risk factor for the development of COPD is cigarette smoking, but other environmental factors, such as exposure to indoor air pollutants - especially in developing countries - might influence COPD risk. Not all smokers develop COPD and the reasons for disease susceptibility in these individuals have not been fully elucidated. Although the mechanisms underlying COPD remain poorly understood, the disease is associated with chronic inflammation that is usually corticosteroid resistant. In addition, COPD involves accelerated ageing of the lungs and an abnormal repair mechanism that might be driven by oxidative stress. Acute exacerbations, which are mainly triggered by viral or bacterial infections, are important as they are linked to a poor prognosis. The mainstay of the management of stable disease is the use of inhaled long-acting bronchodilators, whereas corticosteroids are beneficial primarily in patients who have coexisting features of asthma, such as eosinophilic inflammation and more reversibility of airway obstruction. Apart from smoking cessation, no treatments reduce disease progression. More research is needed to better understand disease mechanisms and to develop new treatments that reduce disease activity and progression. PMID:27189863

  11. Measuring Nasal Obstruction.

    PubMed

    Keeler, Jarrod; Most, Sam P

    2016-08-01

    The nose and the nasal airway is highly complex with intricate 3-dimensional anatomy, with multiple functions in respiration and filtration of the respired air. Nasal airway obstruction (NAO) is a complex problem with no clearly defined "gold-standard" in measurement. There are 3 tools for the measurement of NAO: patient-derived measurements, physician-observed measurements, and objective measurements. We continue to work towards finding a link between subjective and objective nasal obstruction. The field of evaluation and surgical treatment for NAO has grown tremendously in the past 4-5 decades and will continue to grow as we learn more about the pathophysiology and treatment of nasal obstruction. PMID:27400845

  12. 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

  13. [Morphological changes in the respiratory organs in chronic obstructive pulmonary disease].

    PubMed

    Malykhin, F T; Kostornaya, I V

    2016-01-01

    The basis for airway remoldeling in patients with chronic obstructive pulmonary disease (COPD) is tissue changes contributing to thickening of the walls of the airway and its obstruction. As the disease becomes severer, there are increases in mucosal metaplasia, submucosal hypertrophy, peribronchial fibrosis, and airway smooth muscle mass. Drug therapy for COPD does not virtually lead to regression of airway obstruction, except when eosinophilia is present. PMID:27077144

  14. Mucus retention in heterotopic pancreas of the gastric antrum. A lesion mimicking mucinous carcinoma.

    PubMed

    Nopajaroonsri, C

    1994-09-01

    This report describes mucus retention developing in heterotopic pancreas of the gastric antrum. This unusual complication of heterotopic pancreas was seen in a 54-year-old black man who presented with postprandial nausea, vomiting, and weight loss. Gastroscopy revealed a 2-cm pyloric polyp, which was seen to intermittently obstruct the pylorus. Exploratory laparotomy confirmed an intramural mass in the antrum with serosal thickening and nodules. Frozen-section examination of the serosal nodule revealed a pool of mucus containing epithelial clusters and chronic inflammatory cells with no verifiable pancreatic tissue. These findings suggested the possibility of a mucinous carcinoma involving the serosa. Following gastrectomy, however, heterotopic pancreatic tissue was identified in the outer muscular propria extending to the mucosa of the antrum with no evidence of carcinoma. This heterotopic pancreatic tissue showed ductal obstruction and mucus retention. As a result, some ducts were ruptured and transformed into small nodules of mucus lakes with clusters of residual ductal epithelium. We therefore concluded that the mucous extravasation nodules on the antral serosa represented a benign lesion resulting from mucus retention in the heterotopic pancreas. In contrast to mucinous carcinoma, these benign mucous extravasation nodules were closely associated with the heterotopic pancreas, and showed significant inflammation and fibrosis but no overt epithelial anaplasia. The significance of the mucous extravasation nodule in the heterotopic pancreas is its potential confusion with mucinous carcinoma. PMID:8067516

  15. Chronic obstructive pulmonary disease: clinical integrative physiology.

    PubMed

    O'Donnell, Denis E; Laveneziana, Pierantonio; Webb, Katherine; Neder, J Alberto

    2014-03-01

    Peripheral airway dysfunction, inhomogeneous ventilation distribution, gas trapping, and impaired pulmonary gas exchange are variably present in all stages of chronic obstructive pulmonary disease (COPD). This article provides a cogent physiologic explanation for the relentless progression of activity-related dyspnea and exercise intolerance that all too commonly characterizes COPD. The spectrum of physiologic derangements that exist in smokers with mild airway obstruction and a history compatible with COPD is examined. Also explored are the perceptual and physiologic consequences of progressive erosion of the resting inspiratory capacity. Finally, emerging information on the role of cardiocirculatory impairment in contributing to exercise intolerance in patients with varying degrees of airway obstruction is reviewed. PMID:24507837

  16. Influenza A penetrates host mucus by cleaving sialic acids with neuraminidase

    PubMed Central

    2013-01-01

    Background Influenza A virus (IAV) neuraminidase (NA) cleaves sialic acids (Sias) from glycans. Inhibiting NA with oseltamivir suppresses both viral infection, and viral release from cultured human airway epithelial cells. The role of NA in viral exit is well established: it releases budding virions by cleaving Sias from glycoconjugates on infected cells and progeny virions. The role of NA in viral entry remains unclear. Host respiratory epithelia secrete a mucus layer rich in heavily sialylated glycoproteins; these could inhibit viral entry by mimicking sialylated receptors on the cell surface. It has been suggested that NA allows influenza to penetrate the mucus by cleaving these sialylated decoys, but the exact mechanism is not yet established. Methods We tested IAV interaction with secreted mucus using frozen human trachea/bronchus tissue sections, and bead-bound purified human salivary mucins (HSM) and purified porcine submaxillary mucins (PSM). The protective effect of mucus was analyzed using MDCK cells coated with purified HSM and PSM with known Sia content. Oseltamivir was used to inhibit NA activity, and the fluorescent reporter substrate, 4MU-Neu5Ac, was used to quantify NA activity. Results IAV binds to the secreted mucus layer of frozen human trachea/bronchus tissues in a Sia dependent manner. HSM inhibition of IAV infection is Sia dose-dependent, but PSM cannot inhibit infection of underlying cells. HSM competitively inhibits NA cleavage of 4MU-Neu5Ac, reporter substrate. Human IAV effectively cleaves Sias from HSM but not from PSM, and binds to HSM but not to PSM. Conclusion IAV interacts with human mucus on frozen tissue sections and mucus-coated beads. Inhibition of IAV infection by sialylated human mucus is dose-dependent, and enhanced when NA is inhibited with oseltamivir. Thus NA cleaves sialylated decoys during initial stages of infection. Understanding IAV interactions with host mucins is a promising new avenue for drug development. PMID

  17. A non-redundant role for mouse Serpinb3a in the induction of mucus production in asthma

    PubMed Central

    Sivaprasad, Umasundari; Askew, David J.; Ericksen, Mark B.; Gibson, Aaron M.; Stier, Matthew T.; Brandt, Eric; Bass, Stacey A.; Daines, Michael O.; Chakir, Jamila; Stringer, Keith F.; Wert, Susan E.; Whitsett, Jeffrey A.; Le Cras, Timothy D.; Wills-Karp, Marsha; Silverman, Gary A.; Khurana Hershey, Gurjit K.

    2010-01-01

    Background Asthma is a major public health burden worldwide. Studies from our group and others have demonstrated that SERPINB3 and B4 are induced in asthmatics; however their mechanistic role in asthma has yet to be determined. Objective To evaluate the role of Serpin3a, the murine homolog of human SERPINB3 and B4, in asthma. Methods We studied wild type Balb/c and Serpinb3a null mice in house dust mite or IL-13 induced asthma models and evaluated airway hyperresponsiveness, inflammation, and goblet cell hyperplasia. Results Airway hyperresponsiveness and goblet cell hyperplasia were markedly attenuated in the Serpinb3a null mice compared to the wild type mice following allergen challenge, with minimal effects on inflammation. Expression of SPDEF, a transcription factor that mediates goblet cell hyperplasia, was decreased in the absence of Serpinb3a. IL-13 treated Serpinb3a null mice showed attenuated AHR, inflammation, and mucus production. Conclusions Excessive mucus production and mucus plugging are key pathologic features of asthma, yet the mechanisms responsible for mucus production are not well understood. Our data reveal a novel non-redundant role for Serpinb3a in mediating mucus production through regulation of SPDEF expression. This pathway may be used to effectively target mucus hypersecretion. PMID:21126757

  18. Upper airway resistance syndrome.

    PubMed

    Hasan, N; Fletcher, E C

    1998-07-01

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

  19. 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 ...

  20. 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

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

    PubMed

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

    2005-09-01

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

  2. Techniques to Bring Up Mucus

    MedlinePlus

    ... Bowler, MD, PhD (June 01, 2009) People with chronic obstructive pulmonary disease (COPD) and chronic bronchitis often produce a large amount ... an Appointment View all (43) doctors specializing in Chronic Obstructive Pulmonary Disease (COPD) Find a Doctor Clinical Trials For more ...

  3. Evaluation of short-term use of nocturnal nasal continuous positive airway pressure for a clinical profile and exercise capacity in adult patients with obstructive sleep apnea-hypopnea syndrome

    PubMed Central

    Goel, Amrit K; Talwar, Deepak; Jain, Sushil K

    2015-01-01

    Background and Aim: The obstructive sleep apnea–hypopnea syndrome (OSAHS) is a common chronic respiratory disease, characterized by repetitive complete or partial collapse of the upper airway during sleep. The clinical spectrum extends between stoppage of breathing, snoring, daytime somnolence, and fatigue, to serious cardiovascular disease, stroke, metabolic syndrome, increased morbidity, and mortality. We aim to evaluate the short-term use of nasal continuous positive airway pressure (nCPAP) therapy for the clinical profile and exercise capacity of patients with OSAHS. Patient Selection: Twenty patients diagnosed with moderate-to-severe OSAHS were enrolled in the study (study group — 15; clinically and PSG-matched control group — 5). Materials and Methods: Each patient was clinically evaluated for sleep-related symptoms, and also assessed with spirometry, the six-minute walk test (6MWT), and a symptom-limited incremental cardiopulmonary exercise test (CPET). The study group patients were administered nCPAP therapy for eight hours each night for four weeks, while the control group patients were just observed. They were re-assessed after four weeks and the data were statistically analyzed between the two groups. Results: The study group patients showed a significant (P- < 0.05) improvement in the OSAHS symptoms—the Epworth sleepiness score, six-minute walk distance; duration of exercise, power output, peak oxygen uptake, anaerobic threshold, diastolic blood pressure, dyspnea, and fatigue—in comparison with the control group patients. The improvement in exercise capacity following nCPAP therapy was attributed to the relief of disabling the OSAHS symptoms and improved cardiovascular, ventilator, and musculoskeletal functions. Conclusion: All OSAHS patients must be treated with nCPAP. PMID:25983407

  4. A Pilot Study on the Efficacy of Continuous Positive Airway Pressure on the Manifestations of Ménière's Disease in Patients with Concomitant Obstructive Sleep Apnea Syndrome

    PubMed Central

    Nakayama, Meiho; Masuda, Ayako; Ando, Kayoko Bhardwaj; Arima, Sachie; Kabaya, Kayoko; Inagaki, Akira; Nakamura, Yoshihisa; Suzuki, Motohiko; Brodie, Hilary; Diaz, Rodney C.; Murakami, Shingo

    2015-01-01

    Objective: To evaluate the effect of continuous positive airway pressure (CPAP) therapy on Ménière's disease patients with concomitant obstructive sleep apnea syndrome (OSAS), since recent reports suggest OSAS may cause dysfunction of the vestibular system. Study Design: Prospective study using CPAP administered to patients diagnosed with “Definite Ménière's disease” according to the guidelines of the American Academy of Otolaryngology— Head and Neck Surgery and combined with OSAS. Setting: University hospital. Methods: Twenty consecutive patients, 14 male and 6 female with active, unilateral, cochleovestibular Ménière's disease refractory to medical management who also had concurrent OSAS as defined by International Classification of Sleep Disorders, Second Edition were selected to undergo solitary CPAP therapy. Audiometric testing, caloric testing, and DHI survey were conducted before and after CPAP therapy and compared to assess effectiveness of CPAP therapy as utilized for treatment of Ménière's disease. Results: Although caloric testing did not show significant difference, audiometric testing and results of dizziness handicap inventory were significantly improved (p < 0.05) after CPAP therapy only, without standard treatment for Ménière's disease. Conclusions: Recent reports have suggested that OSAS may cause dysfunction of the vestibular system. We investigated whether standard therapy for OSAS would be of benefit in the management of vertigo and hearing loss in Ménière's disease patients. Our study cohort demonstrated significant improvement in both DHI and audiometric testing following solitary CPAP therapy for OSAS. Solitary CPAP therapy may become a new effective treatment strategy for Ménière's disease patients with OSAS, not just only for control of dizziness and vertigo but also for potential benefit of hearing. Citation: Nakayama M, Masuda A, Ando KB, Arima S, Kabaya K, Inagaki A, Nakamura Y, Suzuki M, Brodie H, Diaz RC, Murakami S

  5. Chronic obstructive pulmonary disease - adults - discharge

    MedlinePlus

    ... visit when they're all better. Save Your Energy at Home Place items you use often in ... or the skin around your fingernails are blue Alternative Names COPD - adults - discharge; Chronic obstructive airways disease - ...

  6. Clinical assessment and C-reactive protein (CRP), haptoglobin (Hp), and cardiac troponin I (cTnI) values of brachycephalic dogs with upper airway obstruction before and after surgery

    PubMed Central

    Planellas, Marta; Cuenca, Rafaela; Tabar, Maria-Dolores; Bertolani, Coralie; Poncet, Cyrill; Closa, Josep M.; Lorente, Juan; Cerón, José J.; Pastor, Josep

    2015-01-01

    Brachycephalic dogs have unique upper respiratory anatomy with abnormal breathing patterns that are similar to those in humans with obstructive sleep apnea syndrome (OSAS). The objectives of this multicenter prospective study were to assess the effects of surgical correction on clinical signs in dogs with brachycephalic airway obstructive syndrome (BAOS) and to evaluate the levels of several biomarkers [C-reactive protein (CRP); haptoglobin (Hp), and cardiac troponin I (cTnI)] used to determine systemic inflammation and myocardial damage. This study was conducted on 33 dogs with BAOS that were evaluated before and 1 to 2 mo after surgical correction. Palatoplasty was carried out by means of 2 different surgical techniques: carbon dioxide (CO2) laser (n = 12) and electrical scalpel (n = 21). Biomarker levels (CRP, Hp, and cTnI) were determined before and after surgery. There was a significant reduction in respiratory and gastrointestinal signs in dogs with BAOS after surgical treatment (P < 0.001). A greater reduction in respiratory signs (P < 0.002) was obtained using the CO2 laser. No statistical differences were found between CRP and cTnI levels, either before or after surgical correction. Haptoglobin concentration did increase significantly in the postsurgical period (P < 0.008). Surgical treatment in dogs with BAOS reduces clinical signs, regardless of the anatomical components present. Surgical treatment for BAOS is not useful to reduce CRP and Hp levels, probably because BAOS does not induce as obvious an inflammatory process in dogs as in human patients with OSAS. No reduction in cTnI levels was observed 1 mo after surgery in dogs with BAOS, which suggests that some degree of myocardial damage remains. PMID:25673910

  7. Clinical assessment and C-reactive protein (CRP), haptoglobin (Hp), and cardiac troponin I (cTnI) values of brachycephalic dogs with upper airway obstruction before and after surgery.

    PubMed

    Planellas, Marta; Cuenca, Rafaela; Tabar, Maria-Dolores; Bertolani, Coralie; Poncet, Cyrill; Closa, Josep M; Lorente, Juan; Cerón, José J; Pastor, Josep

    2015-01-01

    Brachycephalic dogs have unique upper respiratory anatomy with abnormal breathing patterns that are similar to those in humans with obstructive sleep apnea syndrome (OSAS). The objectives of this multicenter prospective study were to assess the effects of surgical correction on clinical signs in dogs with brachycephalic airway obstructive syndrome (BAOS) and to evaluate the levels of several biomarkers [C-reactive protein (CRP); haptoglobin (Hp), and cardiac troponin I (cTnI)] used to determine systemic inflammation and myocardial damage. This study was conducted on 33 dogs with BAOS that were evaluated before and 1 to 2 mo after surgical correction. Palatoplasty was carried out by means of 2 different surgical techniques: carbon dioxide (CO2) laser (n = 12) and electrical scalpel (n = 21). Biomarker levels (CRP, Hp, and cTnI) were determined before and after surgery. There was a significant reduction in respiratory and gastrointestinal signs in dogs with BAOS after surgical treatment (P < 0.001). A greater reduction in respiratory signs (P < 0.002) was obtained using the CO2 laser. No statistical differences were found between CRP and cTnI levels, either before or after surgical correction. Haptoglobin concentration did increase significantly in the postsurgical period (P < 0.008). Surgical treatment in dogs with BAOS reduces clinical signs, regardless of the anatomical components present. Surgical treatment for BAOS is not useful