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Mechanism of airway clearance

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https://www.readbyqxmd.com/read/29453412/pulmonary-antigen-encounter-regulates-the-establishment-of-tissue-resident-cd8-memory-t-cells-in-the-lung-airways-and-parenchyma
#1
Sean R McMaster, Alexander N Wein, Paul R Dunbar, Sarah L Hayward, Emily K Cartwright, Timothy L Denning, Jacob E Kohlmeier
Resident memory CD8 T (T RM ) cells in the lung parenchyma (LP) and airways provide heterologous protection against influenza virus challenge. However, scant knowledge exists regarding factors necessary to establish and maintain lung CD8 T RM . Here we demonstrate that, in contrast to mechanisms described for other tissues, airway, and LP CD8 T RM establishment requires cognate antigen recognition in the lung. Systemic effector CD8 T cells could be transiently pulled into the lung in response to localized inflammation, however these effector cells failed to establish tissue residency unless antigen was present in the pulmonary environment...
February 16, 2018: Mucosal Immunology
https://www.readbyqxmd.com/read/29424930/inhaled-mannitol-for-cystic-fibrosis
#2
REVIEW
Sarah J Nevitt, Judith Thornton, Clare S Murray, Tiffany Dwyer
BACKGROUND: Several agents are used to clear secretions from the airways of people with cystic fibrosis. Mannitol increases mucociliary clearance, but its exact mechanism of action is unknown. The dry powder formulation of mannitol may be more convenient and easier to use compared with established agents which require delivery via a nebuliser. Phase III trials of inhaled dry powder mannitol for the treatment of cystic fibrosis have been completed and it is now available in Australia and some countries in Europe...
February 9, 2018: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/29402960/spatiotemporal-organization-of-cilia-drives-multiscale-mucus-swirls-in-model-human-bronchial-epithelium
#3
Mustapha-Kamel Khelloufi, Etienne Loiseau, Marc Jaeger, Nicolas Molinari, Pascal Chanez, Delphine Gras, Annie Viallat
Mucociliary clearance is a biomechanical mechanism of airway protection. It consists of the active transport along the bronchial tree of the mucus, a fluid propelled by the coordinated beating of a myriad of cilia on the epithelial surface of the respiratory tract. The physics of mucus transport is poorly understood because it involves complex phenomena such as long-range hydrodynamic interactions, active collective ciliary motion, and the complex rheology of mucus. We propose a quantitative physical analysis of the ciliary activity and mucus transport on a large panel of human bronchial cultures from control subjects, patients with asthma and chronic obstructive pulmonary disease obtained from endobronchial biopsies...
February 5, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29391451/atp12a-promotes-mucus-dysfunction-during-type-2-airway-inflammation
#4
Alison T Lennox, Stefanie L Coburn, John A Leech, Elisa M Heidrich, Thomas R Kleyman, Sally E Wenzel, Joseph M Pilewski, Timothy E Corcoran, Mike M Myerburg
Allergic airway disease is known to cause significant morbidity due to impaired mucociliary clearance, however the mechanism that leads to the mucus dysfunction is not entirely understood. Interleukin 13 (IL-13), a key mediator of Type 2 (T2) inflammation, profoundly alters the ion transport properties of airway epithelium. However, these electrophysiological changes cannot explain the thick, tenacious airway mucus that characterizes the clinical phenotype. Here we report that IL-13 dramatically increases the airway surface liquid (ASL) viscosity in cultured primary human bronchial epithelial cells and thereby inhibits mucus clearance...
February 1, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29382534/salvianolic-acid-b-improves-airway-hyperresponsiveness-by-inhibiting-muc5ac-overproduction-associated-with-erk1-2-p38-signaling
#5
Yan Guan, Jian-Ping Zhu, Jian Shen, Yong-Liang Jia, Ya-Chao Jin, Xin-Wei Dong, Qiang-Min Xie
Salvianolic acid B (SalB) is one of the main water-soluble composites from Chinese medicine Dansen (Radix miltiorrhiza). It is used for clinical treatment of various diseases including cardiovascular, lung, Liver, renal and cancers. However, the effects of SalB to allergy induced airway mucin hypersecretion, inflammation and hyperresponsiveness (AHR) remains not clear. Overproduction of airway MUC5AC is a central effector of inflammation that is strongly associated with AHR in asthmatic attack. In this study, we investigated the anti-asthmatic activity and mechanism of SalB in a murine model and human epithelial cells by monitoring changes in mucin expression and secretion, airway inflammation, AHR, and signaling pathways...
January 27, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29373331/the-physiology-of-neonatal-resuscitation
#6
Stuart B Hooper, Marcus J Kitchen, Graeme R Polglase, Charles C Roehr, Arjan B Te Pas
PURPOSE OF REVIEW: As the infant's physiology changes dramatically after birth, modern neonatal resuscitation approaches should detect and be modified in response to these changes. This review describes the changes in respiratory physiology at birth and highlights approaches that can assist these changes. RECENT FINDINGS: To better target assistance given to infants at birth, the changes in lung physiology have been classified into three phases. The first phase involves lung aeration...
January 25, 2018: Current Opinion in Pediatrics
https://www.readbyqxmd.com/read/29367592/persistent-activation-of-interlinked-type-2-airway-epithelial-gene-networks-in-sputum-derived-cells-from-aeroallergen-sensitized-symptomatic-asthmatics
#7
Anya C Jones, Niamh M Troy, Elisha White, Elysia M Hollams, Alexander M Gout, Kak-Ming Ling, Anthony Kicic, Stephen M Stick, Peter D Sly, Patrick G Holt, Graham L Hall, Anthony Bosco
Atopic asthma is a persistent disease characterized by intermittent wheeze and progressive loss of lung function. The disease is thought to be driven primarily by chronic aeroallergen-induced type 2-associated inflammation. However, the vast majority of atopics do not develop asthma despite ongoing aeroallergen exposure, suggesting additional mechanisms operate in conjunction with type 2 immunity to drive asthma pathogenesis. We employed RNA-Seq profiling of sputum-derived cells to identify gene networks operative at baseline in house dust mite-sensitized (HDMS) subjects with/without wheezing history that are characteristic of the ongoing asthmatic state...
January 24, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29321377/development-of-an-airway-mucus-defect-in-the-cystic-fibrosis-rat
#8
Susan E Birket, Joy M Davis, Courtney M Fernandez, Katherine L Tuggle, Ashley M Oden, Kengyeh K Chu, Guillermo J Tearney, Michelle V Fanucchi, Eric J Sorscher, Steven M Rowe
The mechanisms underlying the development and natural progression of the airway mucus defect in cystic fibrosis (CF) remain largely unclear. New animal models of CF, coupled with imaging using micro-optical coherence tomography, can lead to insights regarding these questions. The Cftr-/- (KO) rat allows for longitudinal examination of the development and progression of airway mucus abnormalities. The KO rat exhibits decreased periciliary depth, hyperacidic pH, and increased mucus solid content percentage; however, the transport rates and viscoelastic properties of the mucus are unaffected until the KO rat ages...
January 11, 2018: JCI Insight
https://www.readbyqxmd.com/read/29319936/submucosal-gland-mucus-strand-velocity-is-decreased-in-chronic-rhinosinusitis
#9
Kiranya E Tipirneni, Shaoyan Zhang, Do-Yeon Cho, Jessica Grayson, Daniel F Skinner, Calvin Mackey, Lindsay Moore, Denzel Cole, Catherine G Banks, Bradford A Woodworth
BACKGROUND: Chronic rhinosinusitis (CRS) may be initiated by innately impaired host defense mechanisms that predispose the upper airways to infection. Recent evidence suggests tethering of submucosal gland mucus strands represents an inciting event within cystic fibrosis (CF) airways, occurring prior to onset of chronic infection. Submucosal gland hypertrophy and defective mucociliary clearance (MCC) are present in actively inflamed sinuses, but mucus strand velocity may also be affected as a secondary event, further contributing to chronic disease...
January 10, 2018: International Forum of Allergy & Rhinology
https://www.readbyqxmd.com/read/29311363/il-1-signaling-prevents-alveolar-macrophage-depletion-during-influenza-and-streptococcus-pneumoniae-coinfection
#10
Shruti Bansal, Vijaya Kumar Yajjala, Christopher Bauer, Keer Sun
Influenza and bacterial coinfection is a significant cause of hospitalization and death in humans during influenza epidemics and pandemics. However, the fundamental protective and pathogenic mechanisms involved in this complex virus-host-bacterium interaction remain incompletely understood. In this study, we have developed mild to lethal influenza and Streptococcus pneumoniae coinfection models for comparative analyses of disease pathogenesis. Specifically, wild-type and IL-1R type 1-deficient (Il1r1-/- ) mice were infected with influenza virus and then superchallenged with noninvasive S...
January 8, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29289553/advanced-aging-causes-diaphragm-functional-abnormalities-global-proteome-remodeling-and-loss-of-mitochondrial-cysteine-redox-flexibility-in-mice
#11
Rachel C Kelley, Brian McDonagh, Leonardo F Ferreira
AIM: Inspiratory muscle (diaphragm) function declines with age, contributing to exercise intolerance and impaired airway clearance. Studies of diaphragm dysfunction in rodents have focused on moderate aging (~24months); thus, the impact of advanced age on the diaphragm and potential mechanisms of dysfunction are less clear. Therefore, we aimed to define the effects of advanced age on the mechanics, morphology, and global and redox proteome of the diaphragm. METHODS: We studied diaphragm from young (6months) and very old male mice (30months)...
December 28, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/29281691/impaired-pge2-stimulated-cl-and-hco3-secretion-contributes-to-cystic-fibrosis-airway-disease
#12
Zachary M Sellers, Beate Illek, Miriam Frankenthal Figueira, Gopika Hari, Nam Soo Joo, Eric Sibley, Jackson Souza-Menezes, Marcelo M Morales, Horst Fischer, Jeffrey J Wine
BACKGROUND: Airway mucociliary clearance (MCC) is an important defense mechanism against pulmonary infections and is compromised in cystic fibrosis (CF). Cl- and HCO3- epithelial transport are integral to MCC. During pulmonary infections prostaglandin E2 (PGE2) production is abundant. AIM: To determine the effect of PGE2 on airway Cl- and HCO3- secretion and MCC in normal and CF airways. METHODS: We examined PGE2 stimulated MCC, Cl- and HCO3- secretion using ferret trachea, human bronchial epithelial cell cultures (CFBE41o- with wildtype CFTR (CFBE41 WT) or homozygous F508del CFTR (CFBE41 CF) and human normal bronchial submucosal gland cell line (Calu-3) in Ussing chambers with or without pH-stat...
2017: PloS One
https://www.readbyqxmd.com/read/29244804/conditional-knockout-mice-for-the-distal-appendage-protein-cep164-reveal-its-essential-roles-in-airway-multiciliated-cell-differentiation
#13
Saul S Siller, Himanshu Sharma, Shuai Li, June Yang, Yong Zhang, Michael J Holtzman, Wipawee Winuthayanon, Holly Colognato, Bernadette C Holdener, Feng-Qian Li, Ken-Ichi Takemaru
Multiciliated cells of the airways, brain ventricles, and female reproductive tract provide the motive force for mucociliary clearance, cerebrospinal fluid circulation, and ovum transport. Despite their clear importance to human biology and health, the molecular mechanisms underlying multiciliated cell differentiation are poorly understood. Prior studies implicate the distal appendage/transition fiber protein CEP164 as a central regulator of primary ciliogenesis; however, its role in multiciliogenesis remains unknown...
December 15, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29187536/inflammasome-antagonism-by-human-parainfluenza-virus-type-3-c-protein
#14
Niraj K Shil, Swechha M Pokharel, Amiya K Banerjee, Michael Hoffman, Santanu Bose
Human parainfluenza virus type 3 (HPIV3) is a negative-sense single-stranded RNA virus belonging to the paramyxoviridae family. HPIV3 is a lung tropic virus causing airway diseases including pneumonia, croup, and bronchiolitis during infancy and childhood. Activation of inflammasome by pathogens results in production of pro-inflammatory cytokines like IL-1β during infection. Thus, inflammasome mediated pro-inflammatory response plays a critical role in regulating immune response and virus clearance. Inflammasome is a multimeric protein complex triggering caspase-1 activation...
November 29, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29184554/il-17-and-tnf-%C3%AE-are-key-mediators-of-moraxella-catarrhalis-triggered-exacerbation-of-allergic-airway-inflammation
#15
Safa Alnahas, Stefanie Hagner, Hartmann Raifer, Ayse Kilic, Georg Gasteiger, Reinier Mutters, Anne Hellhund, Immo Prinz, Olaf Pinkenburg, Alexander Visekruna, Holger Garn, Ulrich Steinhoff
Alterations of the airway microbiome are often associated with pulmonary diseases. For example, detection of the bacterial pathogen Moraxella catarrhalis in the upper airways is linked with an increased risk to develop or exacerbate asthma. However, the mechanisms by which M. catarrhalis augments allergic airway inflammation (AAI) remain unclear. We here characterized the cellular and soluble mediators of M. catarrhalis triggered excacerbation of AAI in wt and IL-17 deficient as well as in animals treated with TNF-α and IL-6 neutralizing antibodies...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29174453/correlation-of-high-flow-nasal-cannula-outlet-area-with-gas-clearance-and-pressure-in-adult-upper-airway-replicas
#16
REVIEW
Charles P Moore, Ira M Katz, Georges Caillibotte, Warren H Finlay, Andrew R Martin
BACKGROUND: Primary benefits of high flow nasal cannula therapy include washout of carbon dioxide rich exhaled gas and increased airway pressures during tidal breathing. This work reports on the influence of high flow nasal cannula outlet area on upper airways gas clearance and tracheal pressures using measurements in five realistic adult nose-throat airway replicas. METHODS: Two commercial high flow nasal cannulas and one generic nasal cannula of varying size were compared...
November 11, 2017: Clinical Biomechanics
https://www.readbyqxmd.com/read/29163395/role-of-soluble-innate-effector-molecules-in-pulmonary-defense-against-fungal-pathogens
#17
REVIEW
Soledad R Ordonez, Edwin J A Veldhuizen, Martin van Eijk, Henk P Haagsman
Fungal infections of the lung are life-threatening but rarely occur in healthy, immunocompetent individuals, indicating efficient clearance by pulmonary defense mechanisms. Upon inhalation, fungi will first encounter the airway surface liquid which contains several soluble effector molecules that form the first barrier of defense against fungal infections. These include host defense peptides, like LL-37 and defensins that can neutralize fungi by direct killing of the pathogen, and collectins, such as surfactant protein A and D, that can aggregate fungi and stimulate phagocytosis...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29156907/the-palliative-care-needs-for-those-advanced-neurology-patients-on-mechanical-ventilator-support
#18
Tsz Kin Kwok
There are mainly two types of needs for the ventilator users with severe neurological diseases: respiratory related needs include mode of ventilation selection, mode of ventilator prescription, maintaining lung recruitment and good airway clearance; non-respiratory related needs include substantial nursing care, adequate nutrition, accessible communication and psychological support. All these are important to maintain the quality of life of these patients.
September 13, 2017: Annals of Palliative Medicine
https://www.readbyqxmd.com/read/29114887/cough-strength-and-expiratory-force-in-aspirating-and-nonaspirating-postradiation-head-and-neck-cancer-survivors
#19
Katherine A Hutcheson, Martha P Barrow, Carla L Warneke, Yiqun Wang, George Eapen, Stephen Y Lai, Denise A Barringer, Emily K Plowman, Jan S Lewin
OBJECTIVE: Expiratory functions that clear aspiration from the airway are compromised in patients with neurogenic dysphagia for whom cough and expiratory force may be impaired by the primary disease process. The relationship between expiratory function, cough, and aspiration is less clear in head and neck cancer (HNC) survivors for whom the disease process does not directly impact the lower respiratory system. Our objective was to compare mechanisms of airway clearance (expiratory force and cough) with aspiration status in postradiated HNC survivors...
November 8, 2017: Laryngoscope
https://www.readbyqxmd.com/read/29109332/hydrogen-enriched-water-eliminates-fine-particles-from-the-lungs-and-blood-by-enhancing-phagocytic-activity
#20
Jieun Choi, Eun Suk An, Young-Hwan Ban, Da Woom Seo, Tae-Su Kim, Sung-Pyo Lee, You Lin, Ehn-Kyoung Choi, Yun-Bae Kim
Particulate matters (PM) are one of the major body burdens leading to diseases. We investigated the capacities of a hydrogen-enriched water (HW) eliminating carbon nanoparticles (CNP) and carbon microparticles (CMP) from the lungs and blood, respectively. In CNP-elimination test, rats were orally administered with purified water (PW) or HW (10 or 30 mL/kg/day) for 10 weeks. At the time point of 4 weeks, the rats were challenged with intratracheal instillation of CNP (4 mg). CNP accumulated in the airways and alveoli, and induced inflammatory lesions...
November 1, 2017: Journal of Biomedical Research
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