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Mechanism of airway clearance

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https://www.readbyqxmd.com/read/27870227/aspergillosis-and-the-role-of-mucins-in-cystic-fibrosis
#1
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
#2
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. We recently demonstrated that reduced mucociliary clearance, a characteristic feature of asthma, produces spontaneous type 2 airway inflammation in juvenile Scnn1b-transgenic (Scnn1b-Tg) mice. OBJECTIVE: 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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
https://www.readbyqxmd.com/read/27721661/short-term-pulmonary-rehabilitation-for-a-female-patient-with-chronic-scleroderma-under-a-single-case-research-design
#12
Jirakrit Leelarungrayub, Decha Pinkaew, Khanittha Wonglangka, Wichai Eungpinichpong, Jakkrit Klaphajone
Although previously proposed that chronic scleroderma should be cared for clinically and early rehabilitation should be performed in hospital by a chest physical therapist, little evidence is currently available on its benefits. Therefore, this study demonstrated the benefits of short-term pulmonary rehabilitation during hospitalization in a female patient with chronic scleroderma. The aim of rehabilitation was to improve ventilation and gas exchange by using airway clearance, chest mobilization, and breathing-relearning techniques, including strengthening the respiratory system and the muscles of the limbs by using the BreathMax(®) device and elastic bands...
2016: Clinical Medicine Insights. Circulatory, Respiratory and Pulmonary Medicine
https://www.readbyqxmd.com/read/27698207/high-flow-nasal-cannula-therapy-for-adult-patients
#13
Jian Zhang, Ling Lin, Konghan Pan, Jiancang Zhou, Xiaoyin Huang
High-flow nasal cannula (HFNC) oxygen therapy has several physiological advantages over traditional oxygen therapy devices, including decreased nasopharyngeal resistance, washing out of the nasopharyngeal dead space, generation of positive pressure in the pharynx, increasing alveolar recruitment in the lungs, humidification of the airways, increased fraction of inspired oxygen and improved mucociliary clearance. Recently, the use of HFNC in treating adult critical illness patients has significantly increased, and it is now being used in many patients with a range of different disease conditions...
October 2, 2016: Journal of International Medical Research
https://www.readbyqxmd.com/read/27679445/pulmostent-in-vitro-to-in-vivo-evaluation-of-a-tissue-engineered-endobronchial-stent
#14
Anja Lena Thiebes, Nicola Kelly, Caoimhe A Sweeney, Donnacha J McGrath, Johanna Clauser, Kathrin Kurtenbach, Valentine N Gesche, Weiluan Chen, Robbert Jan Kok, Ulrich Steinseifer, Mark Bruzzi, Barry J O'Brien, Peter E McHugh, Stefan Jockenhoevel, Christian G Cornelissen
Currently, there is no optimal treatment available for end stage tumour patients with airway stenosis. The PulmoStent concept aims on overcoming current hurdles in airway stenting by combining a nitinol stent with a nutrient-permeable membrane, which prevents tumour ingrowth. Respiratory epithelial cells can be seeded onto the cover to restore mucociliary clearance. In this study, a novel hand-braided dog bone stent was developed, covered with a polycarbonate urethane nonwoven and mechanically tested. Design and manufacturing of stent and cover were improved in an iterative process according to predefined requirements for permeability and mechanical properties and finally tested in a proof of concept animal study in sheep for up to 24 weeks...
September 27, 2016: Annals of Biomedical Engineering
https://www.readbyqxmd.com/read/27671059/esculentin-1a-derived-peptides-promote-clearance-of-pseudomonas-aeruginosa-internalized-in-bronchial-cells-of-cystic-fibrosis-patients-and-lung-cell-migration-biochemical-properties-and-a-plausible-mode-of-action
#15
Floriana Cappiello, Antonio Di Grazia, Li-Av Segev-Zarko, Silvia Scali, Loretta Ferrera, Luis Galietta, Alessandro Pini, Yechiel Shai, Y Peter Di, Maria Luisa Mangoni
Pseudomonas aeruginosa is the major microorganism colonizing the respiratory epithelium in cystic fibrosis (CF) sufferers. The widespread use of available antibiotics has drastically reduced their efficacy, and antimicrobial peptides (AMPs) are a promising alternative. Among them, the frog skin-derived AMPs, i.e., Esc(1-21) and its diastereomer, Esc(1-21)-1c, have recently shown potent activity against free-living and sessile forms of P. aeruginosa Importantly, this pathogen also escapes antibiotics treatment by invading airway epithelial cells...
December 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27630174/idiopathic-pulmonary-fibrosis-a-genetic-disease-that-involves-mucociliary-dysfunction-of-the-peripheral-airways
#16
REVIEW
Christopher M Evans, Tasha E Fingerlin, Marvin I Schwarz, David Lynch, Jonathan Kurche, Laura Warg, Ivana V Yang, David A Schwartz
Idiopathic pulmonary fibrosis (IPF) is an incurable complex genetic disorder that is associated with sequence changes in 7 genes (MUC5B, TERT, TERC, RTEL1, PARN, SFTPC, and SFTPA2) and with variants in at least 11 novel loci. We have previously found that 1) a common gain-of-function promoter variant in MUC5B rs35705950 is the strongest risk factor (genetic and otherwise), accounting for 30-35% of the risk of developing IPF, a disease that was previously considered idiopathic; 2) the MUC5B promoter variant can potentially be used to identify individuals with preclinical pulmonary fibrosis and is predictive of radiologic progression of preclinical pulmonary fibrosis; and 3) MUC5B may be involved in the pathogenesis of pulmonary fibrosis with MUC5B message and protein expressed in bronchiolo-alveolar epithelia of IPF and the characteristic IPF honeycomb cysts...
October 2016: Physiological Reviews
https://www.readbyqxmd.com/read/27625638/the-role-of-bacterial-secretion-systems-in-the-virulence-of-gram-negative-airway-pathogens-associated-with-cystic-fibrosis
#17
REVIEW
Sofie Depluverez, Simon Devos, Bart Devreese
Cystic fibrosis (CF) is the most common lethal inherited disorder in Caucasians. It is caused by mutation of the CF transmembrane conductance regulator (CFTR) gene. A defect in the CFTR ion channel causes a dramatic change in the composition of the airway surface fluid, leading to a highly viscous mucus layer. In healthy individuals, the majority of bacteria trapped in the mucus layer are removed and destroyed by mucociliary clearance. However, in the lungs of patients with CF, the mucociliary clearance is impaired due to dehydration of the airway surface fluid...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/27624630/cough-augmentation-techniques-in-the-critically-ill-a-canadian-national-survey
#18
Louise Rose, Neill K Adhikari, Joseph Poon, David Leasa, Douglas A McKim
BACKGROUND: Critically ill mechanically ventilated patients experience impaired airway clearance due to ineffective cough and impaired secretion mobilization. Cough augmentation techniques, including mechanical insufflation-exsufflation (MI-E), manually assisted cough, and lung volume recruitment, improve cough efficiency. Our objective was to describe use, indications, contraindications, interfaces, settings, complications, and barriers to use across Canada. METHODS: An e-mail survey was sent to nominated local survey champions in eligible Canadian units (ICUs, weaning centers, and intermediate care units) with 4 telephone/e-mail reminders...
October 2016: Respiratory Care
https://www.readbyqxmd.com/read/27585394/the-cftr-potentiator-ivacaftor-augments-mucociliary-clearance-abrogating-cftr-inhibition-by-cigarette-smoke
#19
S Vamsee Raju, Vivian Y Lin, Limbo Liu, Carmel M McNicholas, Suman Karki, Peter A Sloane, Liping Tang, Patricia L Jackson, Wei Wang, Landon Wilson, Kevin J Macon, Marina Mazur, John Kappes, Lawrence J DeLucas, Stephen Barnes, Kevin Kirk, Guillermo T Tearney, Steven M Rowe
RATIONALE: Acquired CFTR dysfunction may contribute to COPD pathogenesis and is a potential therapeutic target. OBJECTIVES: To determine the acute effects of cigarette smoke on ion transport and the mucociliary transport apparatus, their mechanistic basis; and whether deleterious effects could be reversed with the CFTR potentiator ivacaftor (VX-770). METHODS: Primary human bronchial epithelial cells (HBE) and human bronchi were exposed to cigarette smoke extract (CSE) and/or ivacaftor...
September 1, 2016: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/27580630/multiciliated-cells-in-animals
#20
REVIEW
Alice Meunier, Juliette Azimzadeh
Many animal cells assemble single cilia involved in motile and/or sensory functions. In contrast, multiciliated cells (MCCs) assemble up to 300 motile cilia that beat in a coordinate fashion to generate a directional fluid flow. In the human airways, the brain, and the oviduct, MCCs allow mucus clearance, cerebrospinal fluid circulation, and egg transportation, respectively. Impairment of MCC function leads to chronic respiratory infections and increased risks of hydrocephalus and female infertility. MCC differentiation during development or repair involves the activation of a regulatory cascade triggered by the inhibition of Notch activity in MCC progenitors...
December 1, 2016: Cold Spring Harbor Perspectives in Biology
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