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Mechanism of airway clearance

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https://www.readbyqxmd.com/read/28077104/effects-of-treadmill-exercise-versus-flutter%C3%A2-on-respiratory-flow-and-sputum-properties-in-adults-with-cystic-fibrosis-a-randomised-controlled-cross-over-trial
#1
Tiffany J Dwyer, Rahizan Zainuldin, Evangelia Daviskas, Peter T P Bye, Jennifer A Alison
BACKGROUND: Treadmill exercise and airway clearance with the Flutter® device have previously been shown to improve mucus clearance mechanisms in people with cystic fibrosis (CF) but have not been compared. It is therefore not known if treadmill exercise is an adequate form of airway clearance that could replace established airway clearance techniques, such as the Flutter®. The aim of this study was to evaluate respiratory flow, sputum properties and subjective responses of treadmill exercise and Flutter® therapy, compared to resting breathing (control)...
January 11, 2017: BMC Pulmonary Medicine
https://www.readbyqxmd.com/read/28062701/widespread-virus-replication-in-alveoli-drives-acute-respiratory-distress-syndrome-in-aerosolized-h5n1-influenza-infection-of-macaques
#2
Elizabeth R Wonderlich, Zachary D Swan, Stephanie J Bissel, Amy L Hartman, Jonathan P Carney, Katherine J O'Malley, Adebimpe O Obadan, Jefferson Santos, Reagan Walker, Timothy J Sturgeon, Lonnie J Frye, Pauline Maiello, Charles A Scanga, Jennifer D Bowling, Anthea L Bouwer, Parichat A Duangkhae, Clayton A Wiley, JoAnne L Flynn, Jieru Wang, Kelly S Cole, Daniel R Perez, Douglas S Reed, Simon M Barratt-Boyes
Human infections with highly pathogenic avian influenza A (H5N1) virus are frequently fatal but the mechanisms of disease remain ill-defined. H5N1 infection is associated with intense production of proinflammatory cytokines, but whether this cytokine storm is the main cause of fatality or is a consequence of extensive virus replication that itself drives disease remains controversial. Conventional intratracheal inoculation of a liquid suspension of H5N1 influenza virus in nonhuman primates likely results in efficient clearance of virus within the upper respiratory tract and rarely produces severe disease...
January 6, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28062487/alcohol-drives-s-nitrosylation-and-redox-activation-of-protein-phosphatase-1-causing-bovine-airway-cilia-dysfunction
#3
Michael Earl Price, Jacqueline A Pavlik, Miao Liu, Shi-Jian Ding, Todd A Wyatt, Joseph H Sisson
Individuals with alcohol (ethanol) use disorders are at increased risk for lung infections in part due to defective mucociliary clearance driven by motile cilia in the airways. We recently reported that isolated demembranated bovine cilia (axonemes) are capable of producing nitric oxide (∙NO) when exposed to biologically relevant concentrations of alcohol. This increased presence of ∙NO can lead to protein S-nitrosylation, a posttranslational modification signaling mechanism involving reversible adduction of nitrosium cations or ⋅NO to thiolate or thiyl groups, respectively, of proteins forming S-nitrosothiols...
January 6, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28060951/hiv-infects-bronchial-epithelium-and-suppresses-components-of-the-mucociliary-clearance-apparatus
#4
S Chinnapaiyan, T Parira, R Dutta, M Agudelo, A Morris, M Nair, H J Unwalla
Recurrent lung infections and pneumonia are emerging as significant comorbidities in the HIV-infected population in the era of combination antiretroviral therapy (cART). HIV infection has been reported to suppress nasal mucociliary clearance (MCC). Since the primary components driving nasal MCC and bronchial MCC are identical, it is possible that bronchial MCC is affected as well. Effective MCC requires optimal ciliary beating which depends on the maintenance of the airway surface liquid (ASL), a function of cystic fibrosis transmembrane conductance regulator (CFTR) activity and the integrity of the signaling mechanism that regulates ciliary beating and fluid secretion...
2017: PloS One
https://www.readbyqxmd.com/read/28043871/bcl-2-inhibitors-reduce-steroid-insensitive-airway-inflammation
#5
Bao-Ping Tian, Li-Xia Xia, Zheng-Qiang Bao, Hao Zhang, Zhi-Wei Xu, Yuan-Yuan Mao, Chao Cao, Luan-Qing Che, Jin-Kai Liu, Wen Li, Zhi-Hua Chen, Songmin Ying, Hua-Hao Shen
BACKGROUND: Asthmatic inflammation is dominated either by eosinophil and/or neutrophil accumulation in airways. Disposal of these inflammatory cells is the key to disease control. Eosinophilic airway inflammation is responsive to corticosteroid treatment, while neutrophilic inflammation is resistant and increases the burden of global health care. Corticosteroid resistant neutrophilic asthma remains mechanistically poorly understood and requires novel effective therapeutic strategies. OBJECTIVE: We thought to explore the underlying mechanisms of airway inflammation persistence as well as corticosteroid resistance, and to investigate a new strategy of effective treatment against corticosteroid-insensitive neutrophilic asthma...
December 30, 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28025644/tnf%C3%AE-affects-ciliary-beat-response-to-increased-viscosity-in-human-pediatric-airway-epithelium
#6
Claudia González, Karla Droguett, Mariana Rios, Noam A Cohen, Manuel Villalón
In airway epithelium, mucociliary clearance (MCC) velocity depends on the ciliary beat frequency (CBF), and it is affected by mucus viscoelastic properties. Local inflammation induces secretion of cytokines (TNFα) that can alter mucus viscosity; however airway ciliated cells have an autoregulatory mechanism to prevent the collapse of CBF in response to increase in mucus viscosity, mechanism that is associated with an increment in intracellular Ca(+2) level ([Ca(2+)]i). We studied the effect of TNFα on the autoregulatory mechanism that regulates CBF in response to increased viscosity using dextran solutions, in ciliated cells cultured from human pediatric epithelial adenoid tissue...
2016: BioMed Research International
https://www.readbyqxmd.com/read/28000620/aerobic-exercise-in-polluted-urban-environments-effects-on-airway-defense-mechanisms-in-young-healthy-amateur-runners
#7
Matheus Cavalcante de Sá, Naomi Kondo Nakagawa, Carmen Diva Saldiva de André, Regiani Carvalho-Oliveira, Tômas de Santana Carvalho, Marina Lazzari Nicola, Paulo Afonso de André, Paulo Hilario Nascimento Saldiva, Mauro Vaisberg
In this study, the effects of aerobic exercise on the upper airways and their defense mechanisms were investigated in athletes. The athletes ran in two different environments: the downtown streets of the city of São Paulo (Street), more polluted, and an urban forest (Forest), less polluted. Thirty-eight young healthy athletes ran for 45 min d(-1) randomly during five consecutive days, with an interval of 48 h before changing environment. Clinical parameters and respiratory tract defense markers were evaluated before and after the first run on Mondays (1 d) and on Fridays (5 d)...
December 21, 2016: Journal of Breath Research
https://www.readbyqxmd.com/read/27986442/world-trade-center-wtc-dust-exposure-in-mice-is-associated-with-inflammation-oxidative-stress-and-epigenetic-changes-in-the-lung
#8
Vasanthi R Sunil, Kinal N Vayas, Mingzhu Fang, Helmut Zarbl, Christopher Massa, Andrew J Gow, Jessica A Cervelli, Howard Kipen, Robert J Laumbach, Paul J Lioy, Jeffrey D Laskin, Debra L Laskin
Exposure to World Trade Center (WTC) dust has been linked to respiratory disease in humans. In the present studies we developed a rodent model of WTC dust exposure to analyze lung oxidative stress and inflammation, with the goal of elucidating potential epigenetic mechanisms underlying these responses. Exposure of mice to WTC dust (20μg, i.t.) was associated with upregulation of heme oxygenase-1 and cyclooxygenase-2 within 3days, a response which persisted for at least 21days. Whereas matrix metalloproteinase was upregulated 7days post-WTC dust exposure, IL-6RA1 was increased at 21days; conversely, expression of mannose receptor, a scavenger receptor important in particle clearance, decreased...
December 13, 2016: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/27930725/avertin%C3%A2-but-not-volatile-anesthetics-addressing-the-two-pore-domain-k-channel-task-1-slows-down-cilia-driven-particle-transport-in-the-mouse-trachea
#9
Ghulam Murtaza, Petra Mermer, Uwe Pfeil, Wolfgang Kummer
RATIONALE: Volatile anesthetics inhibit mucociliary clearance in the airways. The two-pore domain K+ channel, TASK-1, represents one of their molecular targets in that they increase its open probability. Here, we determine whether particle transport speed (PTS) at the mucosal surface of the mouse trachea, an important factor of the cilia-driven mechanism in mucociliary clearance, is regulated by TASK-1. METHODOLOGY/RESULTS: RT-PCR analysis revealed expression of TASK-1 mRNA in the manually dissected and laser-assisted microdissected tracheal epithelium of the mouse...
2016: PloS One
https://www.readbyqxmd.com/read/27870227/aspergillosis-and-the-role-of-mucins-in-cystic-fibrosis
#10
REVIEW
Abigail C Cowley, David J Thornton, David W Denning, Alexander Horsley
The prevalence of aspergillosis in CF patients has until recently been underestimated, but increasing evidence suggests that it may play an important role in the progression of CF lung disease. In healthy airways, Aspergillus fumigatus can be efficiently removed from the lung by mechanisms such as mucociliary clearance and cough. However, these mechanisms are defective in CF, allowing pathogens such as A. fumigatus to germinate and establish chronic infections within the airways. The precise means by which A...
November 21, 2016: Pediatric Pulmonology
https://www.readbyqxmd.com/read/27865862/impaired-mucus-clearance-exacerbates-allergen-induced-type-2-airway-inflammation-in-juvenile-mice
#11
Benedikt Fritzsching, Matthias Hagner, Lu Dai, Sandra Christochowitz, Raman Agrawal, Charlotte van Bodegom, Simone Schmidt, Jolanthe Schatterny, Stephanie Hirtz, Ryan Brown, Michelle Goritzka, Julia Duerr, Zhe Zhou-Suckow, Marcus A Mall
BACKGROUND: Type 2 airway inflammation plays a central role in the pathogenesis of allergen-induced asthma, but the underlying mechanisms remain poorly understood. Recently, we demonstrated that reduced mucociliary clearance, a characteristic feature of asthma, produces spontaneous type 2 airway inflammation in juvenile β-epithelial Na(+) channel (Scnn1b)-transgenic (Tg) mice. OBJECTIVE: We sought to determine the role of impaired mucus clearance in the pathogenesis of allergen-induced type 2 airway inflammation and identify cellular sources of the signature cytokine IL-13...
November 16, 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27864314/cilia-and-mucociliary-clearance
#12
Ximena M Bustamante-Marin, Lawrence E Ostrowski
Mucociliary clearance (MCC) is the primary innate defense mechanism of the lung. The functional components are the protective mucous layer, the airway surface liquid layer, and the cilia on the surface of ciliated cells. The cilia are specialized organelles that beat in metachronal waves to propel pathogens and inhaled particles trapped in the mucous layer out of the airways. In health this clearance mechanism is effective, but in patients with primary cilia dyskinesia (PCD) the cilia are abnormal, resulting in deficient MCC and chronic lung disease...
November 18, 2016: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/27863670/selection-and-fabrication-of-a-non-woven-polycarbonate-urethane-cover-for-a-tissue-engineered-airway-stent
#13
Weiluan Chen, Johanna Clauser, Anja Lena Thiebes, Donnacha J McGrath, Peter E McHugh, Ulrich Steinseifer, Stefan Jockenhoevel, Wim E Hennink, Robbert Jan Kok
One of the major problems in end-stage bronchotracheal cancer is stenosis of the upper airways, either due to luminal ingrowth of the tumor or mucus plugging. Airway stents that suppress tumor ingrowth and sustain mucociliary transport can alleviate these problems in end-stage bronchial cancer. We evaluated different types of polymeric covers for a tissue engineered airway stent. The distinguishing feature of this stent concept is that respiratory epithelial cells can grow on the luminal surface of the stent which facilitates mucociliary clearance...
November 30, 2016: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/27856789/collectins-h-ficolin-and-ll-37-reduce-influence-viral-replication-in-human-monocytes-and-modulate-virus-induced-cytokine-production
#14
Mitchell R White, Shweta Tripathi, Anamika Verma, Paul Kingma, Kazue Takahashi, Jens Jensenius, Steffen Thiel, Guangshun Wang, Erika C Crouch, Kevan L Hartshorn
Infiltrating activated monocytes are important mediators of damaging inflammation during influenza A virus (IAV) infection. We show that soluble respiratory proteins [collectins, surfactant proteins D (SP-D) and mannose binding lectin (MBL), H-ficolin and LL-37] inhibit replication of seasonal IAV in human monocytes. The collectins and H-ficolin also increased viral uptake by the cells, while LL-37 did not. H-ficolin was able to inhibit replication of the 2009 pandemic H1N1 strain (Cal09) in monocytes, but SP-D and LL-37 had significantly fewer inhibitory effects on this strain than on seasonal IAV...
November 17, 2016: Innate Immunity
https://www.readbyqxmd.com/read/27856714/nasal-high-flow-reduces-dead-space
#15
Winfried Möller, Sheng Feng, Ulrike Domanski, Karl-Josef Franke, Gülnaz Celik, Peter Bartenstein, Sven Becker, Gabriele Meyer, Otmar Schmid, Oliver Eickelberg, Stanislav Tatkov, Georg Nilius
Recent studies show that nasal high flow (NHF) therapy can support ventilation in patients with acute or chronic respiratory disorders. Clearance of dead-space has been suggested as being the key mechanisms of respiratory support with NHF therapy. The hypothesis of this study was that NHF in a dose-dependent manner can clear dead space of the upper airways from expired air and decrease re-breathing. The randomized cross-over study involved 10 volunteers using scintigraphy with (81m)Krypton-gas ((81m)Kr-gas) during a breath-holding maneuver with closed mouth and in three nasally breathing tracheotomized patients by volumetric capnography and oximetry through sampling CO2 and O2 in the trachea and measuring the inspired volume with inductance plethysmography following NHF rates of 15, 30 and 45 L/min...
November 17, 2016: Journal of Applied Physiology
https://www.readbyqxmd.com/read/27830759/marked-increases-in-mucociliary-clearance-produced-by-synergistic-secretory-agonists-or-inhibition-of-the-epithelial-sodium-channel
#16
Nam Soo Joo, Jin Hyeok Jeong, Hyung-Ju Cho, Jeffrey J Wine
Mucociliary clearance (MCC) is a critical host innate defense mechanism in airways, and it is impaired in cystic fibrosis (CF) and other obstructive lung diseases. Epithelial fluid secretion and absorption modify MCC velocity (MCCV). We tested the hypotheses that inhibiting fluid absorption accelerates MCCV, whereas inhibiting fluid secretion decelerates it. In airways, ENaC is mainly responsible for fluid absorption, while anion channels, including CFTR and Ca(2+)-activated chloride channels mediate anion/fluid secretion...
November 10, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27814452/water-permeability-adjusts-resorption-in-lung-epithelia-to-increased-apical-surface-liquid-volumes
#17
Hanna Schmidt, Christiane Michel, Peter Braubach, Michael Fauler, Daniel Neubauer, Kristin E Thompson, Manfred Frick, Boris Mizaikoff, Paul Dietl, Oliver H Wittekindt
The apical surface liquid layer (ASL) covers the airways and forms a first line of defense against pathogens. Maintenance of ASL volume by airway epithelia is essential for maintaining lung function. The proteolytic activation of epithelial Na(+) channels (ENaC) is believed to be the dominating mechanism to cope with increases in ASL volumes. Alternative mechanisms, in particular increases in epithelial water permeability (Posm), have so far been regarded as rather less important. However, most studies mainly addressed immediate effects upon apical volume expansion (AVE) and increases in ASL...
November 4, 2016: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/27794000/airway-epithelial-kif3a-regulates-th2-responses-to-aeroallergens
#18
Premkumar Vummidi Giridhar, Sheila M Bell, Anusha Sridharan, Priya Rajavelu, Joseph A Kitzmiller, Cheng-Lun Na, Matthew Kofron, Eric B Brandt, Mark Ericksen, Anjaparavanda P Naren, Changsuk Moon, Gurjit K Khurana Hershey, Jeffrey A Whitsett
KIF3A, the gene encoding kinesin family member 3A, is a susceptibility gene locus associated with asthma; however, mechanisms by which KIF3A might influence the pathogenesis of the disorder are unknown. In this study, we deleted the mouse Kif3a gene in airway epithelial cells. Both homozygous and heterozygous Kif3a gene-deleted mice were highly susceptible to aeroallergens from Aspergillus fumigatus and the house dust mite, resulting in an asthma-like pathology characterized by increased goblet cell metaplasia, airway hyperresponsiveness, and Th2-mediated inflammation...
December 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27788778/alcohol-and-lung-injury-and-immunity
#19
REVIEW
Samantha M Yeligar, Michael M Chen, Elizabeth J Kovacs, Joseph H Sisson, Ellen L Burnham, Lou Ann S Brown
Annually, excessive alcohol use accounts for more than $220 billion in economic costs and 80,000 deaths, making excessive alcohol use the third leading lifestyle-related cause of death in the US. Patients with an alcohol-use disorder (AUD) also have an increased susceptibility to respiratory pathogens and lung injury, including a 2-4-fold increased risk of acute respiratory distress syndrome (ARDS). This review investigates some of the potential mechanisms by which alcohol causes lung injury and impairs lung immunity...
September 2016: Alcohol
https://www.readbyqxmd.com/read/27773996/albuterol-improves-alveolar-capillary-membrane-conductance-in-healthy-humans
#20
Natalie E Taylor, Sarah E Baker, Thomas P Olson, Sophie Lalande, Bruce D Johnson, Eric M Snyder
BACKGROUND: Beta-2 adrenergic receptors (β2ARs) are located throughout the body including airway and alveolar cells. The β2ARs regulate lung fluid clearance through a variety of mechanisms including ion transport on alveolar cells and relaxation of the pulmonary lymphatics. We examined the effect of an inhaled β2-agonist (albuterol) on alveolar-capillary membrane conductance (DM) and pulmonary capillary blood volume (VC) in healthy humans. METHODS: We assessed the diffusing capacity of the lungs for carbon monoxide (DLCO) and nitric oxide (DLNO) at baseline, 30 minutes, and 60 minutes following nebulized albuterol (2...
2016: Clinical Medicine Insights. Circulatory, Respiratory and Pulmonary Medicine
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