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Full-Text Articles in Respiratory System

Hypersensitivity Of Vagal Pulmonary Afferents Induced By Tumor Necrosis Factor Alpha In Mice, Ruei-Lung Lin, Qihai Gu, Lu-Yuan Lee Jun 2017

Hypersensitivity Of Vagal Pulmonary Afferents Induced By Tumor Necrosis Factor Alpha In Mice, Ruei-Lung Lin, Qihai Gu, Lu-Yuan Lee

Physiology Faculty Publications

Tumor necrosis factor alpha (TNFα), a pro-inflammatory cytokine, plays a significant role in the pathogenesis of allergic asthma. Inhalation of TNFα also induces airway hyperresponsiveness in healthy human subjects, and the underlying mechanism is not fully understood. A recent study reported that TNFα caused airway inflammation and a sustained elevation of pulmonary chemoreflex responses in mice, suggesting a possible involvement of heightened sensitivity of vagal pulmonary C-fibers. To investigate this possibility, the present study aimed to investigate the effect of a pretreatment with TNFα on the sensitivity of vagal pulmonary afferents in anesthetized mice. After TNFα (10 μg/ml, 0.03 ml) …


Cigarette Smoke Impairs A2a Adenosine Receptor Mediated Wound Repair Through Up-Regulation Of Duox-1 Expression., Zhi Tian, Hui Zhang, Jendayi Dixon, Nicole Traphagen, Todd A. Wyatt, Kusum K. Kharbanda, Samantha Simet, Narasaiah Kolliputi, Diane S Allen-Gipson Mar 2017

Cigarette Smoke Impairs A2a Adenosine Receptor Mediated Wound Repair Through Up-Regulation Of Duox-1 Expression., Zhi Tian, Hui Zhang, Jendayi Dixon, Nicole Traphagen, Todd A. Wyatt, Kusum K. Kharbanda, Samantha Simet, Narasaiah Kolliputi, Diane S Allen-Gipson

Journal Articles: Pulmonary & Critical Care Med

Cigarette smoke (CS) exposure and intrinsic factors such as the NADPH oxidases produce high levels of reactive oxygen species (ROS), ensuing inflammatory tissue injury. We previously demonstrated that CS-generated ROS, particularly hydrogen peroxide (H2O2), impaired adenosine stimulated wound repair. We hypothesized that CS exposure modulates expression of Dual oxidase 1 (Duox-1), a NADPH oxidases known to generate H2O2. To test this hypothesis, we used human bronchial epithelial cell line Nuli-1 and C57BL/6 mice. Cells were treated with 5% CS extract (CSE) for various periods of time, and mice were exposed to whole body CS for six weeks. Both CSE and …


Effect Of Low-Level Co2 On Innate Inflammatory Protein Response To Organic Dust From Swine Confinement Barns., David Schneberger, Jane M. Devasure, Kristina L. Bailey, Debra J. Romberger, Todd A. Wyatt Mar 2017

Effect Of Low-Level Co2 On Innate Inflammatory Protein Response To Organic Dust From Swine Confinement Barns., David Schneberger, Jane M. Devasure, Kristina L. Bailey, Debra J. Romberger, Todd A. Wyatt

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Organic hog barn dust (HDE) exposure induces lung inflammation and long-term decreases in lung function in agricultural workers. While concentrations of common gasses in confined animal facilities are well characterized, few studies have been done addressing if exposure to elevated barn gasses impacts the lung immune response to organic dusts. Given the well documented effects of hypercapnia at much higher levels we hypothesized that CO2 at 8 h exposure limit levels (5000 ppm) could alter innate immune responses to HDE.

METHODS: Using a mouse model, C57BL/6 mice were nasally instilled with defined barn dust extracts and then housed in …


Effect Of Low-Level Co2 On Innate Inflammatory Protein Response To Organic Dust From Swine Confinement Barns., David Schneberger, Jane M. Devasure, Kristina L. Bailey, Debra J. Romberger, Todd A. Wyatt Mar 2017

Effect Of Low-Level Co2 On Innate Inflammatory Protein Response To Organic Dust From Swine Confinement Barns., David Schneberger, Jane M. Devasure, Kristina L. Bailey, Debra J. Romberger, Todd A. Wyatt

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Organic hog barn dust (HDE) exposure induces lung inflammation and long-term decreases in lung function in agricultural workers. While concentrations of common gasses in confined animal facilities are well characterized, few studies have been done addressing if exposure to elevated barn gasses impacts the lung immune response to organic dusts. Given the well documented effects of hypercapnia at much higher levels we hypothesized that CO2 at 8 h exposure limit levels (5000 ppm) could alter innate immune responses to HDE.

METHODS: Using a mouse model, C57BL/6 mice were nasally instilled with defined barn dust extracts and then housed in …


Longitudinal Cardiovascular Outcomes Of Sleep Disordered Breathing In Children: A Meta-Analysis And Systematic Review., Zarmina Ehsan, Stacey L. Ishman, Thomas R. Kimball, Nanhua Zhang, Yuanshu Zou, Raouf S. Amin Mar 2017

Longitudinal Cardiovascular Outcomes Of Sleep Disordered Breathing In Children: A Meta-Analysis And Systematic Review., Zarmina Ehsan, Stacey L. Ishman, Thomas R. Kimball, Nanhua Zhang, Yuanshu Zou, Raouf S. Amin

Manuscripts, Articles, Book Chapters and Other Papers

Objectives: The presence of sleep disordered breathing (SDB) is known to impact long-term cardiovascular morbidity in adults; however, the long-term effects in children are poorly understood. We aimed to systematically review and synthesize studies published to date on the long-term effects of SDB in children.

Study Design: Meta-analysis and systematic review using PubMed, CINAHL, Embase, and Scopus (all indexed years).

Methods: We searched for English-language articles containing original human data from prospective studies, with ≥7 participants, in children ≤18 years of age. Data regarding study design, demographics, clinical characteristics, outcomes, level of evidence, and risk of bias were obtained. Articles …


Nicotinamide Adenine Dinucleotide Phosphate Oxidase 2 Regulates Lps-Induced Inflammation And Alveolar Remodeling In The Developing Lung., Heather Menden, Sheng Xia, Sherry M. Mabry, Angels Navarro, Michael F. Nyp, Venkatesh Sampath Dec 2016

Nicotinamide Adenine Dinucleotide Phosphate Oxidase 2 Regulates Lps-Induced Inflammation And Alveolar Remodeling In The Developing Lung., Heather Menden, Sheng Xia, Sherry M. Mabry, Angels Navarro, Michael F. Nyp, Venkatesh Sampath

Manuscripts, Articles, Book Chapters and Other Papers

In premature infants, sepsis is associated with alveolar simplification manifesting as bronchopulmonary dysplasia. The redox-dependent mechanisms underlying sepsis-induced inflammation and alveolar remodeling in the immature lung remain unclear. We developed a neonatal mouse model of sepsis-induced lung injury to investigate whether nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) regulates Toll-like receptor (TLR)-mediated inflammation and alveolar remodeling. Six-day-old NOX2


Early Cumulative Supplemental Oxygen Predicts Bronchopulmonary Dysplasia In High Risk Extremely Low Gestational Age Newborns., Katherine C. Wai, Michael A. Kohn, Roberta A. Ballard, William E. Truog, Dennis M. Black, Jeanette M. Asselin, Philip L. Ballard, Elizabeth E. Rogers, Roberta L. Keller, Trial Of Late Surfactant (Tolsurf) Study Group Oct 2016

Early Cumulative Supplemental Oxygen Predicts Bronchopulmonary Dysplasia In High Risk Extremely Low Gestational Age Newborns., Katherine C. Wai, Michael A. Kohn, Roberta A. Ballard, William E. Truog, Dennis M. Black, Jeanette M. Asselin, Philip L. Ballard, Elizabeth E. Rogers, Roberta L. Keller, Trial Of Late Surfactant (Tolsurf) Study Group

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: To assess the prognostic accuracy of early cumulative supplemental oxygen (CSO) exposure for prediction of bronchopulmonary dysplasia (BPD) or death, and to evaluate the independent association of CSO with BPD or death.

STUDY DESIGN: We performed a secondary analysis of the Trial of Late Surfactant, which enrolled 511 infants born at ≤28 weeks gestational age who were mechanically ventilated at 7-14 days of life. Our primary outcome was BPD or death at 36 weeks postmenstrual age, as determined by a physiological oxygen/flow challenge. Average daily supplemental oxygen (fraction of inspired oxygen - 0.21) was calculated. CSO was calculated as …


Human Metapneumovirus Induces Reorganization Of The Actin Cytoskeleton For Direct Cell-To-Cell Spread, Farah El Najjar, Nicolás Cifuentes-Muñoz, Jing Chen, Haining Zhu, Ursula J. Buchholz, Carole L. Moncman, Rebecca Ellis Dutch Sep 2016

Human Metapneumovirus Induces Reorganization Of The Actin Cytoskeleton For Direct Cell-To-Cell Spread, Farah El Najjar, Nicolás Cifuentes-Muñoz, Jing Chen, Haining Zhu, Ursula J. Buchholz, Carole L. Moncman, Rebecca Ellis Dutch

Molecular and Cellular Biochemistry Faculty Publications

Paramyxovirus spread generally involves assembly of individual viral particles which then infect target cells. We show that infection of human bronchial airway cells with human metapneumovirus (HMPV), a recently identified paramyxovirus which causes significant respiratory disease, results in formation of intercellular extensions and extensive networks of branched cell-associated filaments. Formation of these structures is dependent on actin, but not microtubule, polymerization. Interestingly, using a co-culture assay we show that conditions which block regular infection by HMPV particles, including addition of neutralizing antibodies or removal of cell surface heparan sulfate, did not prevent viral spread from infected to new target cells. …


Hdac6 Inhibition Prevents Tnf-Α-Induced Caspase 3 Activation In Lung Endothelial Cell And Maintains Cell-Cell Junctions, Jinyan Yu, Mengshi Ma, Zhongsen Ma, Jian Fu Jul 2016

Hdac6 Inhibition Prevents Tnf-Α-Induced Caspase 3 Activation In Lung Endothelial Cell And Maintains Cell-Cell Junctions, Jinyan Yu, Mengshi Ma, Zhongsen Ma, Jian Fu

Center for Research on Environmental Disease Faculty Publications

Pro-inflammatory mediators such as TNF-α induce caspase activation in endothelial cells, which leads to degradation of cellular proteins, induction of apoptotic signaling, and endothelial cell dysfunction. New therapeutic agents that can inhibit caspase activation may provide protection against inflammatory injury to endothelial cells. In the present study, we examined the effects of selective histone deacetylase 6 (HDAC6) inhibition on TNF-α induced caspase 3 activation and cell-cell junction dysfunction in lung endothelial cells. We also assessed the protective effects of HDAC6 inhibition against lung inflammatory injury in a mouse model of endotoxemia. We demonstrated that selective HDAC6 inhibition or knockdown of …


The Utilization Of Exogenous Surfactant In The Neonate, Katherine Thorkildsen Apr 2016

The Utilization Of Exogenous Surfactant In The Neonate, Katherine Thorkildsen

Senior Honors Theses

Respiratory distress syndrome (RDS) is a common consequence of pulmonary immaturity in the lungs of neonates. RDS is the result of the deficient secretion of endogenous surfactant, causing increased surface tension in the alveolar sacs leading to respiratory compromise. RDS is more common in the preterm neonate but can be experienced by neonates at any gestational age. Treatment for RDS formerly consisted of mechanical ventilation and oxygen therapy to treat and relieve symptoms but not the cause. A new treatment method, developed largely in the 1980s and 90s is the use of exogenous surfactant to treat the deficiency exhibited in …


Correlation Of Maximal Inspiratory Pressure To Transdiaphragmatic Twitch Pressure In Intensive Care Unit Patients, Gerald S. Supinski, Philip M. Westgate, Leigh Ann Callahan Mar 2016

Correlation Of Maximal Inspiratory Pressure To Transdiaphragmatic Twitch Pressure In Intensive Care Unit Patients, Gerald S. Supinski, Philip M. Westgate, Leigh Ann Callahan

Internal Medicine Faculty Publications

Background: Respiratory muscle weakness contributes to respiratory failure in ICU patients. Unfortunately, assessment of weakness is difficult since the most objective test, transdiaphragmatic pressure in response to phrenic nerve stimulation (PdiTw), is difficult to perform. While most clinicians utilize maximum inspiratory pressure (Pimax) to assess strength, the relationship of this index to PdiTw has not been evaluated in a large ICU population. The purpose of the present study was to assess both PdiTw and Pimax in ICU patients to determine how these indices correlate with each other, what factors influence these indices, and how well these indices predict outcomes.

Methods: …


Secondhand Aerosol Exposure During Mechanical Ventilation With And Without Expiratory Filters: An In-Vitro Study, Arzu Ari, James B. Fink, Susan P. Pilbeam Jan 2016

Secondhand Aerosol Exposure During Mechanical Ventilation With And Without Expiratory Filters: An In-Vitro Study, Arzu Ari, James B. Fink, Susan P. Pilbeam

Respiratory Therapy Faculty Publications

Background: Concerns have been expressed about risk of exposure to exhaled aerosols to ICU personnel.

AIM: To quantify amount of aerosol collected at the exhaust outlet of mechanical ventilators operated with and without filters in the expiratory limb.

Methods: Two categories of ventilators were tested: (1) Ventilators without Proprietary Filters: Servo-i (Maquet) and Galileo (Hamilton) and (2) Ventilator with proprietary filters: PB 840 (Covidien). Each ventilator was attached to a simple test lung and operated with VT 500 ml, RR 20 bpm, PIF 50 L/min, PEEP 5 cmH2O. Four separate doses of albuterol (2.5 mg/3mL) were administered via jet nebuliser …


Drug Delivery Interfaces: A Way To Optimize Inhalation Therapy In Spontaneously Breathing Children, Arzu Ari Jan 2016

Drug Delivery Interfaces: A Way To Optimize Inhalation Therapy In Spontaneously Breathing Children, Arzu Ari

Respiratory Therapy Faculty Publications

There are several different types of drug delivery interfaces available on the market. Using the right interface for aerosol drug delivery to children is essential for effective inhalation therapy. However, clinicians usually focus on selecting the right drug-device combination and often overlook the importance of interface selection that lead to suboptimal drug delivery and therapeutic response in neonates and pediatrics. Therefore, it is necessary to critically assess each interface and understand its advantage and disadvantages in aerosol drug delivery to this patient population. The purpose of this paper is to provide a critical assessment of drug delivery interfaces used for …


Complications Of Prone Positioning During Extracorporeal Membrane Oxygenation For Respiratory Failure: A Systematic Review, Rachel Culbreth, Lynda T. Goodfellow Jan 2016

Complications Of Prone Positioning During Extracorporeal Membrane Oxygenation For Respiratory Failure: A Systematic Review, Rachel Culbreth, Lynda T. Goodfellow

Respiratory Therapy Faculty Publications

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is often used in patients with severe respiratory failure to improve oxygenation and survival. ECMO gives the lungs an opportunity to rest and recover. The addition of prone positioning therapy used concurrently with ECMO can further aid in optimizing alveolar recruitment and reducing ventilator-induced lung injury, ultimately resulting in fewer ICU admission days and improved overall survival. The objective of this review is to perform a systematic analysis of the complications reported with prone positioning and ECMO in the adult population and to briefly report on the patient outcomes in the studies. METHODS: PubMed, MEDLINE, …


Atrial Thrombus In A Premature Newborn Following Cardio-Pulmonary Resuscitation, Syed Rehan Ali, Shakeel Ahmed, Nadeem Aslam, Heeramani Lohana Jan 2016

Atrial Thrombus In A Premature Newborn Following Cardio-Pulmonary Resuscitation, Syed Rehan Ali, Shakeel Ahmed, Nadeem Aslam, Heeramani Lohana

Department of Paediatrics and Child Health

Critically ill newborns, whether term or preterm, are at great risk for developing symptomatic thromboembolic disease. Comorbidities like inflammation, DIC, fluctuations in cardiac output, congenital heart disease, as well as central venous or arterial catheters, are the predisposing risk factors. Clinically symptomatic or asymptomatic cases are usually picked up by echocardiography, usually done for other indications. Management usually comprises of observation, heparin therapy, thrombo-embolectomy, and catheter directed revascularization. We present a case of premature neonate who developed thrombus at inter-atrial septum as a possible consequence of cardiopulmonary resuscitation, detected by echocardiography. Conversely, there is always a possibility of paradoxical emboli …


Evolution Of An Interprofessional Patient Skills Course With The Incorporation Of Simulation Scenarios, Lutana Haan, Rosemary Macy, Leslie E. Kendrick Jan 2016

Evolution Of An Interprofessional Patient Skills Course With The Incorporation Of Simulation Scenarios, Lutana Haan, Rosemary Macy, Leslie E. Kendrick

Respiratory Therapy Faculty Publications and Presentations

A university level interprofessional patient care skills course including Nursing, Radiologic Sciences, and Respiratory Care students has evolved over 20 years. The course includes a lecture and laboratory portion with specific content and skills focused on principles common to the three disciplines. Students are placed in interprofessional groups during lab to practice and learn together including a simulation scenario on each week’s content. This educational strategy has enhanced the students’ teamwork and communication skills and prepared them to apply these skills to clinical practice. Further research is needed to look at IPE undergraduate healthcare course outcomes related to teamwork.


Hsp90 Inhibition Suppresses Nf-Κb Transcriptional Activation Via Sirt-2 In Human Lung Microvascular Endothelial Cells, Gagan S. Thangjam, Charalampos Birmpas, Nektarios Barabutis, Betsy W. Gregory, Mary Ann Clemens, Joseph R. Newton, David Fulton, John D. Catravas Jan 2016

Hsp90 Inhibition Suppresses Nf-Κb Transcriptional Activation Via Sirt-2 In Human Lung Microvascular Endothelial Cells, Gagan S. Thangjam, Charalampos Birmpas, Nektarios Barabutis, Betsy W. Gregory, Mary Ann Clemens, Joseph R. Newton, David Fulton, John D. Catravas

Bioelectrics Publications

The ability of anti-heat shock protein 90 (Hsp90) drugs to attenuate NF-κB-mediated transcription is the major basis for their anti-inflammatory properties. While the molecular mechanisms underlying this effect are not clear, they appear to be distinct in human endothelial cells. We now show for the first time that type 2 sirtuin (Sirt-2) histone deacetylase binds human NF-κB target gene promoter and prevents the recruitment of NF-κB proteins and subsequent assembly of RNA polymerase II complex in human lung microvascular endothelial cells. Hsp90 inhibitors stabilize the Sirt-2/promoter interaction and impose a “transcriptional block,” which is reversed by either inhibition or downregulation …


Right-Sided Congenital Diaphragmatic Hernia And Myelomeningocele: A Rare Association, Syed Rehan Ali, Shakeel Ahmed Jan 2016

Right-Sided Congenital Diaphragmatic Hernia And Myelomeningocele: A Rare Association, Syed Rehan Ali, Shakeel Ahmed

Department of Paediatrics and Child Health

Congenital diaphragmatic hernia (CDH) is a rare birth defect with a prevalence of < 0.5 per 1,000 live births. Majority of these defects are left-sided as most studies suggest that frequency of right-sided CDH was 10% of the total. The association of CDH with myelomeningocele (MMC) is extremely rare; as in Sweed's study of 116 consecutive cases of CDH, the incidence of associated MMC with CDH was stated as 4.3%. There has been one previous case report of leftsided CDH, MMC and hydrocephalus prenatally diagnosed; but to the best of authors' knowledge, this is the first reported case of the above constellation with a right-sided CDH diagnosed prenatally.


Myd88 In Lung Resident Cells Governs Airway Inflammatory And Pulmonary Function Responses To Organic Dust Treatment., Jill A. Poole, Todd A. Wyatt, Debra J. Romberger, Elizabeth Staab, Samantha Simet, Stephen J. Reynolds, Joseph H. Sisson, Tammy Kielian Sep 2015

Myd88 In Lung Resident Cells Governs Airway Inflammatory And Pulmonary Function Responses To Organic Dust Treatment., Jill A. Poole, Todd A. Wyatt, Debra J. Romberger, Elizabeth Staab, Samantha Simet, Stephen J. Reynolds, Joseph H. Sisson, Tammy Kielian

Journal Articles: Pulmonary & Critical Care Med

Inhalation of organic dusts within agriculture environments contributes to the development and/or severity of airway diseases, including asthma and chronic bronchitis. MyD88 KO (knockout) mice are nearly completely protected against the inflammatory and bronchoconstriction effects induced by acute organic dust extract (ODE) treatments. However, the contribution of MyD88 in lung epithelial cell responses remains unclear. In the present study, we first addressed whether ODE-induced changes in epithelial cell responses were MyD88-dependent by quantitating ciliary beat frequency and cell migration following wounding by electric cell-substrate impedance sensing. We demonstrate that the normative ciliary beat slowing response to ODE is delayed in …


Cfap54 Is Required For Proper Ciliary Motility And Assembly Of The Central Pair Apparatus In Mice., Casey W. Mckenzie, Branch Craige, Tiffany V. Kroeger, Rozzy Finn, Todd A. Wyatt, Joseph H. Sisson, Jacqueline A. Pavlik, University Of Massachusetts Medical School, Gregory M. Hendricks, George B. Witman, Lance Lee Sep 2015

Cfap54 Is Required For Proper Ciliary Motility And Assembly Of The Central Pair Apparatus In Mice., Casey W. Mckenzie, Branch Craige, Tiffany V. Kroeger, Rozzy Finn, Todd A. Wyatt, Joseph H. Sisson, Jacqueline A. Pavlik, University Of Massachusetts Medical School, Gregory M. Hendricks, George B. Witman, Lance Lee

Journal Articles: Pulmonary & Critical Care Med

Motile cilia and flagella play critical roles in fluid clearance and cell motility, and dysfunction commonly results in the pediatric syndrome primary ciliary dyskinesia (PCD). CFAP221, also known as PCDP1, is required for ciliary and flagellar function in mice and Chlamydomonas reinhardtii, where it localizes to the C1d projection of the central microtubule apparatus and functions in a complex that regulates flagellar motility in a calcium-dependent manner. We demonstrate that the genes encoding the mouse homologues of the other C. reinhardtii C1d complex members are primarily expressed in motile ciliated tissues, suggesting a conserved function in mammalian motile cilia. The …


Exercise Improves Host Response To Influenza Viral Infection In Obese And Non-Obese Mice Through Different Mechanisms., Kristi J. Warren, Molly M. Olson, Nicholas J. Thompson, Mackenzie L. Cahill, Todd A. Wyatt, Kyoungjin J. Yoon, Christina M. Loiacono, Marian L. Kohut Jun 2015

Exercise Improves Host Response To Influenza Viral Infection In Obese And Non-Obese Mice Through Different Mechanisms., Kristi J. Warren, Molly M. Olson, Nicholas J. Thompson, Mackenzie L. Cahill, Todd A. Wyatt, Kyoungjin J. Yoon, Christina M. Loiacono, Marian L. Kohut

Journal Articles: Pulmonary & Critical Care Med

Obesity has been associated with greater severity of influenza virus infection and impaired host defense. Exercise may confer health benefits even when weight loss is not achieved, but it has not been determined if regular exercise improves immune defense against influenza A virus (IAV) in the obese condition. In this study, diet-induced obese mice and lean control mice exercised for eight weeks followed by influenza viral infection. Exercise reduced disease severity in both obese and non-obese mice, but the mechanisms differed. Exercise reversed the obesity-associated delay in bronchoalveolar-lavage (BAL) cell infiltration, restored BAL cytokine and chemokine production, and increased ciliary …


Coculture Of Staphylococcus Aureus With Pseudomonas Aeruginosa Drives S. Aureus Towards Fermentative Metabolism And Reduced Viability In A Cystic Fibrosis Model, Laura M. Filkins, Jyoti A. Graber, Daniel G. Olson, Emily L. Dolben, Lee Lynd, Sabin Bhuju, George A. O'Toole Apr 2015

Coculture Of Staphylococcus Aureus With Pseudomonas Aeruginosa Drives S. Aureus Towards Fermentative Metabolism And Reduced Viability In A Cystic Fibrosis Model, Laura M. Filkins, Jyoti A. Graber, Daniel G. Olson, Emily L. Dolben, Lee Lynd, Sabin Bhuju, George A. O'Toole

Dartmouth Scholarship

The airways of patients with cystic fibrosis are colonized with diverse bacterial communities that change dynamically during pediatric years and early adulthood. Staphylococcus aureus is the most prevalent pathogen during early childhood, but during late teens and early adulthood, a shift in microbial composition occurs leading to Pseudomonas aeruginosa community predominance in ∼50% of adults. We developed a robust dual-bacterial in vitro coculture system of P. aeruginosa and S. aureus on monolayers of human bronchial epithelial cells homozygous for the ΔF508 cystic fibrosis transmembrane conductance regulator (CFTR) mutation to better model the mechanisms of this interaction. We show that P. …


Gait Mechanics In Patients With Chronic Obstructive Pulmonary Disease., Jennifer M. Yentes, Kendra Schmid, Daniel Blanke, Debra J. Romberger, Stephen I. Rennard, Nicholas Stergiou Feb 2015

Gait Mechanics In Patients With Chronic Obstructive Pulmonary Disease., Jennifer M. Yentes, Kendra Schmid, Daniel Blanke, Debra J. Romberger, Stephen I. Rennard, Nicholas Stergiou

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by the frequent association of disease outside the lung. The objective of this study was to determine the presence of biomechanical gait abnormalities in COPD patients compared to healthy controls while well rested and without rest.

METHODS: Patients with COPD (N = 17) and aged-matched, healthy controls (N = 21) walked at their self-selected pace down a 10-meter walkway while biomechanical gait variables were collected. A one-minute rest was given between each of the five collected trials to prevent tiredness (REST condition). Patients with COPD then walked at a self-selected pace on …


The Role Of Il-27 In Susceptibility To Post-Influenza Staphylococcus Aureus Pneumonia, Keven M. Robinson, Benjamin Lee, Erich V Scheller, Sivanarayana Mandalapu, Richard I. Enelow Feb 2015

The Role Of Il-27 In Susceptibility To Post-Influenza Staphylococcus Aureus Pneumonia, Keven M. Robinson, Benjamin Lee, Erich V Scheller, Sivanarayana Mandalapu, Richard I. Enelow

Dartmouth Scholarship

Influenza is a common respiratory virus and Staphylococcus aureus frequently causes secondary pneumonia during influenza infection, leading to increased morbidity and mortality. Influenza has been found to attenuate subsequent Type 17 immunity, enhancing susceptibility to secondary bacterial infections. IL-27 is known to inhibit Type 17 immunity, suggesting a potential critical role for IL-27 in viral and bacterial co-infection.


Use Of Aerosol Drug Therapy In Pulmonary Rehabilitation, Arzu Ari Jan 2015

Use Of Aerosol Drug Therapy In Pulmonary Rehabilitation, Arzu Ari

Respiratory Therapy Faculty Publications

Clinical applications of pulmonary rehabilitation are patientfocused and consist of individualized therapies such as aerosol drug therapy, airway clearance, chest physical therapy, exercise, and patient education. Devices that are used in aerosol drug delivery are divided into the following 3 categories: (1) small volume nebulizers, (2) metered-dose inhalers, and (3) dry powder inhalers. Although these devices are commonly used for the treatment of patients with pulmonary diseases, there are a limited number of objective studies on the physiologic and clinical effects of aerosol drug therapy on pulmonary rehabilitation. The purpose of this review paper is to explain all the devices …


Performance Comparisons Of Jet And Mesh Nebulizers Using Different Interfaces In Simulated Spontaneously Breathing Adults And Children, Arzu Ari, Armèle Dornelas De Andrade, Meryl M. Sheard, Bshayer R. Alhamad, James B. Fink Jan 2015

Performance Comparisons Of Jet And Mesh Nebulizers Using Different Interfaces In Simulated Spontaneously Breathing Adults And Children, Arzu Ari, Armèle Dornelas De Andrade, Meryl M. Sheard, Bshayer R. Alhamad, James B. Fink

Respiratory Therapy Faculty Publications

Background: Different types of nebulizers and interfaces are used for the treatment of adults and children with pulmonary diseases. The purpose of this study was to determine the efficiency of a mesh nebulizer (MN) with a proprietary adapter and a jet nebulizer (JN) under different configurations in adult and pediatric models of spontaneous breathing. We hypothesize that delivery efficiency of JN and MN will differ depending on the interface used during aerosol therapy in simulated spontaneously breathing adult and pediatric models. While we expect that aerosol delivery with JN will be less efficient than MN, we also hypothesize that lung …


Histone Deacetylase Inhibitors Prevent Pulmonary Endothelial Hyperpermeability And Acute Lung Injury By Regulating Heat Shock Protein 90 Function, Atul D. Joshi, Nektarios Barabutis, Charalampos Birmpas, Christiana Dimitropoulou, Gagan Thangjam, Mary Cherian-Shaw, John Dennison, John D. Catravas Jan 2015

Histone Deacetylase Inhibitors Prevent Pulmonary Endothelial Hyperpermeability And Acute Lung Injury By Regulating Heat Shock Protein 90 Function, Atul D. Joshi, Nektarios Barabutis, Charalampos Birmpas, Christiana Dimitropoulou, Gagan Thangjam, Mary Cherian-Shaw, John Dennison, John D. Catravas

Bioelectrics Publications

Transendothelial hyperpermeability caused by numerous agonists is dependent on heat shock protein 90 (Hsp90) and leads to endothelial barrier dysfunction (EBD). Inhibition of Hsp90 protects and restores transendothelial permeability. Hyperacetylation of Hsp90, as by inhibitors of histone deacetylase (HDAC), suppresses its chaperone function and mimics the effects of Hsp90 inhibitors. In this study we assessed the role of HDAC in mediating lipopolysaccharide (LPS)-induced transendothelial hyperpermeability and acute lung injury (ALI). We demonstrate that HDAC inhibition protects against LPS-mediated EBD. Inhibition of multiple HDAC by the general inhibitors panobinostat or trichostatin provided protection against LPS-induced transendothelial hyperpermeability, acetylated and suppressed Hsp90 …


The Omega-3 Fatty Acid Docosahexaenoic Acid Attenuates Organic Dust-Induced Airway Inflammation., Tara M. Nordgren, Taylor D. Friemel, Art J. Heires, Jill A. Poole, Todd A. Wyatt, Debra J. Romberger Nov 2014

The Omega-3 Fatty Acid Docosahexaenoic Acid Attenuates Organic Dust-Induced Airway Inflammation., Tara M. Nordgren, Taylor D. Friemel, Art J. Heires, Jill A. Poole, Todd A. Wyatt, Debra J. Romberger

Journal Articles: Pulmonary & Critical Care Med

Workers exposed to organic dusts from concentrated animal feeding operations (CAFOs) are at risk for developing airway inflammatory diseases. Available preventative and therapeutic measures for alleviating dust-induced lung disease are inadequate. Because omega-3 fatty acids can mitigate inflammatory processes, we aimed to determine whether nutritional supplementation with the omega-3 fatty acid docosahexaenoic acid (DHA) could reduce the airway inflammatory consequences of exposures to organic dust. Aqueous extracts of organic dusts from swine CAFOs (ODE) were utilized. In DHA-pretreated human bronchial epithelial cells, lung fibroblasts, monocyte cell cultures, and precision-cut murine lung slices, we found that DHA pretreatment dose-dependently decreased ODE-induced …


Vascular Ehlers-Danlos Syndrome: A Rare Disorder Presenting With Focal Convulsions, Shakeel Ahmed, Syed Rehan Ali, Naila Nadeem, Muhammad Hamid Nov 2014

Vascular Ehlers-Danlos Syndrome: A Rare Disorder Presenting With Focal Convulsions, Shakeel Ahmed, Syed Rehan Ali, Naila Nadeem, Muhammad Hamid

Department of Paediatrics and Child Health

Vascular Ehlers-Danlos Syndrome (VEDS), previously called Ehlers-Danlos syndrome type-IV, is a heterogeneous group of heritable connective tissue disorders characterized by thin, translucent skin, easy bruising, arterial, intestinal, and/or uterine fragility. There is large vessel involvement that leads to arterial rupture often preceded by aneurysm, arteriovenous fistulae, or dissection. Noninvasive imaging studies such as CT angiography and MR angiography are preferred as diagnostic studies for this condition. We are reporting a 4 years old girl who was presented with right sided unilateral convulsions and hypertension. CT angiogram showed stenosis with post-stenotic dilatation of coeliac and superior mesenteric arteries. There were extensive …


Role Of A Genetic Variant On The 15q25.1 Lung Cancer Susceptibility Locus In Smoking-Associated Nasopharyngeal Carcinoma, Xuemei Ji, Weidong Zhang, Jiang Gui, Xia Fan, Weiwei Zhang, Yafang Li, Guangyu An, Dakai Zhu, Qiang Hu Oct 2014

Role Of A Genetic Variant On The 15q25.1 Lung Cancer Susceptibility Locus In Smoking-Associated Nasopharyngeal Carcinoma, Xuemei Ji, Weidong Zhang, Jiang Gui, Xia Fan, Weiwei Zhang, Yafang Li, Guangyu An, Dakai Zhu, Qiang Hu

Dartmouth Scholarship

Background: The 15q25.1 lung cancer susceptibility locus, containing CHRNA5, could modify lung cancer susceptibility and multiple smoking related phenotypes. However, no studies have investigated the association between CHRNA5 rs3841324, which has been proven to have the highest association with CHRNA5 mRNA expression, and the risk of other smoking-associated cancers, except lung cancer. In the current study we examined the association between rs3841324 and susceptibility to smoking-associated nasopharyngeal carcinoma (NPC).

Methods: In this case-control study we genotyped the CHRNA5 rs3841324 polymorphism with 400 NPC cases and 491 healthy controls who were Han Chinese and frequency-matched by age (±5 years), gender, and …